ppi药物代谢机理及临床相互作用课件.ppt

* 16 Welage LS. The pharmacologic and pharmacokinetic basis of current and future PPIs [poster]. Presented at: American College of Gastroenterology meeting; October 14, 2000; New York, NY. 2000. 17 Nexium (埃索美拉唑 magnesium) Prescribing Information, AstraZeneca, Wilmington, Del; 2001. 16 Welage LS. The pharmacologic and pharmacokinetic basis of current and future PPIs [poster]. Presented at: American College of Gastroenterology meeting; October 14, 2000; New York, NY. 2000. 22 Spencer CM, Faulds D. 埃索美拉唑. Drugs. 2000;60:321–329. 31 Welage LS, Berardi RR. Evaluation of 奥美拉唑, 兰索拉唑, 泮托拉唑, and 雷贝拉唑 in the treatment of acid-related diseases. J Am Pharm Assoc (Wash). 2000;40:52–62. 32 Furuta T, Ohashi K, Kosuge K, et al. CYP2C19 genotype status and effect of 奥美拉唑 on intragastric pH in humans. Clin Pharmacol Ther. 1999;65:552–561. While all PPIs are substrates to some extent of CYP2C19, this does not mean they all inhibit 2C19. The ability to inhibit the enzyme is based on its affinity/binding to the metabolic enzyme. There are multiple ways to assess inhibition of drug metabolism in vitro– looking at human liver microsomes or recombinant enzyme are 2 common approaches. In general the lower the Ki indicates the low concentrations of drug inhibit the enzyme– thus as seen here OME and eso with lower Ki values indicate they are more potent inhibitors of CYP219 in vitro than panto. It is however important to recognize that in vitro students do not always predict in vivo interactions and that can be seen here in that lans appears to be a potentob inhibitor of CYP2C19 in vitro but we have not observed this in human studies. Thus, one must be careful extrapolating in vitro drug interaction data to in vivo interactions. * Over all this translates into drug the drug interactions shown here– with the green circles representing no interaction was seen in clinical studies; the ? Indicating no data is available and you can read the others– in * * * 如何抉择？