Effect of ciprofloxacin on antipyrine pharmacokinetics and metabolism in rats.

The effect of ciprofloxacin pretreatment on the pharmacokinetics and metabolism of antipyrine in male rats was studied. The animals received oral antipyrine (20 mg/kg of body weight) with and without ciprofloxacin pretreatment (40 mg/kg orally once a day for 8 days). The total plasma clearance of antipyrine was decreased from 0.130 +/- 0.007 to 0.090 +/- 0.005 liter/h (mean +/- standard error of the mean) (P less than 0.01) by ciprofloxacin, while the half-life at beta (elimination) phase and the area under the concentration-time curve for antipyrine were increased from 1.90 +/- 0.22 to 2.83 +/- 0.29 h (P less than 0.05) and from 43.25 +/- 3.35 to 52.41 +/- 2.31 mg.h/liter (P less than 0.05), respectively. The urinary excretions of norantipyrine, 4-hydroxyantipyrine, and 3-hydroxymethylantipyrine decreased by 73, 43, and 54%, respectively (P less than 0.001), in the 96 h after ciprofloxacin treatment. In addition, the rate constants for formation of each of these metabolites were significantly decreased, by an average of approximately 75%. These results suggest that ciprofloxacin is capable of inhibiting oxidative metabolism. This finding could be of clinical significance for drugs that are highly dependent of metabolic pathways, such as those inhibited in this study.