Abstract
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.
Footnotes
- Abbreviations used are::
- MET
- methadone
- P-gp
- P-glycoprotein
- Rh123
- rhodamine123
- A and B chambers
- apical and basolateral chambers, respectively
- Received November 17, 2000.
- Accepted April 11, 2001.
- The American Society for Pharmacology and Experimental Therapeutics
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