Wang Shu-Rong, Chen Yu, Wu Li-Ping, Miao Wen-Juan, Xiong Mei-Jin, Chen Cong, Zhong Zhi-Rong, Ye Li-Ming
Department of Pharmacy, the Affiliated Hospital of Luzhou Medical College, Luzhou 646000, PR China.
J Pharm Biomed Anal. 2008 Jan 22;46(2):243-9. doi: 10.1016/j.jpba.2007.09.024. Epub 2007 Sep 29.
Biological fluid cell membranes are barriers for the uptake of many kinds of drugs and their metabolites, along with passive transport across membranes and bioaccumulation. Biopartitioning micellar chromatography (BMC) is a mode of micellar liquid chromatography that uses micellar mobile phases of Brij35 under adequate experimental conditions and can be useful to simulate the drug's passive absorption and the transport in biological systems. The use of micellar aqueous solutions of Brij35 as mobile phases in reversed-phase liquid chromatography has proven to be valid to predict the biological activities of barbiturates, benzodiazepines, catecholamines, local anesthetics, non-steriodal anti-inflammatory drugs and tricyclic antidepressants. In this study, the relationships between the capacity factor in BMC and some pharmacokinetic and pharmacodynamic parameters of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors are studied. Predictive quantitative retention-activity relationship (QRAR) models describing some of the biological activities and pharmacokinetic properties of HMG-CoA reductase inhibitors are obtained. The results indicate that QRAR model may be a useful tool during the drug discovery process.
生物流体细胞膜是多种药物及其代谢产物摄取的屏障，同时存在跨膜被动转运和生物蓄积现象。生物分配胶束色谱法（BMC）是胶束液相色谱的一种模式，在适当的实验条件下使用Brij35胶束流动相，可用于模拟药物在生物系统中的被动吸收和转运。在反相液相色谱中使用Brij35胶束水溶液作为流动相已被证明可有效预测巴比妥类药物、苯二氮䓬类药物、儿茶酚胺类药物、局部麻醉药、非甾体抗炎药和三环类抗抑郁药的生物活性。在本研究中，研究了BMC中的容量因子与3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶抑制剂的一些药代动力学和药效学参数之间的关系。获得了描述HMG-CoA还原酶抑制剂某些生物活性和药代动力学性质的预测性定量保留-活性关系（QRAR）模型。结果表明，QRAR模型可能是药物发现过程中的一个有用工具。
