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

Abstract

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 (ΔSBP) and SNPs of CACNA1C, CACNA1D, GNB3 respectively, while CACNA1C and CACNA1 were associated with diastolic blood pressure decrease (ΔDBP). 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 ΔSBP (p = 0.022) as well as C_max and ΔSBP (p = 0.015).

Conclusion: The efficacy of felodipine is individually different, influenced especially by CACNA1C rs1051375 and ABCB1 rs1045642. ΔDBP is associated with ΔSBP in multiple-dosing of felodipine in healthy Chinese subjects.