Objective—To characterize the pharmacokinetics of lamivudine (3TC) in cats.
Animals—6 sexually intact 9-month-old barrier-reared domestic shorthair cats.
Procedure—Cats were randomly alloted into 3 groups, and lamivudine (25 mg/kg) was administered IV, intragastrically (IG), and PO in a 3-way crossover study design with 2-week washout periods between experiments. Plasma samples were collected for 12 hours after drug administration, and lamivudine concentrations were determined by high-performance liquid chromatography. Maximum plasma concentrations (Cmax), time to reach Cmax (Tmax), and bioavailability were compared between IG and PO routes. Area under the curve (AUC) and terminal phase halflife (t½) among the 3 administration routes were also compared.
Results—Plasma concentrations of lamivudine declined rapidly with a t½ of 1.9 ± 0.21 hours, 2.6 ± 0.66 hours, and 2.7 ± 1.50 hours after IV, IG, and PO administration, respectively. Total body clearance and steady-state volume of distribution were 0.22 ± 0.09 L/h/kg and 0.60 ± 0.22 L/kg, respectively. Mean Tmax for IG administration (0.5 hours) was significantly shorter than Tmax for PO administration (1.1 hours). The AUC after IV, IG, and PO administration was 130 ± 55.2 mg·h/L, 115 ± 97.5 mg·h/L, and 106 ± 94.9 mg·h/L, respectively. Lamivudine was well absorbed after IG and PO administration with bioavailability values of 88 ± 45% and 80 ± 52%, respectively.
Conclusions and Clinical Relevance—Cats had a shorter t½ but slower total clearance of lamivudine, compared with humans. Plasma concentrations of lamivudine were maintained above the minimum effective concentration for inhibiting FIV replication by 50% (0.14µM [0.032 µg/mL] for wild-type FIV clinical isolate) for at least 12 hours after IV, IG, or PO administration. (Am J Vet Res 2004;65:841–846)