Pharmacokinetic evaluation of drug interactions with anti- human immunodeficiency virus drugs. VI. Effect of the calcium channel blocker nimodipine on zidovudine kinetics in monkeys

Coadministration of zidovudine (AZT) and nimodipine, a calcium-channel blocker, is a potential therapeutic regimen in acquired immunodeficiency syndrome patients based on the report that nimodipine can prevent human immunodeficiency virus-induced neurotoxicity in vitro. An evaluation of the pharmacokinetics of AZT and its glucuronide metabolite 3'-azido-3'-deoxy-5'-O-β-D- glucopyranurosylthymidine (GAZT) in the presence and absence of nimodipine in monkeys was undertaken. After 20 mg/kg of AZT given i.v. in the presence and absence of nimodipine, nimodipine caused a significant reduction (41%) in the volume of distribution of AZT at steady state and a 22% decrease in total clearance. The disposition of GAZT was also influenced by nimodipine, causing a large increase in its area under the plasma concentration-time curve. Renal excretion data for AZT and GAZT, although inconclusive, suggested nimodipine caused a decrease in the renal clearance of AZT with a minimal change in the renal clearance of GAZT. The combined effects of nimodipine on the clearance of AZT and volume of distribution at steady state produced no change in its elimination half-life.