Pharmacokinetics of (—)-β-L-2′,3′-Dideoxy-3′-thiacytidine in Rats

Abstract

(—)-β-L-2′,3′-Dideoxy-3′-thiacytidine (3TC) has been shown to be a potent and selective inhibitor of human immunodeficiency virus (HIV) types 1 and 2 and of hepatitis B virus (HBV) in-vitro and in man. In this study, a reversed-phase high-performance liquid-chromatographic (HPLC) analytical method was developed and the pharmacokinetics of 3TC were characterized in the rat. Five adult male Sprague-Dawley rats were administered 30 mg kg−1 3TC by intravenous bolus injection. Plasma and urine concentrations of 3TC were determined by HPLC. Pharmacokinetic parameters were generated using area/moment analysis. Plasma 3TC concentrations declined in a biexponential manner with a terminal phase half-life of 0·96 ± 0·35 h (mean ± s.d.). The mean total, renal and non-renal clearances of 3TC were 1·38 ± 0·20, 1·06 ± 0·29 and 0·32 ± 0·12 L h−1 kg−1, respectively. An average of 75 ± 11% of the administered dose was eliminated as unchanged 3TC in the urine. The steady-state volume of distribution of 3TC averaged 1·29 ± 0·30 L kg−1. Although differences in the pharmacokinetics of cytidine analogues were noted, the general disposition patterns of the compounds were similar.