Pharmacokinetic evaluation of anti-HIV drug interactions: effect of zidovudine on 2'-3'-dideoxyinosine kinetics in monkeys

The current investigation was conducted to determine if zidovudine (AZT) altered the pharmacokinetics of dideoxyinosine (ddl) in non-human primates, an appropriate animal model for AZT and ddl pharmacokinetics in human. Each of nine animals received 20 mg kg −1 of ddl intravenously in the absence and presence of two different dosage regimens of AZT. For each combination regimen, AZT was administered as a combined i.v. bolus-constant rate infusion regimen for 30 min that produced AZT plasma concentrations of about 4 μg ml −1 in six animals (low dose group) and 11 μg ml −1 in three others (high dose group). Serial blood samples were collected, and pharmacokinetic parameters for ddl were calculated based on plasma ddl concentrations measured by HPLC techniques