BINDING OF D-METHADONE, L-METHADONE, AND DL-METHADONE TO PROTEINS IN PLASMA OF HEALTHY-VOLUNTEERS - ROLE OF THE VARIANTS OF ALPHA-1-ACID GLYCOPROTEIN

The plasma concentrations of α1-acid glycoprotein (AAG), albumin, triglycerides, cholesterol, and total proteins, as well as the plasma binding of racemic, d-methadone, and 1-methadone were measured in 45 healthy subjects. The AAG phenotypes and the concentrations of AAG variants were also determined. The measured free fractions for racemic, d-methadone, and 1-methadone were, respectively, 12.7% ± 3.3%, 10.0% ± 2.9%, and 14.2% ± 3.2% (mean ± SD). A significant correlation was obtained between the binding ratio (B/F) for dl-methadone and the total AAG concentration (r = 0.724;p < 0.001). A multiple stepwise regression analysis showed that AAG was the main explanatory variable for the binding of the racemate. When concentrations of AAG variants were considered, a significant correlation was obtained between the binding ratio of dl-methadone and orosomucoid2 A concentration (r = 0.715; p < 0.001), a weak correlation between dl-methadone and orosomucoidl S concentration (r = 0.494; p < 0.001), and no correlation between dl-methadone and orosomucoidl F1 concentration (r = 0.049; not significant).Similar findings were obtained with the enantiomers. This study shows the importance of considering not only total AAG but also concentrations of AAG variants when measuring the binding of methadone and possibly of other drugs in plasma. © 1990.