狗胰液中丝裂霉素的药物穿透动力学研究

 目的:利用动物(狗)探讨丝裂霉素对胰腺组织的动态穿透行为。方法:6只杂种狗,胰腺导管引流术后静脉给予丝裂霉素,动态采集并测定0～240min内血浆及胰液中药物浓度,利用PCNONLIN程序进行其动力学模型和参数分析及统计学判定。结果:丝裂霉素在血浆及胰液中均符合二室开放模型;胰液中药物t_max和c_max分别为(0.36±0.16)h和(65.6±75.8)μg·L^-1;丝裂霉素血浆及胰液t_1/2β分别为(1.17±0.96)h和(0.71±0.66)h,AUC_0～∞分别为(107.9±43.9)μg·h·L^-1和(33.5±28.8)μg·h·L^-1。结论:丝裂霉素静注后很快进入胰液,但其药物水平始终低于血浆,且胰液中药物消除略快于血浆(P<0.01);其胰液通透指数(PI)平均为0.31±0.19。

Study on pharmacokinetics of mitomycin C penetrated into the pancreatic juice in dogs

OBJECTIVE:To study on the pharmacokinetics of Mitomycin C (MMC) penetrated into the pancereatic juice.METHODS:6 mongrel dogs following 2 mg single dose by intravenous injection were enrolled after operated pancreatico drainage tube by surgery.MMC concentrations in plasma and pancreatic juice were determined by using a rapid and sensitive RP-HPLC assay.Pharmacokinetic behavious of MMC in plasma and pancreatic juice were analysed by using computer program PCNONLIN (SCI,v.4.2).RESULTS:PK of MMC in plasma and pancreatic juice were compatible with a two-compartment open model.Pharmacokinetic parameters in plasma and pancreatic juice were t_max=(0.36±0.16)h and c_max=(65.6±75.8)μg·L^{-1for pancreatic juice,t_1/2βwere(1.17±0.96)h and (0.71±0.66)h,and AUC_0～∞(107.9±43.9)μg·h·L-1 and (33.5±28.8)μg·h·L-1,respectively.CONCLUSION:MMC penetrated rapidly into pancreatic juice after iv,and was eliminated fast from pancrease than plasma (P<0.01).The mean penetration index (PI) of MMC was (0.31±0.19).}