Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/42004
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dc.contributor.author | Coller, J. | - |
dc.contributor.author | Joergensen, C. | - |
dc.contributor.author | Foster, D. | - |
dc.contributor.author | James, H. | - |
dc.contributor.author | Gillis, D. | - |
dc.contributor.author | Christrup, L. | - |
dc.contributor.author | Somogyi, A. | - |
dc.date.issued | 2007 | - |
dc.identifier.citation | International Journal of Clinical Pharmacology and Therapeutics, 2007; 45(7):410-417 | - |
dc.identifier.issn | 0946-1965 | - |
dc.identifier.uri | http://hdl.handle.net/2440/42004 | - |
dc.description.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. | - |
dc.description.statementofresponsibility | J.K. Coller, C. Joergensen, D.J.R. Foster, H. James, D. Gillis, L. Christrup and A.A. Somogyi | - |
dc.language.iso | en | - |
dc.publisher | Dustri-Verlag Dr Karl Feistle | - |
dc.source.uri | http://www.clinnephrol.com/index.php?id=93&issueId=221&PHPSESSID=dfae7d08008d5cbb7b9d03c685c7254b | - |
dc.subject | Humans | - |
dc.subject | Pain | - |
dc.subject | Opioid-Related Disorders | - |
dc.subject | Methadone | - |
dc.subject | Cytochrome P-450 CYP2D6 | - |
dc.subject | Analgesics, Opioid | - |
dc.subject | Pregnancy | - |
dc.subject | Genotype | - |
dc.subject | Phenotype | - |
dc.subject | Alleles | - |
dc.subject | Stereoisomerism | - |
dc.subject | Adult | - |
dc.subject | Female | - |
dc.subject | Male | - |
dc.title | Lack of influence of CYP2D6 genotype on the clearance of (R)- (S)- and racemic-methadon | - |
dc.type | Journal article | - |
dc.identifier.doi | 10.5414/CPP45410 | - |
pubs.publication-status | Published | - |
dc.identifier.orcid | Coller, J. [0000-0002-8273-5048] | - |
dc.identifier.orcid | Foster, D. [0000-0002-7345-4084] | - |
dc.identifier.orcid | Somogyi, A. [0000-0003-4779-0380] | - |
Appears in Collections: | Aurora harvest 6 Pharmacology publications |
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