Zidovudine bioavailability and linear pharmacokinetics in female B6C3F1 mice

The bioavailability and pharmacokinetics of zidovudine (3'-azido-3'-deoxythymidine) (AZT) were determined in female B6C3F1 mice after administration of 15, 30, and 60 mg/kg doses via oral gavage or intravenous injection. Three animals in each administration group were sacrificed, and blood samples were collected at each of the following times: 0, 5, 10, 15, 20, 30, 45, 60, 75, 90, 105, and 120 min after drug administration. Plasma zidovudine concentrations were determined by HPLC. After oral administration, mean maximum plasma concentrations (Cmax) of 9.1, 18.9, and 40.3 mg/liter were observed at 18.3, 21.7, and 15.0 min (tmax) for the 15, 30, and 60 mg/kg doses, respectively. Following intravenous administration, mean Cmax values of 15.9, 41.8, and 76.0 mg/liter were observed for the 15, 30, and 60 mg/kg doses, respectively. Nonlinear least squares regression of all data sets, using a 1/y weight, indicated that zidovudine disposition was best described by a one-compartment open model with first-order absorption, where appropriate, and first-order elimination. The mean elimination half-life values ranged from 17.3 to 19.9 min for the three intravenous doses and from 16.5 to 21.9 min for the three oral doses. The mean values for the apparent volume of distribution (Vd) ranged from 0.8 to 1.0 liter/kg following oral and intravenous administration. There were no significant differences in Vd between the oral and intravenous groups. The mean total body clearance values ranged from 28.9 to 34.3 ml/min/kg following intravenous administration.(ABSTRACT TRUNCATED AT 250 WORDS)