克霉舒搽剂中水杨酸和盐酸特比萘芬兔体透皮吸收的药动学研究

Pharmacokinetics Study of Salicylic Acid and Terbinafine Hydrochloride in Kemeishu Liniment after Percutaneous Absorption in Rabbits

目的建立盐酸特比萘芬和水杨酸兔血浆浓度的高效液相色谱测定方法,研究家兔涂擦克霉舒搽剂后其主药盐酸特比萘芬和水杨酸在兔体透皮吸收的药动学。方法 12只家兔背部去毛,随机分为单次给药高、中、低剂量组。给药前后按设定的时间耳静脉采血,采用HPLC测定盐酸特比萘芬和水杨酸的血浆浓度,利用PKS1.0软件计算主要药动学参数。结果各给药组家兔血浆中均未测得盐酸特比萘芬;单次给药低、中、高剂量组,水杨酸的主要药动学参数如下:T_(max)为(2.73±0.30),(3.48±0.16),(5.86±1.72)h,C_(max)为(25.24±9.21),(25.32±11.05),(37.47±4.31)μg·mL^(-1),T_(1/2)为(5.74±3.29),(4.60±1.99),(13.28±3.84)h。高剂量组的T_(max)、C_(max)、T_(1/2)高于中、低剂量组(P<0.05)。结论本实验建立的HPLC灵敏准确、简便易行,适合用于盐酸特比萘芬和水杨酸血浆样品的测定。克霉舒搽剂皮肤局部给药安全,盐酸特比萘芬几乎不进入到血浆中,水杨酸可小部分进入血浆中,动力学行为符合一室模型。

OBJECTIVE To establish HPLC methods for determining salicylic acid and terbinafine hydrochloride in rabbits plasma, and to investigate the pharmacokinetics of salicylic acid and terbinafinie hydrochloride in Kemeishu liniment after percutaneous absorption in rabbits. METHODS 12 rabbits with their hair on the back removed were randomized divided into large single dose group, medium single dose group and low single dose group. Plasma samples were collected and quantitated by HPLC. The pharmacokinetic parameters were calculated using PKSI.0 software. RESULTS Terbinafine hydrochloride were not determined in rabibits plasma.The main pharmacokinetics parameter of salicylic acid in low, medium and large single dose group were as follows： Tmax （2.73±0.30）, （3.48±0.16）, （5.86±1.72）h, Cmax （25.24±9.21）, （25.32±11.05）, （37.47±4.31）μg.mL^-1, T1/2 （5.74±3.29）, （4.60±1.99）, （13.28±3.84）h. The Tmax, Cmax, T1/2 in large single dose group were higher than that in medium and low single dose group （P〈0.05）. CONCLUSION The established methods are sensitive, fast and accurate, which were suitable for the determination of salicylic acid and terbinafine hydrochloride in plasma. Kemeishu liniment is safety spreding on skin, terbinafine hydrochloride seldomly can enter in the blood, salicylic acid partially enter in the blood, its pharmacokinetics fitted one-compartment model.