Interaction of drugs of abuse and maintenance treatments with human P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2). Export

@article{citeulike:6080974, abstract = {Drug interaction with P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) may influence its tissue disposition including blood-brain barrier transport and result in potent drug-drug interactions. The limited data obtained using in-vitro models indicate that methadone, buprenorphine, and cannabinoids may interact with human P-gp; but almost nothing is known about drugs of abuse and BCRP. We used in vitro P-gp and BCRP inhibition flow cytometric assays with hMDR1- and hBCRP-transfected HEK293 cells to test 14 compounds or metabolites frequently involved in addiction, including buprenorphine, norbuprenorphine, methadone, ibogaine, cocaine, cocaethylene, amphetamine, N-methyl-3,4-methylenedioxyamphetamine, 3,4-methylenedioxyamphetamine, nicotine, ketamine, Delta9-tetrahydrocannabinol (THC), naloxone, and morphine. Drugs that in vitro inhibited P-gp or BCRP were tested in hMDR1- and hBCRP-MDCKII bidirectional transport studies. Human P-gp was significantly inhibited in a concentration-dependent manner by norbuprenorphine>buprenorphine>methadone>ibogaine and THC. Similarly, BCRP was inhibited by buprenorphine>norbuprenorphine>ibogaine and THC. None of the other tested compounds inhibited either transporter, even at high concentration (100 mum). Norbuprenorphine (transport efflux ratio 11) and methadone (transport efflux ratio 1.9) transport was P-gp-mediated; however, with no significant stereo-selectivity regarding methadone enantiomers. BCRP did not transport any of the tested compounds. However, the clinical significance of the interaction of norbuprenorphine with P-gp remains to be evaluated.}, author = {Tournier, Nicolas and Chevillard, Lucie and Megarbane, Bruno and Pirnay, St\'{e}phane and Scherrmann, Jean-Michel M. and Decl\`{e}ves, Xavier}, citeulike-article-id = {6080974}, citeulike-linkout-0 = {http://dx.doi.org/10.1017/S1461145709990848}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/19887017}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=19887017}, day = {4}, doi = {10.1017/S1461145709990848}, issn = {1469-5111}, journal = {The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP)}, keywords = {iliad}, month = {November}, pages = {1--11}, posted-at = {2009-11-06 14:22:12}, priority = {2}, title = {Interaction of drugs of abuse and maintenance treatments with human P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2).}, url = {http://dx.doi.org/10.1017/S1461145709990848}, year = {2009} }

TY - JOUR ID - citeulike:6080974 L3 - citeulike-article-id:6080974 N2 - Drug interaction with P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) may influence its tissue disposition including blood-brain barrier transport and result in potent drug-drug interactions. The limited data obtained using in-vitro models indicate that methadone, buprenorphine, and cannabinoids may interact with human P-gp; but almost nothing is known about drugs of abuse and BCRP. We used in vitro P-gp and BCRP inhibition flow cytometric assays with hMDR1- and hBCRP-transfected HEK293 cells to test 14 compounds or metabolites frequently involved in addiction, including buprenorphine, norbuprenorphine, methadone, ibogaine, cocaine, cocaethylene, amphetamine, N-methyl-3,4-methylenedioxyamphetamine, 3,4-methylenedioxyamphetamine, nicotine, ketamine, Delta9-tetrahydrocannabinol (THC), naloxone, and morphine. Drugs that in vitro inhibited P-gp or BCRP were tested in hMDR1- and hBCRP-MDCKII bidirectional transport studies. Human P-gp was significantly inhibited in a concentration-dependent manner by norbuprenorphine>buprenorphine>methadone>ibogaine and THC. Similarly, BCRP was inhibited by buprenorphine>norbuprenorphine>ibogaine and THC. None of the other tested compounds inhibited either transporter, even at high concentration (100 mum). Norbuprenorphine (transport efflux ratio 11) and methadone (transport efflux ratio 1.9) transport was P-gp-mediated; however, with no significant stereo-selectivity regarding methadone enantiomers. BCRP did not transport any of the tested compounds. However, the clinical significance of the interaction of norbuprenorphine with P-gp remains to be evaluated. JF - The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP) SN - 1469-5111 EP - 11 TI - Interaction of drugs of abuse and maintenance treatments with human P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2). SP - 1 KW - iliad AU - Tournier, Nicolas AU - Chevillard, Lucie AU - Megarbane, Bruno AU - Pirnay, Stéphane AU - Scherrmann, Jean-Michel AU - Declèves, Xavier PY - 2009/11/04/ UR - http://dx.doi.org/10.1017/S1461145709990848 ER -