Pharmacokinetics and Bioavailability of Terbinafine Hydrochloride Capsules in Beagle Dogs

To study the pharmacokinetics and biavailibility of terbinafine hydrochloride capsules in beagle dogs, a single intravenous (i.v.) and oral(p.o.) administration of terbinafine at a dosage of 10 mg·kg^-1 was performed in eight healthy beagles according to a two-period crossover design. Plasma concentrations of terbinafine were determined by a reverse phase high performance liquid chromatographic method. The pharmacokinetic parameters were calculated by noncompartmental analysis with WinNonlin 5.2.1 software. After intravenous administration, the main pharmacokinetic parameters were as follows: AUC_0-∞ =(5.47±1.03) μg·mL^-1·h, V_ss =(2.55±0.89) L·kg^-1, CL=(1.88±0.33) L·h^-1·kg^-1, t_1/2 =(3.02±1.70) h; whereas after oral dosing, the main pharmacokinetic parameters were as follows: t_max =(1.09±0.37) h, C_max =（0.39±0.04）μg·mL^-1, AUC_0-∞ =(0.67±0.18) μg·mL^-1·h, V_d/F =(35.17±6.58) L·kg^-1,t_1/2 =(1.69±0.74) h. The absolute bioavailibilty(/F) of terbinafine hydrochloride capsules after oral administrtion was (12.54±3.43)%.Terbinafine was absorbed and eliminated rapidly in beagles and the absolute bioavailability was very low.