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Browsing by discipline "Clinical Pharmacology"

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  • Frequencies of CYP2B6 variants in a Finnish population 
    Fredman, Johannes (2015)
    Cytochrome P-450 2B6 (CYP2B6) is a monoxygenase enzyme contributing to the metabolism of drugs and xenobiotics. Significant genetic variability in CYP2B6 exists in different ethnic groups, contributing to interindividual differences in pharmacokinetics and drug response. The aim of this study was to investigate the frequencies of CYP2B6 single nucleotide variations (SNVs) in the Finnish population. The frequencies of nine CYP2B6 SNVs were determined in 261 healthy Finnish volunteers by allelic discrimination with TaqMan 5'-nuclease assays. The variant allele frequencies of CYP2B6 c.419G>A (p.Arg140Gln), c.516G>T (p.Gln172His), c.785A>G (p.Lys262Arg), c.1172T>A (p.Ile391Asn), and c.1459C>T (p.Arg487Cys) were 0.58% (95% confidence interval 0.20-1.7%), 19.3% (16.1-22.9%), 23.8% (20.3-27.6%), 0.4% (0.11-1.39%), and 13.2% (10.6-16.4%), respectively. None of the subjects carried the CYP2B6 c.136A>G (p.Met46Val), c.296G>A (p.Gly99Glu), c.415A>G (p.Lys139Glu), or c.983T>C (p.Ile328Thr) SNVs. The variant alleles of CYP2B6 occur in Finnish population in similar or slightly lower frequencies as described in previous studies with other European Caucasian subjects.
  • Single nucleotide polymorphisms of ABCC2, ABCG2, SLCO1B1 and SLCO1B3 genes and methotrexate pharmacokinetics in children with ALL 
    Zetterman, Teemu (2013)
    Methotrexate is an antifolate drug used in the Nordic Society of Pediatric Haematology and Oncology (NOPHO) treatment protocol for childhood acute lymphoblastic leukemia (ALL). Methotrexate is a substrate of several transporter proteins, but the exact extent to which these proteins affect methotrexate pharmacokinetics is still unclear. In this retrospective study, the effects of ABCC2, SLCO1B1, SLCO1B3 and ABCG2 genetic variants as well as clinical covariates on methotrexate pharmacokinetics were studied in a population of 90 Finnish children with ALL, treated in 1992 – 2001 according to the NOPHO treatment protocol for ALL. None of the investigated genetic variants had a significant effect on the pharmacokinetic parameters of methotrexate. These data indicate that these transporter variants play only a minor, if any, role in explaining interindividual variability in methotrexate pharmacokinetics in the treatment of Finnish children with ALL according to the NOPHO protocol.

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