狗胰液中丝裂霉素的药物穿透动力学研究

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

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～ 2 4 0min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tmax和cmax分别为 ( 0 .3 6± 0 .1 6)h和 ( 65 .6± 75 .8) μg·L-1;丝裂霉素血浆及胰液t1/ 2 β分别为 ( 1 .1 7± 0 .96)h和 ( 0 .71± 0 .66)h ,AUC0～∞ 分别为 ( 1 0 7.9± 4 3 .9) μg·h·L-1和 ( 3 3 .5±2 8.8) 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 .0 1 ) ;其胰液通透指数 (PI)平均为 0 .3 1± 0 .1 9。

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 -1 for pancreatic juice, t 1/2 β were ( 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).