RT Journal Article
SR Electronic
T1 Methadone Inhibits Rhodamine123 Transport in Caco-2 Cells
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 954
OP 956
VO 29
IS 7
A1 Elke Störmer
A1 Michael D. Perloff
A1 Lisa L. von Moltke
A1 David J. Greenblatt
YR 2001
UL http://dmd.aspetjournals.org/content/29/7/954.abstract
AB This study investigated the effects of racemic methadone (MET) on P-glycoprotein (P-gp) activity in cell culture. MET showed no differential rates of passage between the basolateral to apical (B to A) and apical to basolateral (A to B) direction across Caco-2 cell monolayers in a transwell system. MET transport in either direction was not importantly influenced by the P-gp inhibitor verapamil. However, MET was a potent inhibitor (IC50 = 7.5 μM) of rhodamine123 B to A transport across Caco-2 cell monolayers, causing a reduction to 25% of control at 100 μM MET. In this model of Caco-2 monolayers, rates of MET passage between B to A and A to B directions could not be distinguished. However, MET can inhibit P-gp activity at intraluminal concentrations that might be achieved clinically. This may lead to increased bioavailability of coadministered compounds. The American Society for Pharmacology and Experimental Therapeutics