2026-05-22T05:27:44Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/174952024-11-29T17:23:44Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
Rodriguez Antona, Cristina
author
Niemi, M
author
Backman, J T
author
Kajosaari, L I
author
Neuvonen, P J
author
Robledo Batanero, Mercedes
author
Ingelman-Sundberg, M
funder
The Swedish Research Council
funder
The Swedish Cancer Foundation
funder
Sigrid Juselius Foundation (Helsinki, Finland).
funder
European Community
funder
Marie Curie
2024-02-06T09:07:34Z
2024-02-06T09:07:34Z
2008-08
Pharmacogenomics J. 2008;8(4):268-77.
10.1038/sj.tpj.6500482
1473-1150
The pharmacogenomics journal
17923851
http://hdl.handle.net/20.500.12105/17495
Cytochrome P450 2C8 (CYP2C8) plays a major role in the metabolism of therapeutically important drugs which exhibit large interindividual differences in their pharmacokinetics. In order to evaluate any genetic influence on this variation, a CYP2C8 phenotype-genotype evaluation was carried out in Caucasians. Two novel CYP2C8 haplotypes, named B and C with frequencies of 24 and 22% in Caucasians, respectively, were identified and caused a significantly increased and reduced paclitaxel 6alpha-hydroxylation, respectively, as evident from analyses of 49 human liver samples. In healthy white subjects, CYP2C8*3 and the two novel haplotypes significantly influenced repaglinide pharmacokinetics in SLCO1B1c.521T/C heterozygous individuals: haplotype B was associated with reduced and haplotype C with increased repaglinide AUC (0-infinity). Functional studies suggested -271C>A (CYP2C8*1B) as a causative SNP in haplotype B. In conclusion, two novel common CYP2C8 haplotypes were identified and significantly associated with altered rate of CYP2C8-dependent drug metabolism in vitro and in vivo.
eng
Characterization of novel CYP2C8 haplotypes and their contribution to paclitaxel and repaglinide metabolism.
journal article
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