Nussio Matthew R, Sykes Matthew J, Miners John O, Shapter Joseph G
School of Chemistry, Physics and Earth Sciences, and Department of Clinical Pharmacology, Flinders University, Sturt Road, Bedford Park, Adelaide, SA 5001, Australia.
Langmuir. 2009 Jan 20;25(2):1086-90. doi: 10.1021/la803288s.
Drug-membrane interactions assume considerable importance in pharmacokinetics and drug metabolism. Here, we present the interaction of chlorpromazine hydrochloride (CPZ) with supported phospholipid bilayers. It was demonstrated that CPZ binds rapidly to phospholipid bilayers, disturbing the molecular ordering of the phospholipids. These interactions were observed to follow first order kinetics, with an activation energy of approximately 420 kJ mol(-1). Time-dependent membrane disruption was also observed for the interaction with CPZ, such that holes appeared in the phospholipid bilayer after the interaction of CPZ. For this process of membrane disruption, "lag-burst" kinetics was demonstrated.
药物与膜的相互作用在药代动力学和药物代谢中具有相当重要的意义。在此，我们展示了盐酸氯丙嗪（CPZ）与支持的磷脂双层的相互作用。结果表明，CPZ能迅速与磷脂双层结合，扰乱磷脂的分子排列。观察到这些相互作用遵循一级动力学，活化能约为420 kJ mol(-1)。与CPZ相互作用时还观察到时间依赖性的膜破坏，即CPZ相互作用后磷脂双层中出现孔洞。对于这种膜破坏过程，证明了“滞后-爆发”动力学。
