复方樟柳碱注射液在家兔体内的药代动力学及组织分布研究

Pharmacokinetics and tissue distribution of compound anisodine in rabbits

目的研究复方樟柳碱(CA)在家兔体内的药代动力学及组织分布特征。方法家兔颞浅动脉旁皮下注射0.7 mL·kg^(-1)复方樟柳碱注射液,用LC-MS/MS法测定氢溴酸樟柳碱及盐酸普鲁卡因在家兔血浆及组织中的浓度,用Win Nonlin 6.2软件计算药代动力学参数。结果氢溴酸樟柳碱和盐酸普鲁卡因的主要药代动力学参数如下:C_(max)分别为(12.93±1.90),(895.47±213.99)ng·mL^(-1);t_(max)分别为(0.35±0.18),(0.24±0.15)h;t_(1/2)分别为(0.82±0.22),(0.49±0.11)h;AUC_(0-t)分别为(19.20±5.71),(706.59±121.90)ng·mL^(-1)·h。氢溴酸樟柳碱在视网膜、脉络膜,肾及肺中分布较高,盐酸普鲁卡因在视网膜、脉络膜、脾及肾中分布较高。结论复方樟柳碱注射液颞浅动脉旁皮下注射给药后吸收快,消除半衰期短,组织分布广泛。

Objective To study the pharmacokinetics and tissue distri- bution characteristics of compound anisodine （CA） in rabbits. Methods Rabbits were injected with 0.7 mL · kg^-1 CA subcutaneously around superficial temporal artery, and LC -MS/MS method was used to deter- mine the concentration of anisodine hydrobromide and procaine hydro-chloride in plasma and tissues. The pharmacokinetic parameters were calculated by WinNonlin 6.2 software. Results Main pharmacokinetic parameters of anisodine and procaine were as follows： Cmax were （ 12. 93 ± 1.90）, （895.47 ±213.99）ng ·mL^-1 ; tmax were （0. 35 ±0. 18）, （0.24±0. 15）h; t1/2were （0.82 ±0.22）, （0.49 ±0. 11）h; AUC0-t were （ 19.20 ±5.71 ）, （706.59 ± 121.90）ng ·mL^-1 h, respectively. The concentration of anisodine was higher in the retina and choroid, kidney, and lung, and procaine was distributed more in the retina and choroid, spleen, and kidney. Conclusion CA are rapidly absorbed with short half-life and extensive distribution.