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.

Détails

ID Serval
serval:BIB_33D3B86707ED
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
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.
Périodique
Clinical Pharmacology and Therapeutics
Auteur⸱e⸱s
Eap C.B., Cuendet C., Baumann P.
ISSN
0009-9236 (Print)
ISSN-L
0009-9236
Statut éditorial
Publié
Date de publication
1990
Peer-reviewed
Oui
Volume
47
Numéro
3
Pages
338-346
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Résumé
The plasma concentrations of alpha 1-acid glycoprotein (AAG), albumin, triglycerides, cholesterol, and total proteins, as well as the plasma binding of racemic, d-methadone, and l-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 l-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 less than 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 less than 0.001), a weak correlation between dl-methadone and orosomucoid1 S concentration (r = 0.494; p less than 0.001), and no correlation between dl-methadone and orosomucoid1 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.
Mots-clé
Adult, Blood Proteins/metabolism, Cholesterol/blood, Female, Humans, Male, Methadone/metabolism, Middle Aged, Orosomucoid/genetics, Orosomucoid/metabolism, Phenotype, Protein Binding, Regression Analysis, Serum Albumin/metabolism, Stereoisomerism, Triglycerides/blood
Pubmed
Web of science
Création de la notice
01/03/2013 10:06
Dernière modification de la notice
20/08/2019 13:20
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