2026-08-29T14:08:04Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/174952024-11-29T17:23:44Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc 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 author 2008-08 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. 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 Characterization of novel CYP2C8 haplotypes and their contribution to paclitaxel and repaglinide metabolism.