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目的 究氯法齐明在正常大鼠体内的药物代谢动力学及组织分布特征.方法 将平均体质量(200±20) g的Sprague-Dawley(SD)雄性大鼠按随机数字表法分成8组,每组5只.分为单次给药实验组包括空白对照组(BL)、空腹实验组(KF)、普通饮食组(NM)、高脂饮食组(HM)、低剂量组(NL)、高剂量组(NH)、中剂量组(即普通饮食组NM);多次给药实验组包括空白对照组(D0)和多次给药组(D1).单次给药实验组中低、高剂量组给药剂量分别为2.1 mg/d、12.6 mg/d,其他组均为中剂量6.3 mg/d;多次给药组剂量为2.1 mg/d.空白对照组(BL组和D0组)均以油溶剂代替药物溶液.给药后不同时间点取血及组织样本,应用液相色谱-质谱联用法(LC-MS/MS)测定氯法齐明在大鼠血浆和组织液中的药物浓度,并计算药物代谢动力学参数血药浓度-时间曲线下面积(AUC) 、峰浓度(Cmax) 、达峰时间(Tmax) 和半衰期(T1/2).结果 氯法齐明单次给药后,Cmax值HM组为(1348.05±208.46) ng/ml,明显高于NM组[(719.33±123.70) ng/ml;t=5.77,PNL,肺和脾可见轻微增大.结论 单次给药氯法齐明的药物代谢动力学特征受食物中高脂肪成分及剂量影响较大,多次给药药物浓度在血浆和组织中的分布不均具有独特性,连续给药约15 d后血浆药物浓度维持稳定低值,但组织中药物浓度继续增加.“,”Objective To explore the pharmacokinetics and tissue distribution of clofazimine (Cfz) in rats.Methods Forty Sprague-Dawley male rats at the weight of (200±20) g were randomly divided into 8 groups (n=5).Single dose groups including rats treated with blank control (BL), fasting group (KF), normal diet group (NM), high fat diet group (HM), low dose group (NL), high dose group (NH), middle dose group (normal diet group, NM);multiple dosing group including blank control group (D0) and multiple drug group (D1).Single dose groups were treated with middle dose of 6.3 mg/d, except 2.1 mg/d and 12.6 mg/d for NL and NH, respectively, and the dose of multiple-dose groups was 2.1 mg/d;while BL and D0 groups were given oil soluble liquid.Blood and tissue samples were collected at different times after single or continuous administration.Serum Cfz levels and drug tissue contents were determined by LC-MS/MS methods.Pharmacokinetic parameters (AUC, Cmax, Tmax, and T1/2) were calculated.Results With single-dose, Cmax of Cfz in NH group was significantly higher than those in NM group ((1348.05±208.46) ng/ml vs.(719.33±123.70) ng/ml;t=5.77, PNL.The spleen and lung was seen slightly increased in the size.Conclusion The pharmacokinetic characteristics of Cfz after one single dose are greatly influenced by the high fat content in food and dosage, which was unique for multiple dosing revealing drug concentration in plasma and tissue maldistribution.After continuous adminstration for about 15 days, the plasma drug concentration was kept stable at low value, but drug concentration in tissue was continue to increase causing accumulation within tissues (especially in adipose tissue) lead to coloration.