Effect of high-fat meal and ABCB1 C3435 T polymorphism on pharmacokinetics of nifedipine in healthy Chinese subjects / 中国药理学通报

ABSTRACT

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 groupsfasting 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 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<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.