No interaction between ciprofloxacin and an oral contraceptive.

Several antibiotics have been reported to lessen the ovarian suppression produced by oral contraceptive agents, as a result of drug interactions. The present investigation was designed to study the likelihood of the occurrence of any such interaction between the fluoroquinolone antibiotic ciprofloxacin (Ciproxin) at a dosage of 500 mg twice a day and the "low-dose" oral contraceptive Marvelon (30 microgram of ethinyl estradiol [EE] plus 150 microgram of desogestrel). Twenty-four healthy female volunteers were studied in a double-blind, placebo-controlled, randomized crossover trial. There were no significant differences between measurements of the area under the concentration-time curve of EE up to 24 h after oral contraceptive intake during placebo and ciprofloxacin administration on days 11 and 16 of the cycles, indicating the absence of pharmacokinetic interaction. Similarly, no clinically significant differences in the levels of sex hormone binding globulin were found between the placebo and ciprofloxacin cycles, indicating no major variation in EE levels during ciprofloxacin and placebo treatment. Ten subjects in each of the placebo and ciprofloxacin groups had early-follicular-phase levels of 17-beta estradiol (<184 ng/liter) at one or more points during their cycles, but none had values above the early-follicular-phase range, indicating no significant ovarian activity. In addition, all subjects had progesterone levels of <2 ng/ml, indicating the absence of ovulation. Only two subjects, who received the placebo, had evidence of sustained follicular growth to a potentially ovulatory follicle ( approximately 18 mm). We conclude that ciprofloxacin does not interfere with the ovarian suppression produced by the low-dose oral contraceptive Marvelon.

PIP: A single-center, double-blind, placebo-controlled randomized crossover trial involving 24 healthy female volunteers, aged 19-32 years, was undertaken to assess whether ciprofloxacin (Ciproxin) affects the contraceptive effect of Marvelon (30 mcg of ethinyl estradiol [EE] plus 150 mcg of desogestrel). The study also evaluated the follicle ripening in ovaries by measuring the increase in mean follicular diameter in the subovulatory cycles during treatment with ciprofloxacin. The volunteers were divided into 2 blocks of 12 individuals, randomly allocated to 1 of 2 treatment order groups, with 6 individuals per group. One group received Marvelon, 1 tablet daily on days 8-28 of each cycle, and Ciprofloxacin or the placebo group administered twice daily on days 8-17 of cycles. Findings revealed that there were no significant differences between measurements of the area under the concentration-time curve of EE up to 24 hours after oral contraceptive intake during placebo and ciprofloxacin administration on days 11 and 16 of the cycles, indicating the absence of pharmacokinetic interaction. Similarly, no clinically significant differences in the levels of sex hormone binding globulin were found between the placebo and ciprofloxacin cycles, indicating no major variation in EE levels during ciprofloxacin and placebo treatment. In conclusion, ciprofloxacin does not appear to alter ovarian activity when co-administered with the low-dose oral contraceptive Marvelon. No evidence of pharmacokinetic interaction between the antibiotic and the contraceptive was detected.

No pharmacokinetic or pharmacodynamic interaction between theophylline and the leukotriene biosynthesis inhibitor BAY x 1005.

An open, randomized, three-period crossover study was conducted to compare the steady-state pharmacokinetics, pharmacodynamics, and tolerability of concomitant administration of BAY x 1005 and theophylline in 12 healthy volunteers. BAY x 1005 (250 mg twice daily; treatment A) and theophylline (400 mg twice daily; treatment B), were administered alone and concomitantly (treatment C) for 6 days with a final morning dose on day 7. The treatments were separated by washout periods of at least 5 days. Pharmacokinetic parameters were derived from concentrations of BAY x 1005 and theophylline as measured by high-performance liquid chromatography in plasma collected before the morning dose on days 5 and 6 and at various times on day 7 of each period until 24 hours after drug administration. Adverse events, vital signs, electrocardiograms, and clinical laboratory studies were monitored as safety parameters. Levels of leukotriene B4 (LTB4) were assessed in plasma collected on days 1 and 7. The treatments were well tolerated by all participants. The ratios of maximum concentration (Cmax) and area under the concentration-time curve for one 12-hour dosing interval (AUC tau) for treatment C versus B for theophylline on day 7 was 98% for both parameters. For BAY x 1005, the ratios of treatment C versus treatment A were 94% for Cmax and 101% for AUC tau. Plasma LTB4 remained virtually unchanged during either treatment. Steady-state concentrations of theophylline were not affected by concomitant BAY x 1005 intake, and addition of theophylline had no clinically relevant effect on steady-state plasma concentrations of BAY x 1005. The combination of theophylline and BAY x 1005 did not lead to a change in nature, intensity, or frequency of adverse events.

Pharmacokinetics of ciprofloxacin after intraperitoneal administration in uninfected patients undergoing CCPD.

Ciprofloxacin is increasingly used to treat peritoneal dialysis related peritonitis. We studied the pharmacokinetics of intraperitoneally administered ciprofloxacin in six uninfected CCPD patients. In a randomized cross-over setting ciprofloxacin was added either to a long dwell exchange (lastbag) or to four short dwell exchanges (dwell time 1.5 h). Addition of ciprofloxacin (25 mg/l) during the four short dwell exchanges resulted in dialysate levels of 21.1-13.3 mg/l during these exchanges. In the subsequent last bag devoid of ciprofloxacin a dialysate Cmax,D of 1.38 mg/l was observed at 30 min. Mean +/- SD serum Cmax,S was 0.59 +/- 0.29 mg/l after 5.4 h. Instillation of 100 mg/l ciprofloxacin in the last-bag yielded Cmax,D of 99.1 mg/l, falling with a t1/2 of 3.3 h towards levels < 2 mg/l at 19.8 h. A mean +/- SD serum Cmax,S of 0.69 +/- 0.19 was reached after 4 h. During four subsequent 1.5h exchanges without ciprofloxacin dialysate levels were < 0.1 mg/l. Instillation of 25 mg/l ciprofloxacin in the last-bag yielded a Cmax,D of 21.7 mg/l, falling towards levels < 2 mg/l at 15 h with a t1/2 of 3.85 h. A mean +/- SD serum Cmax,S of 0.26 +/- 0.03 was reached after 8 h. We conclude that the rapid absorption of ciprofloxacin from the dialysate into the tissues requires ciprofloxacin to be administered to all CCPD bags to ensure bactericidal dialysate levels. When therapeutic serum levels are required higher intraperitoneal doses or an oral or i.v. loading dose is warranted.