Pharmacokinetics of zidovudine in cats

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 (C-max), time to reach C-max (T-max) and bioavailability were compared between IG and PO routes. Area under the curve (AUC) and terminal phase half-life f(1/2) among the 3 administration routes were also compared. Results-Plasma concentrations of zidovudine declined rapidly with t(1/2) 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 T-max for IG administration (0.22 hours) was significantly shorter than T-max 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. Ziclovudine 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% (0.07muM [0.019 mug/mL] for wild-type FIV clinical isolate) for at least 1 hours after IV, IG, or PO administration.