Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/42004
Citations | ||
Scopus | Web of ScienceĀ® | Altmetric |
---|---|---|
?
|
?
|
Type: | Journal article |
Title: | Lack of influence of CYP2D6 genotype on the clearance of (R)- (S)- and racemic-methadon |
Author: | Coller, J. Joergensen, C. Foster, D. James, H. Gillis, D. Christrup, L. Somogyi, A. |
Citation: | International Journal of Clinical Pharmacology and Therapeutics, 2007; 45(7):410-417 |
Publisher: | Dustri-Verlag Dr Karl Feistle |
Issue Date: | 2007 |
ISSN: | 0946-1965 |
Statement of Responsibility: | J.K. Coller, C. Joergensen, D.J.R. Foster, H. James, D. Gillis, L. Christrup and A.A. Somogyi |
Abstract: | Objective: To investigate the influence of CYP2D6 genotype on the oral clearance of (R)-, (S)- and rac-methadone. Methods: In this retrospective study, CYP2D6 genotypes were identified in 56 methadone maintained subjects. Plasma concentrations of (R)-, (S)- and rac-methadone were determined by stereoselective HPLC and sufficient data were available to estimate the apparent oral clearances of (R)-, (S)- and rac-methadone using a population kinetic model in 37 of the genotyped subjects. Results: The CYP2D6 allele frequencies were similar to those previously reported in Caucasians, the most common being: CYP2D6*1 (35.2%), CYP2D6*2 (12.0%) and CYP2D6*4 (22.2%). Three unknown SNPs were found in four subjects: 1811G > A (n = 1), 1834C > T (n = 1) and 2720G > C (n = 2). The oral clearances of (R)-, (S)- and rac-methadone varied 5.4-, 6.8- and 6.1-fold, respectively. No significant differences in methadone oral clearance were found between CYP2D6 genotypic PM, IM and EM (p = 0.57, 0.40 and 0.43 for (R)-, (S)- and rac-methadone, respectively). Only 1 subject had duplication of functional CYP2D6 alleles and the oral clearance of the three analytes was not markedly altered. Conclusions: CYP2D6 poor, intermediate and extensive metabolizer genotypes did not appear to impact on the oral clearance of (R)-, (S)- or rac-methadone. In addition, methadone dosage requirements were not influenced by CYP2D6 genotypes in these subjects. However, the impact of duplication of functional CYP2D6 alleles on oral clearance and dosage requirements requires further investigation. |
Keywords: | Humans Pain Opioid-Related Disorders Methadone Cytochrome P-450 CYP2D6 Analgesics, Opioid Pregnancy Genotype Phenotype Alleles Stereoisomerism Adult Female Male |
DOI: | 10.5414/CPP45410 |
Published version: | http://www.clinnephrol.com/index.php?id=93&issueId=221&PHPSESSID=dfae7d08008d5cbb7b9d03c685c7254b |
Appears in Collections: | Aurora harvest 6 Pharmacology publications |
Files in This Item:
There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.