Park P-W, Seo Y H, Ahn J Y, Kim K-A, Park J-Y
Department of Laboratory Medicine, Gil Hospital, Gachon University, Incheon, Korea.
J Clin Pharm Ther. 2009 Oct;34(5):569-74. doi: 10.1111/j.1365-2710.2009.01057.x.
Carbamazepine (CBZ) is metabolized mainly by the CYP3A family of enzymes, which includes CYP3A4 and CYP3A5. Several studies have suggested that the CYP3A53 genotype influences the pharmacokinetics of CYP3A substrates. The present study aimed to assess the effect of the CYP3A53 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 CYP3A51/3) and 21 patients were CYP3A5 non-expressors (CYP3A53/*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.
卡马西平（CBZ）主要由细胞色素P450 3A（CYP3A）酶家族代谢，该家族包括CYP3A4和CYP3A5。多项研究表明，CYP3A53基因型会影响CYP3A底物的药代动力学。本研究旨在评估CYP3A53基因型对韩国癫痫患者稳态时CBZ血清浓度的影响。
测定了35例韩国癫痫患者的CBZ血清浓度，并确定了他们的CYP3A5基因型。14例患者为CYP3A5表达者（2例为CYP3A5*1/1，12例为CYP3A51/3），21例患者为CYP3A5非表达者（CYP3A53/*3）。CYP3A5表达者的CBZ剂量标准化浓度（均值±标准差）为9.9±3.4 ng/mL/mg，CYP3A5非表达者为13.1±4.5 ng/mL/mg（P = 0.032）。CYP3A5非表达者的CBZ口服清除率显著高于CYP3A5表达者（0.056±0.017 L/h/kg对0.040±0.014 L/h/kg，P = 0.004）。CYP3A5基因型影响韩国癫痫患者的CBZ浓度，是导致癫痫患者CBZ处置个体差异的一个因素。
