Impact of 14 types of genetic polymorphisms on antihypertensive efficacy of felodipine in healthy Chinese subjects

摘要

Objective: This study evaluated different influences of 14 single nucleotide polymorphisms (SNPs) and demographic factors leading to individual differences in the antihypertensive efficacy of felodipine in healthy Chinese subjects. Materials and methods: 24 subjects were sequenced for candidate SNPs. Plasma samples were obtained as clinical trial protocol, and were determined by a HPLC-MS/MS method. Pharmacokinetic parameters were calculated by WinNonlin 6.0. Statistical analysis was mainly performed by SPSS 22.0. A multiple linear regression model provided different weight coefficients of different demographic and genetic factors. Results: The trend of C-max, is almost consistent with AUC(ss) increase, but t(max), of individuals is different; the antihypertensive effect of felodipine is individually different. A significant association was observed between systolic blood pressure decrease (ASBP) and SNPs of CACNA1C, CACNA1D, GNB3 respectively. while CACNA1C and CACNA1D were associated with diastolic blood pressure decrease (Delta DBP). CYP3A5 rs766746 and CYP3A4 rs2242480 were linked with C-max and AUC(ss), and ABCB1 rs1045642 was associated with T-1/2. Significant relationships were shown between AUC(ss) and Delta SBP (p = 0.022) as well as C-max and ASBP (p = 0.015). Conclusion: The efficacy of felodipine is individually different, influenced especially by CACNA1C rs1051375 and ABCB1 rs1045642. Delta DBP is associated with Delta SBP in multiple-dosing of felodipine in healthy Chinese subjects.