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

    • 摘要: 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.

       

      Abstract: 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: 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; whereas after oral dosing, the main pharmacokinetic parameters were as follows: 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. 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.

       

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