盐酸特比萘芬成膜给药系统皮肤药动学探索性研究

Exploratory Research on Dermato-pharmacokinetics of Terbinafine Hydrochloride Film-forming System

以巴马小香猪为动物模型,利用胶带剥离法对自制盐酸特比萘芬成膜给药系统和其市售参比制剂(1%盐酸特比萘芬涂膜剂)的皮肤药动学进行了初步探索。建立了高效液相色谱法和液质联用法,分别用于测定给药0~7 d和7~14 d剥离下来的猪皮角质层中的药物浓度。结果显示,自制盐酸特比萘芬成膜给药系统与参比制剂的主要皮肤药动学参数无显著性差异(P>0.05)。自制与参比制剂的c_(max)为(14603.95±1461.59)和(14542.08±1481.07)ng/cm^(2),t 1/2为(75.84±22.35)和(68.34±3.41)h,AUC_(0→t)为(920447.88±166949.76)和(901108.6±141669.28)ng·cm^(–2)·h;二者t_(max)均为3 h。自制盐酸特比萘芬成膜给药系统的相对生物利用度为(102.15±15.13)%。

Taking BAMA piglet as the experimental animal model,the dermato-pharmacokinetic properties of terbinafine hydrochloride film-forming system and the commercially available product(1%terbinafine hydrochloride cutaneous solution)were preliminarily investigated by the tape stripping method.An HPLC and a LC/MS were established for determination of drug concentration in the stratum corneum peeled off from the piglet skin on days 0-7 and days 7-14 after administration,respectively.The results showed that there were no significant differences between the self-made and reference preparations in main pharmacokinetic parameters(P>0.05).The values of c_(max),t_(1/2) and AUC_(0→t) for the self-made and reference preparations were(14603.95±1461.59)and(14542.08±1481.07)ng/cm^(2),(75.84±22.35)and(68.34±3.41)h,(920447.88±166949.76)and(901108.6±141669.28)ng·cm^(–2)·h,respectively.The values of t_(max) for both preparations were 3 h.The relative bioavailability of the self-made preparation was(102.15±15.13)%.