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Objective: Infection is a potential complication of transrectal needle biopsy of the prostate (TRNBP), and antibiotic prophylaxis with a fluoroquinolone is commonly used. The objective of this study was to demonstrate penetration of ciprofloxacin into prostate tissue after administration of a ciprofloxacin 1000 mg extended-release formulation prior to TRNBP., Subjects and Methods: The study enrolled 13 men aged 45-78 years scheduled for TRNBP. They received a single, 1000 mg, extended-release tablet of ciprofloxacin at about 3 hours or at about 1 hour prior to the scheduled biopsy time. Blood and urine samples were taken just prior to the biopsy procedure, and prostate tissue samples after all needle biopsy specimens required for diagnostic purposes had been obtained, for determination of ciprofloxacin concentrations. Population data from a previous crossover study of 25 healthy male volunteers was used to model the prostate tissue concentrations for extended-release ciprofloxacin up to 24 hours after administration. These data were used to predict the normal range data for the current study., Results: The mean sampling time in the 1-hour group was 1.47 hours (range, 1.25-1.75 hours) and in the 3-hour group was 3.27 hours (range, 3.03-3.42 hours) after ciprofloxacin dosing. The mean concentrations of ciprofloxacin at 1 hour and 3 hours were 4.75 +/- 1.33 microg/g and 4.29 +/- 1.61 microg/g in prostate tissue, 2.11 +/- 1.00 mg/L and 3.08 +/- 1.44 mg/L in serum, and 126.2 +/- 141.7 mg/L and 803.3 +/- 596.3 mg/L in urine. The mean prostate : serum ciprofloxacin concentration ratio was 1.9 : 1 for the 1-hour group and 1.6 : 1 for the 3-hour group. The measured concentrations of ciprofloxacin in prostate tissue fell within the range modelled from the pharmacokinetic data from the 25 healthy, male subjects. No drug-related adverse events were reported., Conclusions: Extended-release ciprofloxacin is well tolerated and penetrates effectively into prostate tissue. Tissue levels of ciprofloxacin are similar whether the extended-release ciprofloxacin is administered 1 hour or 3 hours before TRNBP, indicating that tissue levels are maintained for several hours after administration. PK modelling as used in this trial is suitable to prospectively outline clinical designs. Further investigation of single-dose, extended-release ciprofloxacin as prophylaxis for TRNBP is warranted.

Objective: Information about the pharmacokinetics of fluoroquinolone antibiotics in high risk children is scant. This study examined the disposition of sequentially administered intravenous and oral ciprofloxacin, as well as provided dosing recommendations, for the treatment of acute pulmonary exacerbations in pediatric cystic fibrosis patients., Methods: After enrollment in a Food and Drug Administration approved protocol, the pharmacokinetic profiles of ciprofloxacin (CIP) administered to 18 children with cystic fibrosis (ages 5 to 17 years) were studied at steady state after sequentially administered intravenous (10 mg/kg every 8 h) and oral (20 mg/kg every 12 h) doses. All children enrolled met published criteria for exacerbation of Pseudomonas aeruginosa lung infection and received CIP intravenously (given as a 1-h infusion) followed by oral administration, each for a minimum of 3 days. All patients were at a mild to moderate stage in their disease with National Institutes of Health scores between 37 and 83. Blood samples were drawn at 0, 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0 (after both i.v. and oral dosing) and 12 h (oral only) after CIP administration. CIP serum concentrations were determined by high performance liquid chromatography., Results: After oral CIP mean +/- SD peak serum concentrations and peak times were 3.7 +/- 1.4 mg/l and 2.5 +/- 1.8 h, respectively, compared with 5.0 +/- 1.5 mg/l and 1.0 +/- 0.3 h after completion of the i.v. infusion. Maximum concentrations, when normalized for dose, were 0.52 +/- 0.12 and 0.19 +/- 0.07 mg/l/kg after i.v. and oral dosing, respectively. The mean bioavailability of oral CIP for all patients was 76%; younger patients appeared to absorb oral CIP less than older subjects, 68% vs. 95%, respectively. For all patients elimination half-lives were 2.6 +/- 0.6 and 3.4 +/- 0.7 h after i.v. and oral administration, respectively, and did not differ by age. Total clearance after i.v. administration was 19.5 +/- 10.9 liters/h. No significant CIP-related adverse effects were noted., Conclusions: CIP doses of 30 mg/kg/day i.v. and 40 mg/kg/day orally must be administered to children with cystic fibrosis to achieve optimal therapeutic concentrations.

The pharmacokinetics of intravenous ciprofloxacin and its metabolites were characterized in 42 subjects with various degrees of renal function (group 1, Clcr (mL/min/1.73 m2) > 90, n = 10; group 2, Clcr 61-90, n = 11; group 3, Clcr 31-60, n = 11; group 4, Clcr < or = 30, n = 10). The dosage regimens were-groups 1 and 2: 400 mg i.v. at 8 hourly intervals; group 3: 400 mg i.v. at 12 hourly intervals and group 4: 300 mg i.v. at 12 hourly intervals. Subjects received a single dose on days 1 and 5 and multiple doses on days 2-4. Multiple plasma and urine samples were collected on days 1 and 5 for the analysis of ciprofloxacin and its metabolites (M1, M2 and M3). Plasma concentrations (Cmax and AUC) of ciprofloxacin and its M1 and M2 metabolites were significantly increased in subjects with reduced Clcr values (Clcr < 60 mL/min/1.73 m2) compared with normal subjects (Clcr > 90 mL/min/1.73 m2). A positive correlation was observed between ciprofloxacin clearance (Cl) and Clcr with a slope of 0.29 (r2 = 0.78) and between renal clearance (Clr) and Clcr with a slope of 0.19 (r2 = 0.84). For patients with severe infections a dosage regimen of 400 mg iv 8 hourly is appropriate in patients with Clcr > 60 mL/min/1.73 m2. In patients with Clcr values of 31-60 mL/min/1.73 m2 a dosage regimen of 400 mg 12 hourly provides similar plasma concentrations to those observed for subjects with Clcr 61-90 mL/min/1.73 m2 receiving 400 mg 8 hourly. Based on modeling of the plasma concentrations in subjects with Clcr < or = 30 ml/min/1.73 m2, a dosage regimen of 400 mg every 24 h will provide plasma concentrations similar to those observed in subjects with Clcr between 61-90 mL/min/1.73 m2 given 400 mg every 8 h.

Many drugs exhibit altered pharmacokinetic parameters in burn patients. We prospectively evaluated the pharmacokinetics of ciprofloxacin in eight burn patients with active infections. Each patient received a 400-mg dose of ciprofloxacin intravenously (i.v.) every 8 h, with each dose infused over 1 h by using a rate control device. Blood samples for analysis of plasma ciprofloxacin concentrations, determined by high-performance liquid chromatography, were obtained immediately predose, at the end of the infusion, and 1, 2, 3, 4, 5, 6, and 7 h after the end of the infusion. Urine was collected from 0 to 2, 2 to 4, and 4 to 8 h following the same dose, and an aliquot was saved for determination of the ciprofloxacin concentration. Urine was also collected for 24 h prior to this dose for measurement of creatinine clearance (CLCR). Pharmacokinetic parameters were estimated by noncompartmental analysis. Mean maximum and minimum plasma ciprofloxacin concentrations were 4.2 +/- 1.1 and 0.70 +/- 0.55 microgram/ml, respectively. Mean values for clearance (CL), renal clearance (CLR), volume of distribution, terminal elimination rate constant, half-life (t1/2), and area under the concentration-time curve (AUC) were 29.1 +/- 17.5 liters/h, 13.5 +/- 10.1 liters/h, 1.75 +/- 0.41 liters/kg, 0.222 +/- 0.098 h-1, 4.5 +/- 3.9 h, and 20.7 +/- 16.6 micrograms.h/ml, respectively. CL was higher and t1/2 was shorter than noted in previous studies of acutely ill, hospitalized patients. A good correlation was noted between creatinine clearance CL(CR) and both total ciprofloxacin CL (r = 0.85) and CLR (r = 0.84). A moderate inverse correlation was noted between percent body surface area burned and total ciprofloxacin CL (r = -0.55). An AUC/MIC ratio above 125 SIT-1 (where SIT is serum inhibitory titer), which has been strongly correlated with clinical response and time to bacterial eradication, was achieved in five of eight patients (63%) with a MIC of 0.25 microgram/ml. At a ciprofloxacin dosage of 400 mg i.v. every 12 h, an AUC/MIC ratio above 125 SIT-1 would have been achieved in only two of eight patients (25%). We conclude that ciprofloxacin CL is highly variable, but generally increased, in burn patients compared with that in acutely ill, general medical and surgical patients. Because of an increase in CL, a ciprofloxacin dosage of 400 mg i.v. every 8 h is more likely to produce the desired response in burn patients than the same dose given every 12 h.

To determine if ciprofloxacin therapy alters the response to warfarin treatment, 36 adult patients attending three university-affiliated outpatient anticoagulation clinics randomly received a 12-day course of ciprofloxacin (750 mg twice daily) and a 12-day course of placebo; each course was separated by a 2-week washout period. Prothrombin times (PTs), concentrations of S-warfarin and R-warfarin (the isomers of warfarin), and concentrations of clotting factors II and VII were determined three times weekly for 9 weeks. By day 12 of ciprofloxacin therapy, concentrations of S-warfarin remained unchanged compared with those after placebo therapy, but R-warfarin concentrations increased significantly (1.15 times those after placebo therapy; P = .001); concentrations of clotting factors II and VII decreased (0.903 and 0.872 times those after placebo therapy, respectively, P < or = .020). The mean PT ratio after 12 days of ciprofloxacin therapy increased slightly (1.032 times that after placebo therapy; P = .057), but no patient had bleeding or a change in PT that required alteration in warfarin or ciprofloxacin therapy. We conclude that warfarin therapy is not a contraindication to the use of ciprofloxacin.

The effects of age and gender on the pharmacokinetics of high-dose intravenous ciprofloxacin in a healthy volunteer study were investigated. Plasma ciprofloxacin concentrations were higher in the elderly than in the young, and the pharmacokinetic parameters were not significantly different between the genders. Ciprofloxacin was well tolerated, with the majority of adverse events related to local reactions at the IV site.

Comparative pharmacokinetics of i.v. and oral ciprofloxacin was studied in 24 healthy male subjects given 400 mg i.v. tds or 750 mg po bd in a randomized, double-blind, placebo controlled, crossover fashion with at least a 10 day washout period. Blood and urine samples were obtained following the first (single dose) and last (steady state) dose in each treatment period. After single dosing and under steady state conditions, the calculated 24 h area under the serum concentration versus time curve, (AUC0-24) after 400 mg i.v. tds (AUC0-8 x 3) was equivalent to the AUC0-24 after 750 mg po bd (AUC0-12 x 2). Peak serum concentrations produced by the i.v. regimen were very similar to those observed after the 750 mg oral dose. The extent of accumulation was similar following either dosing regimen and was approximately 35%. Overall, the incidence of adverse effects (none of which was serious) was higher with the i.v. regimen than with the oral regimen, mainly due to injection site reaction, which was the most commonly reported adverse event.

The pharmacokinetic parameters of intravenous ciprofloxacin were examined in five adult male patients on three separate occasions of open heart surgery: the 24 h before cardiopulmonary bypass (CPB) surgery, (PRE), during surgery (SURG), and 48 to 72 h after surgery (POST). Serial blood (n = 16), urine, and SURG tissue samples were collected after intravenous administration of a single 300-mg dose of ciprofloxacin during each study period. All samples were assayed for ciprofloxacin by a specific high-performance liquid chromatographic method. Serum ciprofloxacin concentrations remained constant or continued to decline during the course of CPB surgery. A significant (P < 0.05) decrease in total body clearance was observed during the SURG and POST phases (298 and 306 ml/min/1.73 m2, respectively) compared with that during the PRE phase (364 ml/min/1.73 m2). Renal clearances and elimination half-lives were similar during all three study phases. A nonsignificant decline occurred in the apparent volume of distribution, from mean values of 2.1 and 2.0 liters/kg during the PRE and POST phases, respectively, to 1.7 liters/kg during the SURG phase. The mediastinal fat tissue ciprofloxacin concentrations ranged from 0.45 to 2.89 micrograms/g. Overall, little significant difference was noted in the disposition of intravenous ciprofloxacin during CPB surgery compared with that before and after surgery.

Ciprofloxacin was administered to 12 healthy male volunteers at doses of 300 and 400 mg intravenously (i.v.) and 500 and 750 mg orally in a randomized, double-blind, single-dose, four-period crossover study. On each treatment day, each subject received both oral and i.v. formulations, one of which was a placebo. Blood and urine samples were obtained through 24 h postdose. By each dosing route, the pharmacokinetic profiles were dose proportional. The 400-mg i.v. dose was equivalent to the 500-mg oral dose with respect to the area under the concentration-time curve and was equivalent to the 750-mg oral dose with respect to the maximum concentration of ciprofloxacin in serum. The oral bioavailability was 78.0%. The steady-state volume of distribution averaged 178 liters, and the terminal half-life in serum after i.v. dosing was approximately 4.3 h. Renal clearance accounted for approximately 60% of total body clearance. No significant adverse events were associated with either route of administration.

This study was designed to determine the effects of an aluminum hydroxide antacid and a calcium carbonate antacid on the bioavailability of ciprofloxacin (Cipro). Cipro (750 mg) was administered orally to 12 healthy volunteers in a three-way randomized crossover design. The three treatments included Cipro alone, four 850-mg calcium carbonate tablets taken 5 min before Cipro, and three 600-mg aluminum hydroxide tablets taken 5 min before Cipro. The relative bioavailability of Cipro when given with calcium carbonate was approximately 60% of the control value. When Cipro was given with aluminum hydroxide, the relative bioavailability was approximately 15%. Urinary recovery of Cipro in the aluminum hydroxide treatment group was approximately one-fourth of that in the calcium carbonate group. Although calcium carbonate decreased absorption to a lesser extent than aluminum hydroxide, these data suggest that antacids containing either aluminum or calcium should not be given concomitantly with Cipro.

The effect of a multiple-dose regimen of oral ciprofloxacin (750 mg every 12 h for 11 doses) on the clearance and steady-state concentrations of theophylline in trough (predose) serum was evaluated in nine healthy male subjects, each serving as his own control. Theophylline was taken as a sustained release tablet per os in a dose of 200 mg every 12 h for 19 doses. Theophylline concentrations in serum were measured immediately before each theophylline dose. Ciprofloxacin was administered on study day 4 through the first dose of study day 8. Theophylline concentrations in serum were also measured on study days 3, 6, 8, and 10 at the following times after the first dose of each day: 0, 0.25, 0.50, 1, 2, 4, 6, 8, 10, and 12 h. Steady-state theophylline concentrations in trough serum were significantly higher during ciprofloxacin treatment (day 8) than before (day 3) or after (day 10) ciprofloxacin administration (P less than 0.01). Likewise, theophylline clearance was significantly slower (P less than 0.01) during ciprofloxacin treatment (day 8) than before it (day 3) or after it (day 10). The magnitude of ciprofloxacin-induced changes was approximately 30%. These results suggest that a multidose regimen of ciprofloxacin significantly slows the clearance of theophylline and elevates theophylline concentrations in serum.

The pharmacokinetics of ciprofloxacin, a carboxyquinolone, was studied after oral administration of the drug to seven patients with biopsy-proved cirrhosis and to seven healthy volunteers. Serum concentrations of ciprofloxacin and its three metabolites--desethylene ciprofloxacin (M1), sulfociprofloxacin (M2), and oxociprofloxacin (M3)--were measured by an HPLC procedure. The pharmacokinetic parameters for ciprofloxacin were not significantly altered in cirrhotic patients. The elimination half-life (t 1/2) and the area under the serum concentration versus time curve (AUC) were, respectively, 3.71 hours and 16.18 microgram.ml-1.hr-1 in the normal subjects and 3.47 hours and 18.38 micrograms.ml-1.hr-1 in patients with cirrhosis. The formation of oxociprofloxacin was reduced by approximately one half in the cirrhotic subjects, as the Cmax was 0.29 micrograms/ml in normal subjects versus 0.14 micrograms/ml in cirrhotic patients and the mean AUC(0-t) was 1.54 micrograms.ml-1.hr-1 in normal subjects versus 0.70 micrograms.ml-1.hr-1 in cirrhotic patients. However, there appeared to be no significant difference between groups with respect to desethylene ciprofloxacin and sulfociprofloxacin. Therefore it appears from this study that no dosage adjustment is required in patients with hepatic cirrhosis.

The bioavailability of ciprofloxacin after its administration through a nasogastric (NG) feeding tube was studied in six healthy volunteers. Each subject received, on separate occasions, an intact 750-mg ciprofloxacin tablet, a crushed tablet as a suspension through an NG tube, and a crushed tablet as a suspension through an NG tube while receiving enteral feeding. No statistically significant differences were observed in the area under the curve, maximum concentration in serum, and time to peak concentration among these three modes of administration. These findings suggest that ciprofloxacin is well absorbed after administration via an NG tube (compared with an orally administered intact tablet) even in the presence of enteral feeding.

The purpose of the research was to ascertain the comparative differences of quinolone antibiotics on theophylline pharmacokinetics. Eight healthy male volunteers were randomly assigned to four treatments. Each was administered norfloxacin (NOR) 800 mg/d, ciprofloxacin (C) 1 g/d, nalidixic acid (NAL) 2 g/d and placebo (P) for 7 days. On the seventh day of each treatment, theophylline (5 mg/kg) iv was administered. The elimination half-life (T 1/2), total body clearance (CL) and volume of distribution at steady state (Vss) of theophylline were calculated using model-independent methods. ANOVA for repeated measures was used for data comparisons. The mean (SD) theophylline results were: CL l/kg/h--NOR .038 (.006), C .033 (.006), NAL .045 (.008), P .044 (.007); T 1/2 h--NOR 9.2 (1.8), C 10.6 (1.8), NAL 8.3 (1.8), P 7.5 (1.4). Theophylline Vss differences by treatment were not significant. NOR and C significantly decreased theophylline's clearance and the clearance change can be of clinical significance.

The effect of an antacid (Maalox) and ranitidine administration on the absorption of ciprofloxacin was evaluated in healthy male volunteers who were enrolled in three separate studies. Each study was designed at a three- or four-period crossover and included the administration of 750 mg ciprofloxacin alone as a control treatment. Treatments that were evaluated included the administration of ciprofloxacin 5 to 10 minutes, 2 hours, 4 hours, and 6 hours after a single 30 ml dose of antacid; the administration of antacid 2 hours after ciprofloxacin was given; and the administration of ciprofloxacin 2 hours after a 200 mg ranitidine tablet. Administration of antacid within 4 hours before ciprofloxacin dose resulted in a significant decrease in ciprofloxacin absorption (p less than 0.05). Percentages of relative bioavailability compared with control values were 15.1%, 23.2%, and 70% for the 5 to 10 minute, 2 hour, and 4 hour antacid pretreatments, respectively. Administration of antacid 6 hours before or 2 hours after the ciprofloxacin dose did not affect absorption. Ranitidine did not alter ciprofloxacin absorption. Antacids that contain magnesium and aluminum salts may reduce the absorption of ciprofloxacin. The extent of this interaction appears to increase as the time between administration of the two drugs decreases. Ranitidine is suggested as an alternative to antacids for patients receiving treatment with ciprofloxacin.