期刊
JOURNAL OF PHARMACEUTICAL SCIENCES
卷 98, 期 12, 页码 4928-4940出版社
ELSEVIER SCIENCE INC
DOI: 10.1002/jps.21770
关键词
ADME; P-glycoprotein; transporters; distribution; pharamcokinetics; pharmacodynamics
资金
- University of Maryland
- Egyptian Ministry of Higher Education
Conclusions based on either in vitro or in vivo approach to evaluate the P-gp affinity status of opioids may be misleading. For example, in vitro studies indicated that fentanyl is a P-gp inhibitor while in vivo studies indicated that it is a P-gP substrate. Quite the opposite was evident for meperidine. The objective of this study was to evaluate the P-gp affinity status of methadone, buprenorphine and diprenorphine to predict P-gp-mediated drug-drug interactions and to determine a better candidate for management of opioid dependence. Two in vitro (P-gp ATPase and monolayer efflux) assays and two in vivo (tissue distribution and antinociceptive evaluation in mdr1a/b (-/-) mice) assays were used. Methadone stimulated the P-gP ATPase activity only at higher concentrations, while verapamil and GF120918 inhibited its efflux (p < 0.05). The brain distribution and antinociceptive activity of methadone were enhanced (p < 0.05) in P-gp knockout mice. Conversely, buprenorphine and diprenorphine were negative in all assays. P-gp can affect the PK/PD of methadone, but not buprenorphine or diprenorphine. Our report is in favor of buprenorphine over methadone for management of opioid dependence. Buprenorphine most likely is not a P-gP substrate and concerns regarding P-gp-mediated drug-drug interaction are not expected. (C) 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:4928-4940, 2009
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据