Rodriguez Antona, CristinaNiemi, MBackman, J TKajosaari, L INeuvonen, P JRobledo Batanero, MercedesIngelman-Sundberg, M2024-02-062024-02-062008-08Pharmacogenomics J. 2008;8(4):268-77.http://hdl.handle.net/20.500.12105/17495Cytochrome 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.engAMhttp://creativecommons.org/licenses/by-nc-nd/4.0/Aryl Hydrocarbon HydroxylasesCarbamatesCytochrome P-450 CYP2C8Genetic VariationHaplotypesHumansPaclitaxelPiperidinesWhite PeopleAttribution-NonCommercial-NoDerivatives 4.0 Internacional179238518426810.1038/sj.tpj.65004821473-1150The pharmacogenomics journalopen access