Pharmacokinetics of zidovudine in cats.
OBJECTIVE
To characterize the pharmacokinetics of zidovudine (AZT) in cats.


METHODS
6 sexually intact 9-month-old barrier-reared domestic shorthair cats.


METHODS
Cats were randomly alloted into 3 groups, and zidovudine (25 mg/kg) was administered i.v., intragastrically (i.g.), and p.o. 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 i.g. and p.o. routes. Area under the curve (AUC) and terminal phase half-life (t(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 i.v., i.g., and p.o. 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 i.g. administration (0.22 hours) was significantly shorter than Tmax for p.o. administration (0.67 hours). The AUC after i.v. and p.o. administration was 64.7 +/- 16.6 mg x h/L and 60.5 +/- 17.0 mg x h/L, respectively, whereas AUC for the i.g. route was significantly less at 42.5 +/- 9.41 mg x h/L. Zidovudine was well absorbed after i.g. and p.o. administration with bioavailability values of 70 +/- 24% and 95 +/- 23%, respectively.


CONCLUSIONS
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% (0.07 microM [0.019 microg/mL] for wild-type FIV clinical isolate) for at least 12 hours after i.v., i.g., or p.o. administration.
Zhang
Weijiang
W
Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, GA 30602-7390, USA.
Mauldin
Jeffrey K
JK
Schmiedt
Chad W
CW
Brockus
Charles W
CW
Boudinot
F Douglas
FD
McCrackin Stevenson
M A
MA
D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D002415:Cats / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D007275:Injections, Intravenous; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D013997:Time Factors; D015215:Zidovudine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
D018894:Reverse Transcriptase Inhibitors; D015215:Zidovudine