Methadone inhibits rhodamine123 transport in Caco-2 cells.

E Störmer, M D Perloff, L L von Moltke, D J Greenblatt

Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, Massachusetts 02111, USA.

Drug metabolism and disposition: the biological fate of chemicals 2001 Jul

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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 (IC(50) = 7.5 microM) of rhodamine123 B to A transport across Caco-2 cell monolayers, causing a reduction to 25% of control at 100 microM 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.

Citation

E Störmer, M D Perloff, L L von Moltke, D J Greenblatt. Methadone inhibits rhodamine123 transport in Caco-2 cells. Drug metabolism and disposition: the biological fate of chemicals. 2001 Jul;29(7):954-6