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Aim:To investigate the pharmacokinetic interactions between zalcitabine andnonsteroidal anti-inflammatory drugs (NSAIDs) in rats.Methods:Zalcitabinewas administered to rats via an iv injection (20 mg/kg) in the presence or absenceof ketoprofen or naproxen (20 mg/kg),and the pharmacokinetic parameters weredetermined by using non-compartmental analysis.Results:Compared with thecontrol (zalcitabine alone),pretreatment with ketoprofen or naproxen 30 min priorto intravenous administration of zalcitabine significantly altered the pharmacoki-netic profiles of zalcitabine in rats.Renal clearance of zalcitabine was reduced byapproximately 3-4-fold in the presence of ketoprofen or naproxen.Consequently,systemic exposure (AUC) to zalcitabine in the rats pretreated with ketoprofen ornaproxen was significantly greater than that for the control group given zalcitabinealone.The terminal plasma half-life of zalcitabine was also prolonged by 4-5-foldin the presence of ketoprofen or naproxen.Conclusion:The NSAIDs ketoprofenand naproxen effectively altered the pharmacokinetics of zalcitabine.Therefore,concomitant use of ketoprofen or naproxen in patients being treated with zalcitabinemay necessitate close monitoring for potential drug interactions.
Aim: To investigate the pharmacokinetic interactions between zalcitabine and nonsteroidal anti-inflammatory drugs (NSAIDs) in rats. Methods: Zalcitabine was administered to rats via an iv injection (20 mg / kg) in the presence or absence of ketoprofen or naproxen (20 mg / kg) , and the pharmacokinetic parameters were determined by using non-compartmental analysis. Results: Compared with the control (zalcitabine alone), pretreatment with ketoprofen or naproxen 30 min priorto intravenous administration of zalcitabine significantly altered the pharmacoki-netic profiles of zalcitabine in rats. Renal clearance of zalcitabine was reduced byapproximately 3-4-fold in the presence of ketoprofen or naproxen. Conclusion, systemic exposure (AUC) to zalcitabine in the rats pretreated with ketoprofen ornaproxen was significantly greater than that for the control group given zalcitabinealone. the terminal plasma half- life of zalcitabine was also prolonged by 4-5-fold in the presence of ketoprofen or naproxen. Confclusion: The NSAIDs ketoprofen and naproxen effectively altered the pharmacokinetics of zalcitabine.Therefore, concomitant use of ketoprofen or naproxen in patients being treated with zalcitabinemay necessitate close monitoring for potential drug interactions.