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

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(10mg·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菲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:tmas=(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 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, Vas = (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.