Effect ofCYP3A5*3genotype on serum carbamazepine concentrations at steady-state in Korean epileptic patients

Abstract

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. 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.