Kim Su Cheol, Kim Myeong Gyu
Int J Clin Pharmacol Ther. 2019 Mar;57(3):144-151. doi: 10.5414/CP203357.
Genetic polymorphisms in might contribute to interindividual variability in the pharmacokinetics of valproic acid (VPA). However, whether the 541A>G and 552A>C variants decrease VPA concentration remains controversial. Herein, we performed a meta-analysis to evaluate the influence of genetic polymorphisms on VPA pharmacokinetics.
Searches, two-step selection, data extraction, and quality assessment were performed using a conventional protocol, and the influence of genetic polymorphisms on concentration-to-dose ratio was quantitatively assessed by pooled analysis using the Comprehensive Meta-Analysis program.
Six studies using monotherapy were included in the quantitative analysis. Concentration-to-dose ratio of 541A>G and 552A>C homozygous variant were significantly lower than that of the wild-type (WT; standardized difference in means (SDM) = -0.771, 95% confidence interval (CI) = -1.123 to -0.419; SDM = -0.879, 95% CI = -1.257 to -0.500, respectively). Differences were also significant in both child and adult subgroups analysis. For heterozygous variants, there was no significant difference in concentration-to-dose ratio between 541A>G and 552A>C heterozygous variant and WT (SDM = -0.183, 95% CI = -0.449 to 0.084; SDM = -0.275, 95% CI = -0.647 to 0.097, respectively).
CONCLUSION: In conclusion, concentration-to-dose ratio for VPA monotherapy were significantly lower for homozygous variants 541A>G and 552A>C than for the WT. .
[基因名称]的基因多态性可能导致丙戊酸（VPA）药代动力学存在个体间差异。然而，541A>G和552A>C变体是否会降低VPA浓度仍存在争议。在此，我们进行了一项荟萃分析，以评估[基因名称]基因多态性对VPA药代动力学的影响。
采用常规方案进行检索、两步筛选、数据提取和质量评估，并使用综合荟萃分析程序通过汇总分析定量评估[基因名称]基因多态性对浓度-剂量比的影响。
定量分析纳入了6项使用单一疗法的研究。541A>G和552A>C纯合变体的浓度-剂量比显著低于野生型（WT；平均标准化差异（SDM）=-0.771，95%置信区间（CI）=-1.123至-0.419；SDM=-0.879，95%CI=-1.257至-0.500）。在儿童和成人亚组分析中差异也很显著。对于杂合变体，541A>G和552A>C杂合变体与WT之间的浓度-剂量比无显著差异（SDM=-0.183，95%CI=-0.449至0.084；SDM=-0.275，95%CI=-0.647至0.097）。
总之，VPA单一疗法中，541A>G和552A>C纯合变体的浓度-剂量比显著低于野生型。
