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| Item Type: | Article |
|---|---|
| Title: | Genetic variation at the CYP2C locus and its association with torsemide biotransformation |
| Creators Name: | Vormfelde, S.V., Schirmer, M., Toliat, M.R., Meineke, I., Kirchheiner, J., Nuernberg, P. and Brockmoeller, J. |
| Abstract: | In 97 unselected volunteers and two additional homozygous carriers of CYP2C9(*)3, we investigated the oral clearance of torsemide in relation to 37 polymorphisms at the CYP2C gene locus. Torsemide total oral clearance was linearly associated with the number of CYP2C9(*)3 alleles (geometric mean: 59, 40 and 20 ml/min in carriers of no, one and two alleles) and so were the methyl- and ring-hydroxylation but not the carboxylation clearance. Haplotypes including the CYP2C9(*)3 allele were similarly associated with the clearances but no other variant and no haplotype not including the CYP2C9(*)3 variant. The extended haplotype length (EHL) of the CYP2C9 haplotypes was positively associated with higher activity of the gene product. Torsemide total oral clearance was predictable with r(2)=82.1% using plasma concentrations at 0.5, 1, 2 and 24 h. In conclusion, torsemide's biotransformation strongly depended on the CYP2C9(*)3 variant but no other. Higher clearance CYP2C9 haplotypes appear to be evolutionarily selected. |
| Keywords: | CYP2C9, Evolutionary selection, Haplotype, Hepatic clearance, Polymorphism, Torsemide |
| Source: | Pharmacogenomics Journal |
| ISSN: | 1470-269X |
| Publisher: | Nature Publishing Group |
| Volume: | 7 |
| Page Range: | 200-211 |
| Date: | 1 June 2007 |
| Official Publication: | https://doi.org/10.1038/sj.tpj.6500410 |
| PubMed: | View item in PubMed |
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