Pharmacokinetics of lamivudine in cats.
OBJECTIVE
To characterize the pharmacokinetics of lamivudine (3TC) in cats.


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


METHODS
Cats were randomly alloted into 3 groups, and lamivudine (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 lamivudine 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 lamivudine declined rapidly with a t(1/2) of 1.9 +/- 0.21 hours, 2.6 +/- 0.66 hours, and 2.7 +/- 1.50 hours after i.v., i.g., and p.o. 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 i.g. administration (0.5 hours) was significantly shorter than Tmax for p.o. administration (1.1 hours). The AUC after i.v., i.g., and p.o. administration was 130 +/- 55.2 mg x h/L, 115 +/- 97.5 mg x h/L, and 106 +/- 94.9 mg x h/L, respectively. Lamivudine was well absorbed after i.g. and p.o. administration with bioavailability values of 88 +/- 45% and 80 +/- 52%, respectively.


CONCLUSIONS
Cats had a shorter t(1/2) 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% (0.14 microM [0.032 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
SM
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; D019259:Lamivudine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D013997:Time Factors
D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine