高脂饮食及ABCB1基因多态性对硝苯地平在健康受试者体内药动学的影响

Effect of high-fat meal and ABCB1 C3435T polymorphism on pharmacokinetics of nifedipine in healthy Chinese subjects

目的探讨高脂饮食及ABCB1 C3435T基因多态性对硝苯地平人体药动学的影响。方法 90名汉族健康受试者分为空腹组和高脂餐组,各45名。分别在单次服用90 mg硝苯地平缓释片后,定时采血,用高效液相色谱-质谱联用法分析受试者硝苯地平血药浓度,采用PCR-限制性片段长度多态性分析法检测ABCB1 C3435T基因型。结果空腹组中,C/C、C/T、T/T 3种基因型分别为13例、24例、8例;T/T基因型受试者比C/C基因型受试者平均药时曲线下面积AUC0-∞增加了46.34%,分别为3252.08和2222.24(单位:μg·h·L-1),但差异无显著性(P=0.066)。空腹组与高脂餐组健康受试者的药动学参数Tpeak、Cmax、AUC0-48差异有显著性(P<0.05)。结论高脂饮食导致硝苯地平的吸收加快,吸收量增加;ABCB1基因型对硝苯地平体内药动学无明显影响。

Aim To determine the effects of high-fat meal and ABCB1 C3435 T polymorphism on the phar-macokinetics of nifedipine in the healthy Chinese sub-jects. Methods A total of 90 unrelated healthy Han subjects were divided into two groups：fasting group （ n=45 ） and high-fat meal group （ n=45 ） and then they received a single oral dose of 90 mg extended release tablet. Multiple blood samples were collected after 48 h, and the plasma concentrations of nifedipine were determined by high performance liquid chromatogra-phy- mass spectrometry （ LC-MS ） . PCR-restriction fragment length polymorphism （ RFLP ） analysis was performed to detect the C3435 T polymorphism in AB-CB1 gene. Results The numbers of individuals carry-ing C/C, C/T and T/T genotypes in fasting group were＆amp;nbsp;13, 24 and 8, respectively. The mean area under the curve （ AUC0-∞） in subjects carrying T/T genotype distinctly increased by 46. 34% compared with subjects with C/C genotype, but there was no statistically sig-nificant difference （P=0. 066）. In addition, pharma-cokinetic parameters including Tpeak, Cmax and AUC0-48 had statistically significant differences between fasting group and high-fat meal group （ all P＆lt;0. 05 ） . Con-clution High-fat meal can speed the absorption and increase the extent of nifedipine absorption; ABCB1 C3435 T polymorphism almost does not affect the phar-macokinetics of nifedipine.