Metabolic interactions of ciprofloxacin.
The mechanism and clinical relevance of the inhibitory effect of ciprofloxacin on the metabolism of selected drugs were studied in patients with bacterial infections. In study A, antipyrine tests were carried out in two groups of patients taking 1000 mg (group 1) and 250 mg (group 2) of oral ciprofloxacin for 7-10 days. Antipyrine was given intravenously in a dose of 15 mg/kg body weight before and after ciprofloxacin treatment. Blood samples were taken at 0, 2, 4, 6, and 10 hr after dosing. In group 1, ciprofloxacin administration resulted in a significant decrease in antipyrine elimination (t1/2, 9.45 +/- 3.74 vs. 14.92 +/- 3.32 hr). The average decrease in antipyrine clearance was 35% (0.85 +/- 0.45 vs. 0.52 +/- 0.24 ml/min/kg). In group 2, the change in antipyrine kinetics was less pronounced (t1/2, 9.79 +/- 3.06 vs. 11.22 +/- 2.64 hr). Antipyrine clearance was decreased by only 10% (0.77 +/- 0.13 vs. 0.70 +/- 0.14 ml/min/kg). These results support the hypothesis that ciprofloxacin inhibits the oxidative metabolism in the liver. However, according to the analysis of variance data, the inhibitory effect is dose dependent. At a dose of 1000 mg daily, ciprofloxacin may induce drug interactions whereas, at a dose of 250 mg daily, the likelihood of drug interactions is improbable. In study B, cimetidine (1000 mg orally daily) and ciprofloxacin (500 mg twice daily) were administered simultaneously to eight patients. Blood samples for the determination of ciprofloxacin concentrations were taken at 0, 1, 2, 4, 6, and 12 hr after dosing on the first and seventh day of drug administration.(ABSTRACT TRUNCATED AT 250 WORDS)
Ludwig
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Department of Medicine and Clinical Pharmacology, Péterfy Teaching Hospital, Budapest, Hungary.
Graber
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Székely
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Csiba
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A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D000983:Antipyrine / Q000378:metabolism*; D001424:Bacterial Infections / Q000188:drug therapy*; D002927:Cimetidine / Q000627:therapeutic use*; D002939:Ciprofloxacin / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D006801:Humans; D008795:Metronidazole / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008875:Middle Aged; D012044:Regression Analysis
D008795:Metronidazole; D002939:Ciprofloxacin; D002927:Cimetidine; D000983:Antipyrine