Effect of high-fat meal and ABCB1 C3435 T polymorphism on pharmacokinetics of nifedipine in healthy Chinese subjects
10.3969/j.issn.1001-1978.2014.04.027
- VernacularTitle: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
- Author:
Jiangfeng LI
;
Liang YAN
;
Xiaofei WANG
;
Xiaotian LI
;
Shengjun ZHANG
;
Lirong ZHANG
- Publication Type:Journal Article
- Keywords:
ABCB1;
nifedipine;
pharmacokinetics;
gene polymorphism;
high-fat meal;
LC/MS/MS
- From:
Chinese Pharmacological Bulletin
2014;(4):566-569
- CountryChina
- Language:Chinese
-
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 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 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.
