Methadone plasma protein binding: Alterations in cancer and displacement from α1-acid glycoprotein

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Abstract
Because of their elevated concentrations of plasma .alpha.1-acid glycoprotein (AAG), cancer patients had a lower free fraction of methadone in plasma than did members of a control group. This difference was not great (-20%), but there was a 4-fold variation in free fraction among a group of 13 patients (0.064-0.23). The bound/free methadone concentration ratio correlated linearly with plasma AAG. The binding of methadone to AAG was characterized by 2 classes of binding sites, the more avid having an association constant [Ka] of 4 .times. 105 M-1 and an N of 0.38. Methadone could be displaced from AAG binding sites by a number of drugs: propranolol, chlorpromazine, prochlorperazine, thioridazine and imipramine. The concentrations required for significant displacement (27 .mu.M), as well as the relatively low Ka for methadone, suggest that the free fraction of methadone will not be significantly affected by elevated methadone concentrations or through displacement by other drugs that also bind to AAG.