Effect of CYP3A5*3 genotype on serum carbamazepine concentrations at steady-state in Korean epileptic patients

P. W. Park, Y. H. Seo, J. Y. Ahn, K. A. Kim, J. Y. Park

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    52 Citations (Scopus)

    Abstract

    Background and Objective: Carbamazepine (CBZ) is metabolized mainly by the CYP3A family of enzymes, which includes CYP3A4 and CYP3A5. Several studies have suggested that the CYP3A5*3 genotype influences the pharmacokinetics of CYP3A substrates. The present study aimed to assess the effect of the CYP3A5*3 genotype on serum concentration of CBZ at the steady-state in Korean epileptic patients. Method: The serum concentrations of CBZ in 35 Korean epileptic patients were measured and their CYP3A5 genotype was determined. Fourteen patients were CYP3A5 expressors (two for CYP3A5*1/*1 and 12 for CYP3A5*1/*3) and 21 patients were CYP3A5 non-expressors (CYP3A5*3/*3). Dose-normalized concentrations (mean ± SD) of CBZ were 9·9 ± 3·4 ng/mL/mg for CYP3A5 expressors and 13·1 ± 4·5 ng/mL/mg for CYP3A5 non-expressors (P = 0·032). The oral clearance of CBZ was significantly higher in CYP3A5 non-expressors than that of CYP3A5 expressors (0·056 ±0·017 L/h/kg vs. 0·040 ± 0·014 L/h/kg, P = 0·004). The CYP3A5 genotype affected the CBZ concentrations in Korean epileptic patients and is a factor that may contribute to inter-individual variability in CBZ disposition in epileptic patients.

    Original languageEnglish
    Pages (from-to)569-574
    Number of pages6
    JournalJournal of Clinical Pharmacy and Therapeutics
    Volume34
    Issue number5
    DOIs
    Publication statusPublished - 2009 Oct

    Keywords

    • CYP3A53
    • Carbamazepine
    • Cytochrome P450 3A5 (CYP3A5)
    • Pharmacogenetics
    • Therapeutic drug monitoring

    ASJC Scopus subject areas

    • Pharmacology
    • Pharmacology (medical)

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