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Effect of CYP3A5*3 genotype on serum carbamazepine concentrations at steady‐state in Korean epileptic patients
Author(s) -
Park P.W.,
Seo Y. H.,
Ahn J. Y.,
Kim K.A.,
Park J.Y.
Publication year - 2009
Publication title -
journal of clinical pharmacy and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.622
H-Index - 73
eISSN - 1365-2710
pISSN - 0269-4727
DOI - 10.1111/j.1365-2710.2009.01057.x
Subject(s) - carbamazepine , cyp3a , cyp3a5 , pharmacokinetics , pharmacology , genotype , pharmacogenetics , anticonvulsant , medicine , chemistry , epilepsy , metabolism , cytochrome p450 , psychiatry , biochemistry , gene
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.