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

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 center dot 9 +/- 3 center dot 4 ng/mL/mg for CYP3A5 expressors and 13 center dot 1 +/- 4 center dot 5 ng/mL/mg for CYP3A5 non-expressors (P = 0 center dot 032). The oral clearance of CBZ was significantly higher in CYP3A5 non-expressors than that of CYP3A5 expressors (0 center dot 056 +/- 0 center dot 017 L/h/kg vs. 0 center dot 040 +/- 0 center dot 014 L/h/kg, P = 0 center dot 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.