PT  - JOURNAL ARTICLE
AU  - Elke Störmer
AU  - Michael D. Perloff
AU  - Lisa L. von Moltke
AU  - David J. Greenblatt
TI  - Methadone Inhibits Rhodamine123 Transport in Caco-2 Cells
DP  - 2001 Jul 01
TA  - Drug Metabolism and Disposition
PG  - 954--956
VI  - 29
IP  - 7
4099  - http://dmd.aspetjournals.org/content/29/7/954.short
4100  - http://dmd.aspetjournals.org/content/29/7/954.full
SO  - Drug Metab Dispos2001 Jul 01; 29
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