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Fluoroquinolones present various pharmacokinetic properties. That's the way we carried out a bibliographic summary about the pharmacokinetics of pefloxacin, ofloxacin and ciprofloxacin in patients hit by chronic renal failure, under haemodialysis or under continuous ambulatory peritoneal dialysis. Then, we will describe how to adapt drug dose according to the degree of renal insufficiency and the used molécule.

Ageing generates an important inter- and intra-individual variability in drug pharmacokinetics. The increasing frequency of ofloxacin adverse effects in elderly patients results from increased ofloxacin plasma levels about two or threefold over normal concentrations. A retrospective study of ofloxacin population pharmacokinetics in 17 elderly patients (83.6 +/- 6.8 years) shows the existence of three subgroups according to ofloxacin total clearance [group 1: 1.44 l/h, group 2: 4.37 l/h and group 3: 15.08 l/h] reflecting the important inter-individual variability. No correlation between this clearance and creatinine clearance, nor between this clearance and age, could be established, showing the limits of traditional drug monitoring in the elderly. Ofloxacin pharmacokinetic parameters estimated by the non-parametric software NPEM2 in the 17 elderly patients (absorption rate constant, Ka: 2.668 +/- 1.256 h-1; apparent volume of distribution related to weight, Vs: 1.272 +/- 0.778 l/kg; elimination rate constant, Ks: 0.265 +/- 0.247 10(-3) min/ml/h) are clearly different from those estimated in young adults. These results show the limits of classic drug monitoring in the elderly, and also the interest of adaptive control of a drug regimen.

Antibacterial activity of ofloxacin in urine after a single oral dose of 400 mg was evaluated in ten healthy female volunteers. Urine was collected over six periods, i.e., 0-6 h, 6-12 h, 12-24 h, 24-48 h, 48-72 h, and 72-96 h postdose. Ofloxacin levels were assayed in all samples using a microbiological method and HPLC. Urinary ofloxacin MICs were determined for five bacterial strains recovered from urine, two E. coli strains of which one was susceptible and the other resistant to nalidixic acid (Nal-A), one Klebsiella pneumoniae resistant to nalidixic acid (Nal-B), one Staphylococcus saprophyticus strain, and one Enterococcus faecalis strain; MICs were 0.06, 0.25, 1, 0.25, and 2 mg/L, respectively. Mean urinary ofloxacin levels by the microbiological method during the six collection periods were 193.3 +/- 30.3, 138.1 +/- 31, 53.2 +/- 7.3, 8.3 +/- 0.8, 1.4 +/- 0.2, and 0.6 +/- 0.1 mg/L, respectively. HPLC provided similar results: 216.7 +/- 31.6, 130.7 +/- 20.5, 56.5 +/- 7.1, 8.3 +/- 0.9, 1.5 +/- 0.3, and 0.5 +/- 0.05 mg/L, respectively. Mean urinary ofloxacin excretion over 96 h was 67.4 +/- 3.6% of the dose by the microbiological method was 72.5 +/- 2.5% of the dose by HPLC. On the first day, bacteriostatic activity of urine against enterobacteria exceeded 32 and was greater than 8192 for the nalidixic acid-susceptible E. coli strain; on the next day, overall values were equal or greater than 8 for the nalidixic acid-resistant E. coli and K. pneumoniae strains. Bacteriostatic activity was equal to or greater than 32 for the S. saprophyticus strain during the first two days and equal to 8 on the first day and 4 on the second day for the E. faecalis strain.

The influence of a non steroidal antiinflammatory drug (NSAID), ketoprofen, on the pharmacokinetics of two fluoroquinolone derivatives, pefloxacin (P) and ofloxacin (O), was studied in ten healthy adult male volunteers. The subjects were given orally for three days the quinolone alone (P: 400 mg q 12 h and O: 200 mg q 12 h), with at least a one week interval between the two quinolone studies. On day 4, the first kinetic study of pefloxacin and ofloxacin was performed. During the three following days, the quinolone was administered in association with ketoprofen (100 mg daily). Another pharmacokinetic study of P and O was performed on day 8 and the kinetic data obtained were compared to those found on day 4. During the two kinetic studies (D4 and D8), blood samples were taken at times 0, 1, 2, 3, 4, 6, 8, 10, 12 et 24 h and urine was collected during the time-periods 0-4 h, 4-8 h, 8-12 h and 12 24 h. Plasma and urine concentrations of the active P and O drug were measured by microbiological assay. Ketoprofen administered for three days with the fluoroquinolone derivative induced no statistical modification in the kinetic parameters of both P and O: peak plasma levels, time to peak level, areas under the curve, apparent volume of distribution, total and renal clearances.

The diffusion of ofloxacin in infected and healthy human and rabbit eyes was investigated. In the human study, cataract surgery patients were given intravenous ofloxacin either as a single 200 or 400 mg dose or as two 400 mg infusions 12 hours apart. Samples of aqueous humor and plasma were collected between 1 and 12 hours after the end of the infusion. Levels in the anterior chamber increased with the dose; peak levels, which occurred after three hours, were 0.33 mg/l after 200 mg and 1.24 mg/l after two 200 mg doses given 12 hours apart. In the rabbit study, 16 hours after experimental infection of the left eye by injection of S. epidermidis into the vitreous, animals were given an intraperitoneal injection of 20 or 50 mg/kg ofloxacin. Dosages in the various ocular tissues showed that penetration into the eye varied with race (albinos greater than pigmented) and dose. Intraocular ofloxacin levels, including in the vitreous, increased two fold when the eye was infected; however, penetration into the sclera, choroid, and retina was comparable in infected and noninfected eyes. These findings in humans and animals suggest that ofloxacin in a dose of a least 400 mg is a useful agent for the treatment of prophylaxis of ocular infections.

The kinetics of the effect of fusidic acid and of two fluoropiperazinyl quinolones (ofloxacin and pefloxacin), used alone or in combination, on ten methicillin-susceptible or methicillin-resistant strains of staphylococci were studied. Little or no bactericidal effects were seen with fusidic acid. With ofloxacin and pefloxacin, the bactericidal effect was delayed and occurred only with high concentrations. Used in combination, fusidic acid and the fluoroquinolones exhibited no synergistic effects and occasionally antagonized each other in vitro. The methicillin-resistance phenotype of organisms had no influence on results.

The pharmacokinetics of ofloxacin orally administered were investigated at the steady-state in sixteen elderly patients older than 65 years. Patients with either urinary tract of respiratory tract mild infectious were divided into two age-dependent groups A and B. Group A: eight patients (65-80 years) received 200 mg of ofloxacin by the oral route every 12 hours and group B: eight patients older than 80 years, received 200 mg of ofloxacin by the oral route every 24 hours. The pharmacokinetic study was performed on treatment day 5. Plasmatic levels and urinary excretion of ofloxacin during 12 or 24 hours were assayed by means of high pressure liquid chromatography. Wide variations in plasma ofloxacin concentrations were observed within each group (Cmax range, group A: 1.9-9.2 mg/l, group B: 1.6-10.0 mg/l). Similar variability was observed for ofloxacin elimination parameters (CI/F, renal CI(R)/F) and half-life. In contrast, within-group and between-group differences in the volume of distribution adjusted for weight were not significant (group A: 1.22 +/- 0.44 l.kg; group B: 1.49 +/- 0.53 l.kg), but these values were approximately half those observed in the young adult. Plasmatic [CI/F] and renal clearance [CI(R)/F] of ofloxacin were correlated with creatinine clearance in both groups and in the overall population studied. Then the overall population was classified in terms of creatinine clearance [group 1: greater than 50 ml/min; group 2: less than or equal to 50 (minimum 20) ml/min]. The pharmacokinetics of ofloxacin in the elderly are characterized by a decrease in the volume of distribution and in plasmatic and renal clearances.(ABSTRACT TRUNCATED AT 250 WORDS)

The uptake of ofloxacin by Escherichia coli NIHJ-JC2 was determined by a sensitive and convenient method using high-performance liquid chromatography (HPLC) with a fluorometric detection (sensitivity level: 1 ng/ml). Concentrations of ofloxacin were measured in bacteria after contact with 5 micrograms/ml of antibiotic for 1, 2, 3, 5, 10, 20 and 30 min. Ofloxacin uptake was rapid, 70% of broth concentration occurring within the first min and 96% after 5 min; then it reached a plateau which was 1.16 times as high as the broth concentration.

Ofloxacin belongs to the family of the fluoroquinolones whose structure has considerably improved the antibacterial activity of the pharmacokinetics properties of this type of antibiotics. The fluoroquinolones inhibit the DNA bacterial gyrase preventing the curling of the bacterial nucleic acid inside the nucleus. The spectrum of activity of ofloxacin contains most of the Gram-negative bacteria, the Gram-positive cocci with a lesser activity on the pneumococci and the methicillin-resistant staphylococci. Ofloxacin is not active on certain anaerobic mycobacteria. It is active on certain mycobacteria. The preferential indications of ofloxacin are low urinary or complicated infections, genital infections for example with gonococcus, osteoarticular infections and diarrhoea. For respiratory infections, ofloxacin can be recommended in the treatment of bronchial over-infections with negative Gram in chronic bronchial patients or in the course of the mucoviscidosis and infections of the ORL sphere (otitis, sinusitis) when repeated or when they become chronic. The high tolerance of ofloxacin makes it easier to use as it exists in both oral and injectable forms permitting easy use in hospitals.

The principal pharmacokinetic values of pefloxacin, ofloxacin and ciprofloxacin were obtained from a review of the literature. Following oral or intravenous administration of these three quinolones in the usual doses, pefloxacin was found to have the highest maximum serum concentration and the longest half-life. Ciprofloxacin had the highest antibacterial activity in vitro against Enterobacteriaceae, Haemophilus spp. and Pseudomonas spp., but all three drugs had the same activity against Staphylococcus aureus. These data enabled us to calculate the serum inhibitory quotients at peak level (usual dose maximum serum concentration minimum 50 percent inhibitory concentrations ratio). The highest inhibitory quotients were obtained with ciprofloxacin on Enterobacteriaceae and Pseudomonas spp. and with pefloxacin on Staph. aureus. Pefloxacin, ofloxacin and ciprofloxacin had the same inhibitory quotients on Haemophilus spp.

The pharmacokinetics of ofloxacin was studied in 12 intensive care patients, 6 of whom being under mechanical ventilation. All patients had a creatinine clearance greater than 60 ml/min/1.73 m2 and they were given 3 mg/kg. IV ofloxacin within 30 mn, with a twice daily regimen for 7 days. Pharmacokinetic studies were performed on day 1 (D1) and 7 (D7). Between D1 and D7 a significant increase in T 1/2 beta, AUC and blood levels were observed together with a decrease in total body clearance. Creatinine clearance was not modified between D1 and D7 but ofloxacin renal clearance was considerably altered. Abnormalities in ofloxacin renal tubular secretion may account for the drug cumulation which was observed during repeated administration in intensive care patients.

The ofloxacin diffusion was investigated in 13 cirrhotic patients with spontaneous bacterial peritonitis. Plasma and ascitic samples were collected at times H1, H31 and H8 after a first dose of 200 mg per os, in these 13 patients, after 4.5 or 6 days of 200 mg per os each 8 hours in 9 out of them. After the first dose, the plasmatic and ascitic concentrations, measured by High Performance Liquid Chromatography (HPLC), were between 0 and 3.62 mg/l, 0 and 1.95 mg/l respectively. The steady state concentrations are higher than the MIC'S for the organisms most commonly involved, comparable in the plasma and the ascitic fluid is good and suggest the interest of its use in this indication.