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During the end of September 1997, an unusual outbreak of severe dehydrating watery diarrhoea cases and deaths were reported from Malda town. Vibrio cholerae 01 El tor, the causative agent responsible for this episode was isolated from 56.5% of cases sampled. Three of the five drinking water samples were also positive for V cholerae 01. Majority of cases were adults. Isolated strains were uniformly resistant to furazolidone and intermediately to norfloxacin. Indiscriminate use of antibiotic should be discouraged for development of multidrug resistant strains.

A bioequivalence study of two oral formulations of 400 mg norfloxacin was carried out in 18 healthy volunteers according to a single dose, two-sequence, cross-over randomized design at College of Pharmacy, King Saud University, Riyadh, Saudi Arabia, jointly with King Khalid University Hospital. The two formulations were: Uroxin (Julphar, United Arab Emirates) as test and Noroxin (Merck Sharpe & Dohme, BV, Netherlands). Both test and reference formulations were administered to each subject after an overnight fasting on 2 treatment days separated by 1 week wash-out period. After dosing, serial blood samples were collected for a period of 24 h. Plasma harvested from blood, was analysed for norfloxacin by a sensitive, reproducible and accurate HPLC method. Various pharmacokinetic parameters including AUC(0-t), AUC(0-infinity), C(max), T(max), T(1/2), and K(el) were determined from plasma concentrations for both the formulations and found to be in good agreement with reported values. AUC(0-t), AUC(0-infinity), and C(max) were tested for bioequivalence after log-transformation of data. No significant difference was found based on ANOVA; 90% confidence interval for test/reference ratio of these parameters were found within a bioequivalence acceptance range of 80-125%. Based on these statistical inferences, it was concluded that Uroxin is bioequivalent to Noroxin.

This work studied the sustained release of ciprofloxacin or norfloxacin and gentamicin from nonstoichiometric hydroxyapatite (nHA) and anionic collagen composite. Within the first 24 and 48 h, the total antibiotic supply was significantly higher than the minimal inhibitory concentration required for the majority of the gram-negative bacteria. Although gentamicin was completely released from the matrix after 48 h by a normal diffusion mechanism, ciprofloxacin or norfloxacin release was characterized by a 2-phase release mechanism due to binding to nHA by complexation with calcium ion. Under the conditions studied, most of the norfloxacin or ciprofloxacin only will be disposable due to bioresorption or dissociation of the complexes. In conclusion, due to its biocompatibility nHA-anionic collagen composite may be a convenient support for the double sustained release of the antibiotics gentamicin and ciprofloxacin/norfloxacin for the control of bone infection while promoting bone tissue growth.

With the aim of promoting the targeting of macrophage mannose receptors and the internalisation of the norfloxacin antibiotic, which is active against some intracellular bacteria, a macromolecular prodrug was synthesised where the antibiotic and mannosyl moieties were coupled to a polymeric carrier, namely poly(L-lysine citramide imide). This carrier, which derived from two metabolites, citric acid and L-lysine, is known to be biocompatible and slowly degradable under slight acidic conditions. Norfloxacin was coupled onto the acid groups present along the polymer chains, and conjugates were characterised by UV, TLC and SEC. The mannosyl groups selected to promote the targeting of the mannose-specific lectin present on the outer membrane of macrophages were incorporated through a biodegradable glycolic spacer arm. Two different strategies were considered to synthesise the full conjugates, namely coupling norfloxacin onto mannosylated conjugates, and coupling mannose onto PLCAI/Nflx conjugates. The second pathway led to better results regarding mannosylation. The presence of norfloxacin and mannose caused chain aggregation, especially for conjugates with a high content of mannosyl residues. The targeting ability of the prodrug was investigated using a method based on the competition between the mannosylated macromolecules and glucose oxidase, a mannosyl-bearing non-human protein. This method showed that prodrug macromolecules competed effectively with glucose oxidase and thus should be able to bring the drug up to the mannosyl receptor-bearing membranes of macrophages infected by intracellular bacteria.

The aim of this study is to evaluate the therapeutic effect of the antimicrobial agents, fosfomycin (FOM), minocycline (MINO), kanamycin (KM) and norfloxacin (NFLX) in the enterohemorrhagic Escherichia coli (EHEC) infected mouse model which we established previously (Infect. Immun. 62 (1994) 3447-3453). Each of the antimicrobial agents, 1/16 LD(50), was given to the mice per os (p.o. ) or intraperitoneally (i.p.) for 3 days after bacterial inoculation and then we observed their mortality rate for 2 weeks. The mortality rates of mice administered with MINO (p.o./i.p.), KM (p.o.), NFLX (p. o./i.p.) were significantly lower than those of the control group. Both the bacterial number and VT2c level in the feces of the FOM group were lower than those of the NFLX group on day 1, but reversed on day 3. In an in vitro experiment, each of the four drugs in combination with mitomycin C (MMC) caused a more significant decrease in the bacterial number than sole MMC, and they consequently indicated the suppressive effect on the release of VT2c.

Antibiotic therapy for infection with Shiga-toxin-producing Escherichia coli O157:H7 is controversial because of the possibility of its inducing hemolytic uremic syndrome and acute encephalopathy. In a previous study, mice with protein-calorie malnutrition were found to be highly susceptible to this pathogen. The efficacy of oral antibiotic therapy in malnourished mice infected with O157 organisms was assessed. Mice fed a low-protein calorie diet were infected intragastrically with 2 x 10(6) colony-forming units of a Shiga-toxin-producing strain of Escherichia coli O157:H7. Infected mice were orally given a therapeutic dose of an antibiotic, including norfloxacin, fosfomycin, kanamycin, ampicillin, clarithromycin or trimethoprim-sulfamethoxazole for 3 days: mice on protocol A received the antibiotic on days 1-3, starting on the day after infection, and mice on protocol B received the antibiotic on days 3-5. The duration of fecal pathogen excretion was shorter and the toxin level in the stool and blood lower in the mice that received protocol A than in untreated mice; all of the mice treated on protocol A survived the lethal infection. All antibiotics except trimethoprim-sulfamethoxazole, administered on protocol B, exhibited the same effect as that exhibited by the respective antibiotic administered on protocol A. Only the mice treated with protocol B of trimethoprim-sulfamethoxazole had a higher toxin level in the blood than untreated controls, resulting in 95% mortality. These results suggest that the antibiotics used in this study, except for trimethoprim-sulfamethoxazole, could reduce the risk of hemolytic uremic syndrome and acute encephalopathy following Escherichia coli O157:H7 infection in humans, and that fosfomycin, in particular, may be relevant for testing in humans.

Single-dose pharmacokinetics of norfloxacin after intravenous administration of norfloxacin nicotinate at 10 mg norfloxacin/kg body weight was investigated in cows with healthy udders and in cows with chronic subclinical and postacute clinical mastitis. An HPLC method was used to determine the norfloxacin concentrations in serum and milk. Significant differences were observed in norfloxacin pharmacokinetics when administered to cows with infected udder quarters. The clearance (Cl) values were 10.4+/-2.5, 13.2+/-1.9 and 14.2+/-2.1 mL/min/kg (mean +/-SD) in the control (healthy udder) cows and in cows with subclinical and postacute clinical mastitis, respectively. There appeared to be a trend of increasing clearance according to severity of the disease. The volume of distribution at steady state (Vss) in the respective groups was 3.1+/-0.7, 2.2+/-0.6 and 1.3+/-0.2 L/kg. The volume of distribution was significantly decreased in the cows with postacute clinical mastitis. The half-lives (t1/2) and mean residence times (MRT) of norfloxacin were 353, 206 and 115 min (harmonic means) and 306+/-76, 168+/-39 and 95+/-9 min in control cows or in cows with subclinical and postacute clinical mastitis, respectively. The half-lives in the clinical mastitis group were significantly shorter than in the control group and the mean residence times were significantly shorter in the two mastitis groups when compared to the control group. Norfloxacin concentrations in milk were extremely high when compared to the respective serum concentrations. The area under the concentration vs. time curve (AUC) of norfloxacin in milk was 23899+/-6206 mg/L x min in the control cow group. The AUC in milk was significantly lower in the infected udder quarters of the mastitis groups (5075+/-1887 mg/L x min and 7484+/-4645 mg/L x min in the subclinical and the clinical group). The AUC values were significantly lower in milk from the infected udder quarters of the cows with chronic subclinical and postacute clinical mastitis when compared to the values in milk from the healthy quarters of the same udder. Norfloxacin was marginally bound to serum protein. The binding was concentration dependent and was 19, 13 and 6% at 0.2, 1.0 and 8.4 mg/L, respectively. Binding to milk protein was 46-51% and concentration independent. An in vitro dialysis model was used to simulate drug transport between serum and milk as a function of protein binding. The results showed that the rate of norfloxacin disposition from milk to serum was slower than from serum to milk, which was in agreement with the findings obtained in the pharmacokinetic study. Norfloxacin was poorly soluble in organic solvents and our results suggest that changes in the degree of ionization of the drug in different body fluids considerably affect its disposition.

In an attempt for better treatment of partial thickness burn wounds topical ointments containing metronidazole and norfloxacin in different bases were prepared and in vitro release was conducted in phosphate buffer pH 6. It was found that, diffusion of the metronidazole and norfloxacin from the lanolin petrolatum base with 0.25% w/w dimethyl sulfoxide was maximum through hairless rat abdominal skin. Antimicrobial activity of different prepared formulations was found to be more effective both against aerobic and anaerobic bacteria than marketed formulation (1% silver sulfadiazine cream USP). Formulations were significantly effective as compared to that of marketed formulation in wound contraction of the partial thickness burn wound. Histopathological reports supported effectiveness of formulations. It was found that 1% metronidazole and 1% norfloxacin ointments are suitable for treating the partial thickness burn wound.

Studies on a combination therapy of fosfomycin (FOM) and norfloxacin (NFLX) against chronic otitis media were performed, and the following results were obtained. 1. The fractional inhibitory concentration index (FIC index) < or = 0.5 between FOM and NFLX showed 66.7% (4/6) against S. aureus isolated from chronic otitis media and 80.5% (4/5) against P. aeruginosa. 2. Clinical effects was excellent in 2 cases (18.2%), good in 6 cases (54.5%) and poor in 3 cases (27.3%). 3. Bacteriologically 9 strains out of 11 patients were eradicated after the combination treatment; 5/6 in S. aureus and 4/5 in P. aeruginosa. 4. No adverse effect and abnormal laboratory findings were observed in this study. It is suggested that the combination of FOM otic solution and NFLX is useful for the treatment of chronic otitis media.

Background: A prospective study was undertaken to determine the transcorneal penetration of three topically applied fluoroquinolones into aqueous humor., Methods: Cataract patients (n = 224) preoperatively received topically applied gyrase inhibitors (0.3% ciprofloxacin, 0.3% norfloxacin, 0.3% ofloxacin) in two different application modes. In application mode I, patients received on the day before operation 3 x 1 eye drop at 2-h intervals, and on the day of operation 3 drops at 1-h intervals. In application mode II, patients received 9 drops at 15-min intervals on the day of operation only. Just before cataract surgery 50-100 ml aqueous humor was aspirated and stored at -80 degrees C. The HPLC method was used for measuring the concentration., Results: The highest concentrations of all tested antibiotics were measured after the mode of application in which one drop was given every 15 min between 06:00 and 08:00 hours before operation. In this mode, ciprofloxacin achieved a mean aqueous level of 379.8 +/- 327.8 mg/l (range 33-1388 mg/l), norfloxacin 182.1 +/- 118.1 mg/l (range 38-480 mg/l) and ofloxacin 563.9 +/- 372.1 mg/l (range 64-1455 mg/l). These mean concentration are all above the MIC90 of gram-negative bacteria like Proteus mirabilis and Escherichia coli. In some cases the concentrations of ciprofloxacin and ofloxacin, but never norfloxacin, reached therapeutic values above the MIC90 of Staphylococcus aureus and Staphylococcus epidermidis., Conclusions: The mean concentration value of 0.3% ciprofloxacin and of 0.3% ofloxacin in the aqueous humor reached the MIC90 values of the frequently occurring gram-positive and gram-negative bacteria. Of the currently available topical fluoroquinolones, ofloxacin achieved the highest aqueous humor concentration. Considering the higher antimicrobial activity of ciprofloxacin, both ciprofloxacin and ofloxacin may be useful ophthalmic agents in antibacterial management, but they are not efficient against Streptococcus pneumoniae and Pseudomonas aeruginosa.

A new pH-sensitive polymer, P-4135F, was evaluated as a colon delivery device for norfloxacine (NFLX) which is used for the therapy of patients with Vero toxin-producing Escherichia coli gastroenteritis. P-4135F has a dissolution threshold pH of 7.2 which is higher than the conventional pH-sensitive polymers, Eudragit S100 and L100. To compare the dissolution site of P-4135F coated tablets with other enteric polymer coatings, mini-tablets containing sodium fluorescein (FL) as a model drug were prepared by coating them with the three polymers. After oral administration of FL mini-tablets to rats, the first-appearance time, Ti, of FL into the systemic circulation was measured. The Tis were 0.7+/-0.2 h for Eudragit L100, 1.8+/-0.4 h for S100 and 2.0+/-0.3 h for P-4135F. Direct inspection of the dissolution process of the FL mini-tablets after oral administration to rats was performed by abdominal incision studies. All of the coated FL mini-tablets started to dissolve in the rat ileum. The dissolution sites were identified to be proximal to the ileocecal junction for P-4135F, at the middle part of the ileum for Eudragit S100 and at the proximal part of the ileum for Eudragit L100. NFLX tablets with different membrane thicknesses of P-4135F were prepared and were orally administered to beagle dogs. The colon delivery efficiency was evaluated by measuring the Ti of NFLX into the systemic circulation. The mean Tis were 1.33+/-0.33 h for 56.8+/-0.5 microm membranes, 3.75+/-0.25 h for 64.6+/-0.7 microm membranes, 4.00+/-1.00 h for 70.5+/-0.5 microm membranes and 3.00+/-1.00 h for 74.9+/-0.4 microm membranes. By comparing the Ti, 4.33+/-0.33 h, obtained after oral administration of NFLX in a pressure-controlled colon delivery capsule, and the colon arrival time, 3.5+/-0.3 h, determined by a sulfasalazine test in beagle dogs. P-4135F coated NFLX tablets appeared to dissolve and disintegrate before reaching the colon. Studies using rats and beagle dogs have suggested that P-4135F dissolves in the lower part of the small intestine, i.e., the ileum. These studies also suggest that this new polymer will be useful for the delivery of NFLX to the lower part of the small intestine.

Objective: Selective intestinal decontamination with norfloxacin is useful in the prevention of bacterial infections in cirrhotic patients with gastrointestinal bleeding. However, bleeding cirrhotic patients with ascites, encephalopathy, or shock are at high risk to develop bacterial infections in spite of prophylactic norfloxacin. The aim of this study was to assess whether the addition of intravenous ceftriaxone could improve the efficacy of prophylaxis with norfloxacin in these patients., Methods: Fifty-six cirrhotic patients with gastrointestinal hemorrhage and ascites, encephalopathy, or shock were randomized into two groups: Group 1 (n = 28) received oral norfloxacin 400 mg/12 h for 7 days, and group 2 (n = 28) received norfloxacin plus intravenous ceftriaxone 2 g daily during the first 3 days of admission., Results: Ten patients were excluded because of community-acquired infection, surgery, or death within the first 24 h. The incidence of bacterial infections during hospitalization was 18.1% in group 1 and 12.5% in group 2 (p = NS). The incidence of severe infections (spontaneous bacterial peritonitis, bacteremia, or pneumonia) was also similar in both groups: 9% in group 1 versus 8.3% in group 2 (p = NS). There were no statistical differences between the two groups with respect to duration of hospitalization or mortality. The cost of antibiotic therapy (including prophylaxis and treatment of infections) was significantly higher in group 2., Conclusion: These results suggest that the addition of intravenous ceftriaxone during the first 3 days of hospitalization does not improve the cost-efficacy of oral norfloxacin in the prevention of bacterial infections in cirrhotic patients with gastrointestinal bleeding and high risk of infection.

In view of the very great efficacy of 3rd generation cephalosporins and fluoroquinolones used as monotherapy in the treatment of uncomplicated acute pyelonephritis, the addition of an aminoglycoside is not currently recommended, because of the unfavourable balance of the advantages and disadvantages of this antibiotic class. However, a brief course of aminoglycosides may nevertheless be useful during the initial phase of treatment, especially in hospitalised subjects. The authors analyse the contribution of three recently published studies to this debate.

The pharmacokinetics and tissue distribution of two norfloxacin (NFLX) formulations, norfloxacin-glycine acetate (NFLXGA) and norfloxacin nicotinate (NFLXN), were compared after single oral administration with a dose of 5 mg equivalent NFLX base/kg of body weight in twenty rabbits. The pharmacokinetic characteristics of all formulations were fitted by a two-compartment open model. The elimination half-life (T1/2beta) of NFLX (3.37+/-1.37 hr) was not significant as compared with those of NFLXN (3.61+/-0.65 hr) and NFLXGA (3.93+/-1.54 hr). The absolute bioavailability (F) of NFLX, NFLXN and NFLXGA was calculated as 29%, 45% and 40%. In addition, tissue distribution of NFLXN and NFLXGA did not show any differences of NFLX concentrations in liver, kidney, serum and muscle. From the present results, it could be suggested that NFLXN and NFLXGA are considered to be bioequivalent when they use oral medication for rabbits.

Norfloxacin 400 mg twice-a-day has proven to be effective and safe in the treatment of uncomplicated urinary tract infections (UTI). Since previous pharmacokinetic studies demonstrate the feasibility of using norfloxacin 800 mg once-daily, and this scheme is assumed to improve patient compliance, a double-blind randomized clinical trial was performed to compare the efficacy and safety of norfloxacin 800 mg once-daily (Group A) versus norfloxacin 400 mg twice-daily (Group B) in the treatment of adult female UTI for a 7-10 day period. Eighty-six adult women with clinical symptoms and urinary sediment signs suggestive of UTI were enrolled. In Group A, treatment was clinically assessed as effective in 95.3% and bacteriologically effective in 92.0% of the patients. In Group B, clinical and bacteriological efficacy was 100% and 95.5%, respectively. Differences between groups are not statistically significant. Adverse events were reported by 14.0% of patients in Group A and 9.6% in Group B (difference not statistically significant). There was one withdrawal due to dizziness. In this study, norfloxacin 800 mg once-a-day was as effective and safe as norfloxacin 400 mg twice-a-day in the treatment of uncomplicated urinary tract infections in women.

In an open, randomised monocentric crossover study in six male and six female healthy volunteers, the urinary antibacterial activity and pharmacokinetics of enoxacin, norfloxacin and ciprofloxacin were assessed. Urine was collected up to 6 days, and venous blood samples up to 12 h, after a single oral dose of 400 mg enoxacin, 400 mg norfloxacin and 500 mg ciprofloxacin. Enoxacin (250 mg/l) demonstrated the highest peak concentration (median) in the urine (0-6 h), followed by ciprofloxacin (237 mg/l) and norfloxacin (157 mg/l) as determined by the HPLC assay. The total amount (mean) excreted by the kidneys as parent drugs were as follows: enoxacin 54% of dose, ciprofloxacin 33% of dose, and norfloxacin 22% of dose. The mean plasma concentrations decreased from 1 to 4 h after administration for enoxacin from 1.9 to 1.4 mg/l, for ciprofloxacin from 2.0 to 0.8 mg/l and for norfloxacin from 1.3 to 0.5 mg/l. The antibacterial activity in urine was determined as urinary bactericidal titers (UBT), i.e. the highest 2-fold dilution of urine still bactericidal for the reference organism (E. coli ATCC 25,922) and for five uropathogens with minimal inhibitory (MIC) and bactericidal (MBC) concentrations ranging from highly susceptible to resistant cultured from the urine of patients with complicated urinary tract infections (UTI). For the E. coli ATCC 25,922, the organism with the lowest MIC, median UBTs of ciprofloxacin were present for 4 days, decreasing from 1:512 to 1:2, that of enoxacin for 2 days, decreasing from 1:256 to 1:4, and that of norfloxacin for 2 days, decreasing from 1:128 to 1:2. For the five uropathogens (with increasing MICs: K. pneumoniae, P. mirabilis, E. coli (resistant to nalidixic acid), P. aeruginosa and E. faecalis), the UBTs decreased in general, according to MICs, demonstrating the same relations of UBTs for ciprofloxacin (highest) versus enoxacin (medium) versus norfloxacin (lowest) with one exception (P. mirabilis) for which norfloxacin showed higher UBTs than enoxacin. The minimal urinary bactericidal concentrations (MUBC), as derived from urinary concentrations, and UBTs showed a fairly wide inter- and intraindividual range and were generally higher than the corresponding MBCs as determined in Mueller Hinton broth. In conclusion, according to antibacterial activity in urine determined as UBTs, a single oral dose of ciprofloxacin (500 mg) generally resulted in the highest and longest-lasting UBTs followed by that of enoxacin (400 mg) and norfloxacin (400 mg). A dose of 400 mg enoxacin can be expected to be at least equivalent if not superior to that of 400 mg norfloxacin. Only enoxacin and ciprofloxacin exhibited urinary bactericidal activity against all test organisms up to 12 h in all individuals. Therefore, clinical comparison of enoxacin versus ciprofloxacin in the treatment of complicated UTI could be worth testing.

The use of fluorinated quinolones for prophylaxis of infections in neutropenic cancer patients has led to a reduction of infections with gram-negative enteric bacilli, but there is concern about the emergence of antibiotic-resistant entero-bacterial infections and a rise of gram-positive bacteremias. Due to these concerns, in mid-1995 the use of prophylactic norfloxacin was discontinued in our unit. In order to evaluate the impact of this measure on the infectious morbidity in our unit, 91 severe neutropenic episodes in 58 patients with hematologic malignancies who did not receive norfloxacin prophylaxis (NO group) were closely matched to 91 episodes in 60 patients who received norfloxacin prophylaxis (NORFLO group). There were no differences in the incidence of febrile neutropenia, fever of unknown origin or bacteremia during the first febrile episode. There was a trend for a higher rate of coagulase-negative staphylococcal bacteremia in the NORFLO group (5 vs. 11 cases in the NO and NORFLO groups, respectively, p = NS). Enterobacterial bloodstream infections were more frequent in the NO group (13 vs. 2 cases, respectively, p = 0.01), especially Escherichia coli (9 vs. 1 case, respectively, p = 0.01). Twelve of 13 enterobacterial isolates in the NO group were sensitive to the fluoroquinolones vs. 0/2 in the NORFLO group (p = 0.07). We conclude that the abrupt discontinuation of norfloxacin prophylaxis in our ward led to a rapid increase in the rate of fluoroquinolone-susceptible enterobacterial infections, with a scarce impact on infectious morbidity. This suggests that the selection of resistant flora in an inpatient ward by prophylactic antimicrobials may be reversible following the discontinuation of the prophylactic agent(s).

The pharmacokinetics of norfloxacin after intravenous (i.v.) and oral (PO) administration in lambs (n = 5) and adult sheep (n = 5) were studied. After i.v. administration (10 mg.kg-1) plasma concentrations were best fitted by a three-compartment open model in both age groups. Distribution volumes were significantly larger in lambs (approximate 4.0 fold difference between 4 week old and adult sheep). There was no significant difference (p < 0.05) between the groups in terms of elimination halflife but plasma clearance was significantly higher in lambs. Norfloxacin was poorly absorbed after oral administration (60 mg.kg-1) in sheep (F = 4.04%). Mean oral bioavailability was 73.51% in lambs (30 mg.kg-1). Norfloxacin elimination was faster in lambs after oral administration. MRTt was significantly prolonged in both age groups when compared with the respective data for i.v. administration.

An outbreak of O-157:H7 diarrheal illnesses occurred in junior schools of Sakai-city, Osaka prefecture, in last July, 1996. At the beginning of the outbreak, many patients rushed to outpatient clinics. From the practical experiences, we examined the necessity of fluid therapy in patients regarding their initial clinical features. The risk factors for development of HUS were noted as presence of fever, WBC counts of more than 10,000/microliter and more than 1.0 mg/dl of CRP. During the prodoromal illness, administration with available antimicrobial agents would be advisable for high risk patients, while it would yet be remain to be further investigated. The majority of the patients with clinical manifestations showed neither signs for dehydration nor electrolyte abnormalities based on the blood examination data and biochemical analysis of the serum. Therefore, the fluid therapy did not appear necessary for majority of patients except a few high risk patients, when outpatient clinics were crowded with emergency patients.

This study was undertaken to compare aqueous humor penetration of topical 0.3% ciprofloxacin, 0.3% norfloxacin and 0.3% ofloxacin in 63 patients undergoing cataract surgery. The patients were divided into two groups. Group 1 (long-term treatment) involved 30 patients undergoing cataract extraction who received either 0.3% ciprofloxacin, 0.3% norfloxacin or 0.3% ofloxacin topical drops. Each patient was preoperatively given a single drop per hour six times. At the time of surgery, 0.1 ml aqueous fluid was aspirated from the anterior chamber and immediately stored at -70 degrees C. Topically applied ciprofloxacin, ofloxacin and norfloxacin achieved mean aqueous humor levels of 2.80 +/- 1.07, 2.95 +/- 1.19 and 1.50 +/- 0.48 micrograms/ml respectively. There was no statistically significant difference in intraocular mean aqueous levels of ciprofloxacin versus ofloxacin. Topical ciprofloxacin and ofloxacin achieved mean aqueous humor levels significantly higher than norfloxacin (p < 0.001 and p < 0.0008 respectively). Group 2 (short-term treatment) involved 33 patients undergoing cataract extraction who received 0.3% ciprofloxacin, 0.3% ofloxacin and 0.3% norfloxacin topical drops. These patients were given one drop at 90 minutes and one drop 30 minutes preoperatively. At the time of surgery, 0.1 ml aqueous fluid was aspirated from the anterior chamber and immediately stored at -70 degrees C. Topically applied ciprofloxacin, ofloxacin and norfloxacin achieved mean aqueous humor levels of 1.11 +/- 0.50, 1.50 +/- 0.62 and 1.20 +/- 0.43 micrograms/ml respectively. There was no statistically significant difference in intraocular mean aqueous humor levels of ofloxacin versus norfloxacin and ciprofloxacin versus norfloxacin. Topical ofloxacin achieved a significantly higher mean aqueous humor level than ciprofloxacin (p < 0.03). All levels were above the minimum inhibitory concentrations of ciprofloxacin, ofloxacin and norfloxacin for most of the sensitive organisms.

The tear pharmacokinetic profiles of 0.3% ciprofloxacin, 0.3% ofloxacin, and 0.3% norfloxacin ophthalmic solutions after a single drop topically administrations in the eyes of 30 healthy volunteers were evaluated. Tear samples collected at 30, 120, 180, and 240 minutes, were analyzed for drug concentrations by high performance liquid chromatography (HPLC) with fluorometric detection. Topically applied ciprofloxacin, ofloxacin, and norfloxacin achieved the mean tear concentrations (mean +/- SD) of 11.28 +/- 6.98, 6.52 +/- 4.06, and 13.28 +/- 8.78 micrograms/g at 30 min, and then fell to 3.52 +/- 1.30, 4.82 +/- 1.80, and 5.79 +/- 4.80 micrograms/g at 240 min, respectively. Topical norfloxacin achieved mean tear level significantly higher than ofloxacin at 30 min (p = 0.031). There were no statistically significant differences in the mean tear levels of ciprofloxacin versus ofloxacin (at 30, 120, 180, and 240 min), ciprofloxacin versus norfloxacin (at 30, 120, 180, and 240 min) and ofloxacin versus norfloxacin (at 120, 180, and 240 min). However, the mean tear levels, 240 min after dosing ciprofloxacin and norfloxacin, fell to the statistically significant concentrations (p = 0.02 and p = 0.01, respectively). But, it is concluded that concentrations of ciprofloxacin, ofloxacin, and norfloxacin in tears were still significantly greater than the minimum inhibitory concentrations for the most sensitive organisms, 240 min after a single drop application.

In an open randomised crossover study the antibacterial activity of pefloxacin and norfloxacin was assessed in the urine after a single 800-mg oral dose in 14 healthy female volunteers. Pefloxacin demonstrated lower peak concentrations in the urine than norfloxacin (mean, 217.2 mg/l versus 492.9 mg/l as determined by the microbiological assay) but pefloxacin was present over a longer period of time in sufficient concentrations than norfloxacin. Mean urine levels of at least 2 mg/l were present for 7 days after pefloxacin administration and 2 days after norfloxacin administration as determined by the microbiological assay. Overall, the urinary recovery of pefloxacin and norfloxacin amounted to 49.3% and 25.1%, respectively, of the total administered dose. The average urine bactericidal activity against the five test organisms was as follows: against reference strain Escherichia coli ATCC 25922 susceptible to nalidixic acid (Nal-S) for 5 days with pefloxacin and 2 days with norfloxacin; against three clinical isolates, one strain each of E. coli resistant to nalidixic acid (Nal-R), Klebsiella pneumoniae Nal-R, and Staphylococcus saprophyticus, for 3 days with pefloxacin and 24 h with norfloxacin; and against a clinical isolate of Enterococcus faecalis for 2 days with pefloxacin and 12 h with norfloxacin. In conclusion, pefloxacin as a single dose proved to have sufficiently high and long-lasting urine bactericidal activity against urinary pathogens. These findings support the results of a meta-analysis of seven clinical trials in patients with uncomplicated lower UTI, demonstrating a single oral dose of 800 mg pefloxacin to be as effective as a conventional treatment with comparative drugs.

An attempt has been made to design suitable niosome-encapsulated drug delivery system for ciprofloxacin and norfloxacin. Encapsulation of ciprofloxacin and norfloxacin in niosomes was investigated and the nasal and intestinal absorption of the products studied. More than 80% of the drugs were successfully encapsulated to give products with sustained release characteristics. Encapsulation in niosomes also improved the stability of the antibacterial compounds. Although the systemic availability of these niosome-encapsulated antibacterial compounds was not increased after nasal administration, intestinal absorption was significantly higher in comparison with that of plain inclusion complexes.

Objective: A prospective study was undertaken to determine the transcorneal penetration of three topically applied fluoroquinolones into aqueous humour., Methods: Two hundred and twenty-four patients undergoing cataract extraction received 0.3% ciprofloxacin, norfloxacin or ofloxacin eye drops by two different administration modes with different frequencies and intervals of application. At the beginning of cataract extraction (0.5-3 h after the last drop), 50-100 microliters aqueous fluid was aspirated from the anterior chamber and immediately stored at -80 degrees C. Antibiotic concentrations were measured using high-performance liquid chromatography., Results: Generally, topical ofloxacin and ciprofloxacin yielded aqueous humour levels higher than topical norfloxacin. The highest concentrations of all tested fluoroquinolones were measured after using an application mode, in which one drop was given every 15 min between 0600 hours and 0800 hours, prior to operation. When applied by this mode, ciprofloxacin achieved a mean aqueous level of 0.380 (+/- 0.328) microgram.ml-1 (range 0.033-1.388 micrograms.ml-1), norfloxacin 0.182 (0.118) microgram.ml-1 (range 0.038-0.480 microgram.ml-1) and ofloxacin 0.564 (0.372) microgram.ml-1 (range 0.064-1.455 micrograms.ml-1). These mean concentrations were above the minimum inhibitory concentration (MIC90), concentrations required for inhibition of 90% of pathogen strains in vitro of gram-negative bacteria, such as Proteus mirabilis and Escherichia coli. Therapeutic values above the MIC90 of Staphylococcus epidermidis, the pathogen causing eye infections most frequently, were reached by 67.5% of patients after ofloxacin and by 41% after ciprofloxacin, but never after norfloxacin treatment., Conclusion: Of the currently available topical fluoroquinolones, ofloxacin achieved the highest aqueous humour concentration. This fluoroquinolone may be an useful ophthalmic agent for topical antibacterial management, but it does not seem to be prophylactically effective against Streptococcus pneumoniae or Pseudomanas aeruginosa.

The effectiveness of norfloxacin as an antibacterial agent in ophthalmology is limited by poor drug delivery and limited ocular bioavailability. Liposomes containing norfloxacin have been prepared from different phospholipids using a novel technique with an encapsulation efficiency sixteen times greater than that of a conventional film method. The in-vitro release of the norfloxacin and the transcorneal characteristics of the liposomes have been evaluated. Differential scanning calorimetry was used to determine the interaction occurring between liposomes and cornea. The release of liposome-entrapped norfloxacin was affected by the pH of the environment. In the in-vitro corneal perfusion studies, norfloxacin-loaded liposome was transferred through the cornea at a slower rate than was the free drug. Norfloxacin-loaded liposomes were accumulated primarily in the cornea. The drug corneal retention of the lipids increased in the order dimyristoyl-L-alpha-phosphatidylcholine < dipalmitoyl-L-alpha -phosphatidylcholine < distearoyl-L-alpha-phosphatidylcholine. In the corneal drug-elimination study, liposomal norfloxacin increased the loading of the drug in cornea; the maximum value of the loading occurred 5 h after dosing. The drainage of liposomes from the cornea was somewhat slower than the solution form. Accumulation of norfloxacin in the cornea was greater for the liposome-entrapped drug. The results suggest that norfloxacin-loaded liposomes are absorbed by the cornea via endocytosis.

The formation constants of the fluoroquinolones norfloxacin and ciprofloxacin with Mg2+ (log beta 1 = 2.97(4), log beta 2 = 5.6(2)), Zn2+ (log beta 1 = 3.77(2), log beta 2 = 7.59(3)), and Fe2+ (log beta 1 = 3.99(5), log beta 2 = 7.2(5)) were determined by potentiometric titration. The pH at which precipitation occurred in the titration solutions was compared for the metal ions Ca2+, Mg2+, Zn2+, Fe2+, Cu2+, and Al3+. The formation constants were used to predict a rank order of metals that may be expected to hinder the gastrointestinal absorption of the fluoroquinolones, in vivo. The effects of metal ions on the pharmacokinetics of orally-administered norfloxacin in the dog were investigated. Norfloxacin (12 mg/kg) was administered alone or with equimolar doses of each of the chloride salts of Ca2+, Mg2+, Zn2+, Fe2+, and Al3+. Statistically significant reductions in serum norfloxacin concentrations were observed after analysis by HPLC. The Cmax was reduced 29-85%, while the area under the norfloxacin serum concentration-time curve (AUC0-infinity) was reduced by 29-79%. The extent of the reduction in AUC0-infinity was correlated with the magnitude of the formation constant of the 1:1 norfloxacin:metal chelate complex for the divalent metal ions. On coadministration of 12 mg/kg norfloxacin with various doses of Mg2+ (chloride) the AUC0-infinity and Cmax decreased with increasing Mg2+ dose. The interaction peaked at a Mg2+:norfloxacin ratio of 1:2 suggesting the formation of a 1:2 Mg:norfloxacin complex. Formation constant data were used to simulate the percentage of norfloxacin complexed at pH 6.5. Combinations of metal ion and norfloxacin which result in only a small extent (< 20%) of norfloxacin complex formation can result in relatively large decreases in oral bioavailability of this antimicrobial agent.

The efficacy and safety of ciprofloxacin ophthalmic solution 0.3% and norfloxacin ophthalmic solution 0.3% in the treatment of bacterial conjunctivitis and blepharitis were compared in a double masked randomised study. A total of 131 patients, 65 treated with ciprofloxacin (42 with conjunctivitis and 23 with blepharitis) and 66 treated with norfloxacin (39 with conjunctivitis and 27 with blepharitis) were enrolled in the study at five centres in France. In the efficacy population, pathogens were eradicated or reduced in 96% (24/25) of patients in the ciprofloxacin group and 89% (24/27) in the norfloxacin group. There was no difference between treatments with regard to eradication of particular pathogens. In the efficacy population, clinical cure or improvement was seen in 96% of the patients (24/25 in the ciprofloxacin group and 26/27 in the norfloxacin group). There were no significant differences between ciprofloxacin and norfloxacin with respect to improvements in four symptoms or ten clinical signs. No serious treatment-related adverse events were reported and both ciprofloxacin and norfloxacin were well tolerated.

The use of monodose (800 mg) per os of Norfloxacin was evaluated in 32 patients with cholera at Salvador Mazza's Hospital, Salta, Argentina. It was considered the celerity in negativization of stool culture (100% of cases: 12 hours post administration), it efficiency along time (24/24 controlled patients were negative at 10th day) and MIC of isolated strains (100% of strains were sensitive: range 0.008 to 0.016 micrograms/ml). It was included oral administration of sorbitol 70% in peanut oil in order to study patients at 10th day's control. This method could be an alternative one in the study of asymptomatic carrier. Norfloxacin monodose shows good performance in early negativization of stool culture and it was also effective along the whole observation period, suggesting it could prevent carriage.

The pharmacokinetics of norfloxacin nicotinate were investigated in unweaned and weaned calves. Following intravenous administration of 7.5 and 15 mg/kg (calculated as norfloxacin base) the clearance values were 8.5 +/- 2.0 or 7.7 +/- 1.2 mL/min.kg (unweaned calves) and 11.7 +/- 3.2 or 16.1 +/- 3.3 mL/min.kg (weaned calves). Norfloxacin mean residence time and volume of distribution values were 211 +/- 33 or 227 +/- 41 min (unweaned calves) and 185 +/- 79 or 128 +/- 18 minutes (weaned calves), and 1.8 +/- 0.3 or 1.7 +/- 0.1 L/kg (unweaned calves) and 2.0 +/- 0.7 or 2.1 +/- 0.7 L/kg (weaned calves) following administration of the lower and higher dose, respectively. These results indicated that norfloxacin pharmacokinetics were similar at a dose range of 7.5-15 mg/kg. However, a significant difference was observed in clearance, mean residence time and the half-life values between the unweaned and weaned calves. The only major pharmacokinetic parameter which did not show a significant difference between the investigated groups was the volume of distribution. The pharmacokinetic differences between the non-ruminating (unweaned) and ruminating (weaned) animals seemed to result from changes in drug clearance. The absorption rate after intramuscular administration appeared to change as a result of dose increase. Norfloxacin bioavailability following intramuscular administration ranged from 73 to 106%. The results suggested that larger injection volumes may reduce the extent of absorption.

The efficacy and safety of rufloxacin (400 mg, single dose) were compared to those of norfloxacin (400 mg twice a day for 3 days) for the treatment of women with uncomplicated cystitis. In addition, urine levels, drug level/MIC ratio, and urine antibacterial activity 72 to 84 h after treatment initiation were determined in a subgroup of patients for pharmacodynamic assessment. A total of 203 women were included and treated in this open, randomized clinical trial; 100 patients received norfloxacin, whereas 103 received rufloxacin. Of these, 156 (74 and 82 patients in the norfloxacin and rufloxacin groups, respectively) were considered bacteriologically evaluable. At the first follow-up visits (3 to 12 days after starting the treatment), bacteriological cure rates were 99 and 94% for norfloxacin and rufloxacin, respectively. Seventy-nine percent (119 of 150) of bacteriologically cured patients attended a long-term follow-up visit (4 to 6 weeks after starting the treatment), where a relapse rate of 4% (2 of 54) and 5% (3 of 64) were found in the norfloxacin and rufloxacin groups, respectively. The pharmacodynamic evaluation performed in 35 patients showed similar median urine levels (approximately equal to 25 micrograms/ml) and urine antibacterial activity for both treatment groups against initial isolates, despite a higher norfloxacin level/MIC ratio due to the lower MIC of norfloxacin. Twenty-one patients (20%) in the rufloxacin group and 12 patients (12%) in the norfloxacin group reported 39 and 16 adverse events, respectively, almost all of them being mild and lasting < 24 h. Overall, gastrointestinal reactions were the most frequent adverse events reported. However, 12 patients treated with rufloxacin reported 15 central nervous system adverse events. This study shows that single doses of rufloxacin are as effective as a norfloxacin 3-day standard treatment in uncomplicated cystitis. The results obtained with rufloxacin are consistent with its pharmacodynamic properties.

In a controlled, randomized, double-blind study, 100 patients (66 women, 34 men; age 18-69 years) with acute salmonellosis were treated with norfloxacin (400 mg) or placebo tablets twice daily for 10 days to compare the effects on the excretion time of salmonella bacteria. In all patients salmonellae were detected in the stools before the start of treatment. The follow-up included 6 stool cultures after the start of treatment: day 3-4, day 12-14, and 4 times during 1-6 months. At 3-4 days there were 98% non-excretors in the norfloxacin group (46/47 patients) compared to 38% (17/45) in the placebo group (p < 0.001). The cumulative 6-month elimination rate in norfloxacin patients at 3-4 days was 72%, which was significantly (p = 0.0001) greater than the 31% in the placebo patients. However, there was no significant difference in the proportion of non-excretors or the elimination rate between the 2 groups at the following visits. Only one patient had an adverse event resulting in discontinuation of the treatment. We conclude that norfloxacin treatment for 10 days decreased the excretion of salmonella bacteria during the first week, but there was no difference in excretion rates 1-6 months after treatment initiation in the treatment versus placebo group.

Transrectal ultrasound-guided biopsies of the prostate were performed on 347 consecutive men. All patients were given prophylactic antibiotics. The first 199 patients received 400 mg norfloxacin immediately after the biopsies were performed and 400 mg the same evening. The second group of 148 patients received 400 mg of norfloxacin 1 h before the examination followed by five doses administered twice daily. A total of 15 major complications were noted. In the first group the complication rate was 6.5% and in the second group 1.4%. The different regimes of prophylactic antibiotic treatment were the only parameters shown to have a statistically significant impact on the complication rate. The number of complications decreased, but were not eliminated, when prophylactic treatment with norfloxacin was given before the biopsies were taken and continued for a total of 3 days.

This experimental study examines the development and validation of a new method to evaluate the dissolution rate of norfloxacin tablets. The volume of dissolution medium used here is 100 ml. instead of the 750-900 ml used in the official methods. This smaller volume is closer to that in the human gastric tract. Our main aim is to validate a device which, requiring small volumes of medium, allows the addition of therapeutic amounts of antacids or other substances for in vitro interaction dissolution studies.

Preparation of the fatty alcohol propylene glycol (FAPG) ointment base plays an important role in controlling the physicochemical properties of ointments. These essay investigates the effects of preparative conditions such as cooling rate and stirring rate on the percutaneous absorption of norfloxacin from FAPG ointment. The influence of process-induced variation in enhancing effect of stearic acid which was incorporated into FAPG base was evaluated in vitro on rat skin. In the permeation experiment, norfloxacin penetration significantly increased with faster cooling rate. This result directly related to the increasing norfloxacin skin--vehicle partition coefficient. Histological analysis results showed no appreciable exfoliation of the stratum corneum. The differential scanning calorimetry (DSC) results show that stearic acid enriched lipid in the stratum corneum resulting from treatment with supercooling products may result in more crystalline structure and, hence preferential partitioning of the norfloxacin into the more crystalline regions of the membrane can be observed. A much greater enhancing effect can be achieved when we use stearic acid together with norfloxacin in propylene glycol (PG); but such effect cannot be found if 5 wt% stearic acid/PG suspension is used to pretreat skin before the application of norfloxacin PG solution.

Selective bowel decontamination with the orally administered quinolone antibiotic, norfloxacin, has been shown to suppress gut gram-negative bacteria and help prevent gram-negative infections in cirrhotic patients who are at high risk of bacterial infection. Because this drug does not eradicate gram-positive organisms, it is conceivable that gram-positives could replace the suppressed gram-negatives in the gut and lead to subsequent infection. Also the effect of norfloxacin on translocation (as defined by culture positivity of mesenteric lymph nodes) has received little attention. In this study, the effect of oral norfloxacin on translocation, bacterial peritonitis, and survival was investigated in an animal model of carbon tetrachloride-induced cirrhosis and ascites. Treated rats received daily doses of orally administered norfloxacin from the onset of cirrhosis until they died or were killed. Controls received no antibiotic. Norfloxacin led to a reduction in bacterial peritonitis from 70% in untreated cirrhotic controls to 28% in treated cirrhotic rats; these data were statistically significant (P = .012). There was no effect on overall translocation rate (28% with norfloxacin vs. 50% without norfloxacin) (P > .1). Gram-positives were isolated in 100% of the bacterial peritonitis episodes and in 71.4% of culture-positive mesenteric lymph nodes in treated animals compared with only 25% of peritonitis episodes and 10% of culture-positive mesenteric lymph nodes of untreated cirrhotic controls (P < .01 for peritonitis and P < .05 for translocation). The survival rate was not different between groups (P > .1).(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment with pivalic acid containing prodrugs has been shown to cause carnitine depletion by loss of pivaloyl carnitine in urine. A 7-day standard pivmecillinam treatment of adults lead to a marked decrease of the free serum carnitine concentration (44.6 to 12.9 mumol/liter), whereas no change was seen in those given norfloxacine (40.0 to 40.5 mumol/liter). In some patients irrespective of age the free serum carnitine concentration was decreased to levels (around 10 mumol/liter) at which an impaired ketone-body production may occur. Therefore, there is reason for cautious use of this type of drug irrespective of the age of the patients.

Twelve adult healthy volunteers participated on two occasions in a cross-over study with an interval of 30 days. The bioavailability of norfloxacin 400 mg administered as single oral dose was compared in an Indian preparation A (Torrent) and imported preparation B (Merck Sharp and Dohme (MSD), USA). Plasma was separated from the blood and stored at -20 degrees C for analysis by High Performance Liquid Chromatography. Time taken to achieve mean peak plasma concentration (Tmax) was 2.00 +/- 0.74 hours in case of Torrent (A) and 1.70 +/- 0.49 hours in case of Merck Sharp and Dohme, USA (B). The maximum plasma concentration (Cmax) ranged from 1.60 to 2.87 ug/ml in Torrent (A) and 1.18 to 2.28 ug/ml in case of MSD (B). Area under plasma concentration curve (AUCO-12hr) was 12.70 +/- 3.2 ug/ml/hour for 'A' and 14.80 +/- 2.80 ug/ml/hr for 'B'. Elimination half life (t1/2) for Torrent (A) was 9.25 +/- 5.10 hours and for MSD (B) it was 12.05 +/- 1.05 hours. There was no significant difference in the pharmacokinetic parameters between the two brands (Student's 't' test). Increased elimination half life and large bioavailability (AUC) with both the preparations in the present study suggest the need to be cautious while treating patients with renal problems and to use lower doses in Indian population to achieve desirable kinetics of norfloxacin.

Thirty-four elderly inpatients with long-term urethral catheters were randomly assigned to receive either norfloxacin (200 mg/day) or placebo in a double-blind study with cross-over after three months. Twenty-three patients completed the entire study. Norfloxacin treatment was associated with a persistent decrease in gram-negative isolates (p < 0.005) and the acquisition of gram-positive norfloxacin-resistant flora. It also resulted in a highly statistically significant reduction of symptomatic urinary tract infections (1 vs. 12, p < 0.02), a decrease in catheter-associated local complications, obstructions and leakage (p < 0.05) and an improvement in the patients' general condition (p < 0.001). In conclusion, within the conditions of the present study, long-term suppression of gram-negative bacteriuria by norfloxacin reduced the incidence of catheter-related urinary tract infection and associated morbidity.

An aqueous solution of norfloxacin nicotinate (NFN) was administered to donkeys (Aquus asinus) intravenously (once at 10 mg/kg), intramuscularly and orally (both routes once at 10 and 20 mg/kg, and for 5 days at 20 mg/kg/day). Blood samples were collected at predetermined times after each treatment and urine was sampled after intravenous drug administration. Serum NFN concentrations were determined by microbiological assay. Intravenous injection of NFN over 45-60 s resulted in seizures, profuse sweating and tachycardia. The intravenous half-life (t1/2 beta) was 209 +/- 36 min, the apparent volume of distribution (Vd(area)) was 3.34 +/- 0.58 L/kg, the total body clearance (ClB) was 1.092 +/- 0.123 x 10(-2) mL/min/kg and the renal clearance (C1R) was 0.411 +/- 0.057 x 10(-2) mL/min/kg. Oral bioavailability was rather poor (9.6% and 6.4% for the 10 and 20 mg/kg doses respectively). Multiple oral treatments did not result in any clinical gastrointestinal disturbances. After intramuscular administration (20 mg/kg), serum NFN concentrations > 0.25 microgram/mL (necessary to inhibit the majority of gram-negative bacteria isolated from horses) were maintained for 12 h. The intramuscular bioavailability was 31.5% and 18.8% for the 10 and 20 mg/kg doses respectively. After multiple dosing some local swelling was observed at the injection site. About 40% of the intravenous dose was recovered in the urine as parent drug. The results of comprehensive haematological and blood biochemistry tests indicated no abnormal findings except elevation in serum CPK (creatine phosphokinase) values after multiple intramuscular dosing.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of norfloxacin (NOR), at steady-state plasma concentrations of 0-32 mg.l-1, on the plasma clearance of a 6 mg.kg-1 i.v. bolus dose of theophylline (THEO) in the male Sprague-Dawley rat have been studied. The effects were characterised by a Ki value (Ki = 12 microM), which was comparable with Ki values obtained previously under identical conditions for ciprofloxacin, but higher than that obtained for enoxacin. The distributional characteristics, volume of distribution and liver to plasma concentration ratio, were very similar for the three compounds. The only marked pharmacokinetic differences were in hepatic clearance, where there was a rank order NOR > ciprofloxacin > enoxacin, a reverse of the order in the reduction of THEO clearance seen in clinical studies. The advantages of using the steady-state experimental design described here are that equivalent concentrations are utilised to compare related drugs and differences in pharmacokinetics are accounted for, to allow a direct comparison of potency. This information, together with additional pharmacokinetic considerations, suggests that the different effects on THEO clearance seen in the clinic for NOR, ciprofloxacin and enoxacin are not solely due to differences in inhibitory potency, but also involve differences in hepatic clearance and hence systemic availability of the fluoroquinolones.

Purpose: Bacterial contamination of anterior chamber at the end of cataract surgery, was compared between two techniques: extracapsular extraction and phacoemulsification. The effectiveness of preoperative antibiotic eyedrops using Norfloxacine 0.3% (Chibroxine) was also evaluated., Method: The study focused on 101 patients grouped according to surgical technique and presence of preoperative antibiotic eyedrops. Conjunctival sampling was made the day prior the surgery, as well as in the operating room, after skin and conjunctival desinfection with povidone iodine in all the patients included in the study. Aqueous humour was collected at the end of surgery., Results: Eight samples out of 101 were positive which represents 7.9% of the cases. In 75% of the cases, the anterior chamber aspirate showed a different germ or non-recurrent germ in the second conjunctival sample. None of the included patients developed endophthalmitis. The two most frequent pathogens were Propionibacterium acnes in 62.5% of the cases, and Staphylococcus epidermidis in 50%. Another pathogen was found in a culture environment: Micrococcus roseus. In two samples, two different bacteria grew: Propionibacterium acnes and Staphylococcus epidermidis. Whatever the surgical technique, no statistically significant bacterial contamination was found. There was no significant statistical difference between patients who had local antibiotic eyedrops and those who did not., Conclusion: This study confirms the poor reliability of local antibiotic eyedrops to prevent surgical contamination. Furthermore performing an anterior chamber aspirate at the end of the surgery for risk patients would help the physician identify the pathogens involved in endophthalmitis in order to begin antibiotic treatment as soon as possible.

The efficacy and tolerability of brodimoprim OD versus norfloxacin BID were studied in patients affected by bacterial urinary tract infections. The study was performed in 203 patients divided into two parallel randomized groups orally given either brodimoprim 400 mg OD on the first day followed by 200 mg OD for 2 days, or norfloxacin 400 mg BID respectively. The efficacy of treatment was evaluated by the bacterial cultures, tolerability, analysis of signs and symptoms, a complete physical examination and from laboratory data. The results showed that brodimoprim and norfloxacin in the majority of patients resulted in a reduction of fever and symptoms caused by the infective process. Of the 103 patients enrolled in the brodimoprim OD group, 99 had a complete course of therapy with a positive outcome. There was only one case of failed treatment and 3 cases which could not be evaluated because of voluntary interruption of treatment. Of the 100 patients treated with norfloxacin BID, 94 completed therapy with a positive clinical outcome and there were 4 cases of treatment failure. Thus the efficacy of brodimoprim OD appears comparable to that of norfloxacin BID in the treatment of urinary tract infections.

Biliary stents are liable to clog. We investigated whether a choleretic plus an antibiotic could delay clogging. 20 consecutive patients with a malignant biliary stricture were randomised after endoscopic insertion of a polyethylene stent to receive ursodeoxycholic acid plus norfloxacin (13-15 mg/kg and 400 mg, daily) or conservative treatment. The drug combination was associated with: a longer median patency of first (49 vs 6 weeks) and all stents (38 vs 7 weeks); a prolonged median survival (67 vs 18 weeks); and a shorter mean hospital stay (0.2 vs 1.0 days per week of survival). Thus ursodeoxycholic acid plus norfloxacin may prevent stent clogging.