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药物与乳糜微粒的结合率可表示药物淋巴转运倾向。测定了5种模型药物(卤泛群、灰黄霉素、桂利嗪、辛伐他汀和洛伐他汀)与乳糜微粒的结合率及其在长链甘油三酯中的溶解度。以偏最小二乘回归(PLS)分析建立了乳糜微粒结合率与药物分子理化参数的线性关系。得到各理化参数对药物与乳糜微粒结合的影响大小依次为:极性表面积(PSA)>氢键受体数(HBA)>氢键供体数(HBD)>长链甘油三酯中溶解度(SLCT)>熔点(mp)>表观油水分配系数(logP)>pH 7.4时表观油水分配系数(logD)>自由旋转键(FRB)>分子体积(MV)>分子量(MW)>密度,其中SLCT、logP、logD和密度起正向变化作用,其他理化性质起负向变化作用。药物分子各理化参数中,PSA、HBA、HBD及SLCT对预测药物的淋巴转运可能起较大作用。
Drugs and chylomicron binding rate can be expressed drug lymphatic transit tendency. The binding rates of the five model drugs (halofantrine, griseofulvin, cinnarizine, simvastatin and lovastatin) to chylomicrons and their solubility in long-chain triglycerides were determined. The linear relationship between chylomicron binding rate and drug molecular physicochemical parameters was established by partial least squares regression (PLS) analysis. The influence of different physical and chemical parameters on the binding of chylomicrons to drugs was investigated. The order of polarity was: PSA> HBA> HBD> Solubility in long chain triglycerides (SLCT )> Mp> apparent oil-water partition coefficient (logP)> apparent oil-water partition coefficient (logD)> free rotation key (FRB)> molecular weight (MV)> molecular weight (MW)> density at pH 7.4, , LogP, logD and density play a positive role in the change, other physical and chemical properties play a negative change. Among the physicochemical parameters of drug molecules, PSA, HBA, HBD and SLCT may play a significant role in predicting the lymphatic transport of drugs.