Pharmacokinetics of lamivudine in cats
Zhang, W; Mauldin, JK; Schmiedt, CW; Brockus, CW; Boudinot, FD; Stevenson, MAM
Published in: American Journal of Veterinary Research
—To characterize the pharmacokinetics of
lamivudine (3TC) in cats. —6 sexually intact 9-month-old barrier-reared
domestic shorthair cats. —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
(C), time to reach C (T), 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. —Plasma concentrations of lamivudine
declined rapidly with a t 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 T
for IG administration (0.5 hours) was significantly
shorter than T 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. —Cats had a
shorter t 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.
( 2004;65:841–846)
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