Objective—To characterize the pharmacokinetics of zidovudine (AZT) in cats.
Animals—6 sexually intact 9-month-old barrier-reared domestic shorthair cats.
Procedure—Cats were randomly alloted into 3 groups, and zidovudine (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 zidovudine 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 zidovudine declined rapidly with t½ of 1.4 ± 0.19 hours, 1.4 ± 0.16 hours, and 1.5 ± 0.28 hours after IV, IG, and PO administration, respectively. Total body clearance and steady-state volume of distribution were 0.41 ± 0.10 L/h/kg and 0.82 ± 0.15 L/kg, respectively. Mean Tmax for IG administration (0.22 hours) was significantly shorter than Tmax for PO administration (0.67 hours). The AUC after IV and PO administration was 64.7 ± 16.6 mg·h/L and 60.5 ± 17.0 mg·h/L, respectively, whereas AUC for the IG route was significantly less at 42.5 ± 9.41 mg·h/L. Zidovudine was well absorbed after IG and PO administration with bioavailability values of 70 ± 24% and 95 ± 23%, respectively.
Conclusions and Clinical Relevance—Cats had slower clearance of zidovudine, compared with other species. Plasma concentrations of zidovudine were maintained above the minimum effective concentration for inhibiting FIV replication by 50% (0.07µM [0.019 µg/mL] for wild-type FIV clinical isolate) for at least 12 hours after IV, IG, or PO administration. (Am J Vet Res 2004;65:835–840)