盐酸特比萘芬胶囊在比格犬体内的药物动力学及生物利用度研究

Pharmacokinetics and Bioavailability of Terbinafine Hydrochloride Capsules in Beagle Dogs

为了研究盐酸特比萘芬胶囊在比格犬体内的药物动力学(简称药动学)特征及生物利用度,选用健康比格犬8只,进行单剂量(10 mg·kg-1)静脉注射特比萘芬注射液和口服盐酸特比萘芬胶囊,采用双周期随机交叉试验设计,用反相高效液相色谱法测定血药质量浓度,利用Winnolin 5.2.1非房室模型计算各药动学参数.结果表明,静注盐酸特比萘芬主要药动学参数为:AUC0-∞=(5.47±1.03)μg·mL-1·h,Vss=(2.55±0.89)L·kg-1,CL=(1.88±0.33)L·h-1·kg-1,t1/2=(3.02±1.70)h;口服盐酸特比萘芬胶囊主要药动学参数为:tmax=(1.09±0.37)h,Cmax=(0.39±0.04)μg·mL-1,AUC0-∞=(0.67±0.18)μg·mL-1·h,Vd/F=(35.17±6.58)L·kg-1,t1/2=(1.69±0.74)h.比格犬口服盐酸特比萘芬胶囊的绝对生物利用度为(12.54±3.43)%.特比萘芬在比格犬体内吸收迅速,消除快,生物利用度低.

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 con- centrations of terbinafine were determined by a reverse phase high performance liquid chromatographic method. The pharmacokinetic parameters were calculated by noneompartmental 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·k-1,t_1/2=（1.69±0.74）h. The abso- lute bioavailibihy （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.