COMPARATIVE PHARMACOKINETICS OF 3'-AZIDO-3'-DEOXYTHYMIDINE (AZT) AND 3'-AZIDO-2', 3'-DIDEOXYURIDINE (AZDDU) IN MICE

Abstract

The pharmacokinetics of 3''azido-3''deoxythymidine (AZT) and 3''-azido-2'',3''-dideoxyuridine (AZddU, CS-87), active anti-HIV compounds, were characterized in uninfected mice. Sensitive and specific HPLC techniques were used to quantitate AZT and AZddU concentrations in serum and brain homogenates following iv doses of 50 mg/kg and 250 mg/kg. The pharmacokinetic parameters of t1/2, Clt, and Vss were similar for both compounds at each dose; however, Clt and Vss decreases at the higher dose, indicating a dose dependency. At the 50 mg/kg doses, the Clt of AZddU and AZT was 1.27 liters/hr/kg and 1.38 liters/hr/kg, respectively, which is analogous to the clearance value of AZT observed in humans. Brain/serum concentration ratios for AZddU tended to be greater than those obtained for AZT and were significantly different at the 50 mg/kg dose, being 0.234 .+-. 0.282 for AZddU and 0.064 .+-. 0.025 for AZT.