Altered pharmacokinetics of zalcitabine by concurrent use of NSAIDs in rats

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 prior
to intravenous administration of zalcitabine significantly altered the pharmacokinetic
profiles of zalcitabine in rats. Renal clearance of zalcitabine was reduced by
approximately 3–4-fold in the presence of ketoprofen or naproxen. Consequently,
systemic exposure (AUC) to zalcitabine in the rats pretreated with ketoprofen or
naproxen was significantly greater than that for the control group given zalcitabine
alone. The terminal plasma half-life of zalcitabine was also prolonged by 4–5-fold
in the presence of ketoprofen or naproxen. Conclusion: The NSAIDs ketoprofen
and naproxen effectively altered the pharmacokinetics of zalcitabine. Therefore,
concomitant use of ketoprofen or naproxen in patients being treated with zalcitabine
may necessitate close monitoring for potential drug interactions.