Pharmacogenetics of opioid medications for relief of labor pain and post-cesarean pain: a systematic review and meta-analysis.

IF 2.4 3区医学 Q3 PHARMACOLOGY & PHARMACY European Journal of Clinical Pharmacology Pub Date : 2025-01-07 DOI:10.1007/s00228-024-03798-z

Martina Giacon, Sarah Cargnin, Maria Talmon, Salvatore Terrazzino

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Abstract

Objective: Several studies have attempted to identify genetic determinants of clinical response to opioids administered during labor or after cesarean section. However, their results were often contrasting. A systematic review and meta-analysis was conducted to quantitatively assess the association between gene polymorphisms and clinical outcomes of opioid administration in the treatment of labor pain and post-cesarean pain.

Methods: A comprehensive search was performed up to December 2023 using PubMed, Web of Knowledge, Cochrane Library, and OpenGrey databases. The clinical endpoints of interest were pain score after opioid treatment, total opioid consumption, patient's analgesic satisfaction, and incidence of opioid side effects. Random-effects meta-analyses were conducted when data were available in at least three studies.

Results: Twenty-six studies enrolling 7765 patients were included in the systematic review. Overall, a total of 12 candidate polymorphic genes (OPRM1, COMT, CYP2D6, CYP3A4, ABCB1, ABCC3, UGT2B7, CGRP, OPRK1, OPRD1, KCNJ6, KCNJ9) were considered by the included studies, among which the most investigated variant was OPRM1 rs1799971. Overall pooled results indicated that individuals carrying the G allele of OPRM1 rs1799971 required higher opioid doses for pain management in comparison to rs1799971 AA subjects (standardized mean difference: 0.26; 95% CI: 0.09-0.44; P = 0.003). Such an association was confirmed in the subgroups of patients with labor pain and post-cesarean pain.

Conclusion: The present meta-analysis provides strong evidence of an association between OPRM1 rs1799971 and opioid dose requirement for relief of labor pain or post-cesarean pain. However, given the insufficient evidence for other polymorphic gene variants, large studies are still needed to investigate the impact of genetic variability on the efficacy and safety of opioid medications for relief of labor pain and post-cesarean pain (INPLASY Registration No. 202410040).

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缓解分娩疼痛和剖宫产后疼痛的阿片类药物的药物遗传学：系统回顾和荟萃分析。

目的：几项研究试图确定在分娩期间或剖宫产后给予阿片类药物的临床反应的遗传决定因素。然而，他们的结果往往是截然相反的。通过系统回顾和荟萃分析，定量评估基因多态性与阿片类药物治疗分娩疼痛和剖宫产后疼痛的临床结果之间的关系。方法：综合检索PubMed、Web of Knowledge、Cochrane Library和OpenGrey数据库，检索截止到2023年12月。临床终点为阿片类药物治疗后疼痛评分、阿片类药物总消耗量、患者镇痛满意度和阿片类药物副作用发生率。当至少有三项研究的数据可用时，进行随机效应荟萃分析。结果：26项研究纳入了7765例患者。总体而言，纳入的研究共考虑了12个候选多态性基因（OPRM1、COMT、CYP2D6、CYP3A4、ABCB1、ABCC3、UGT2B7、CGRP、OPRK1、OPRD1、KCNJ6、KCNJ9），其中研究最多的变异是OPRM1 rs1799971。总体汇总结果表明，携带OPRM1 rs1799971 G等位基因的个体与rs1799971 AA受试者相比，需要更高的阿片类药物剂量来控制疼痛(标准化平均差异：0.26；95% ci: 0.09-0.44；p = 0.003)。这种关联在分娩疼痛和剖宫产后疼痛患者亚组中得到证实。结论：本meta分析提供了强有力的证据，证明OPRM1 rs1799971与缓解分娩疼痛或剖宫产后疼痛的阿片类药物剂量需求有关。然而，由于其他多态性基因变异的证据不足，仍然需要大量的研究来调查遗传变异对阿片类药物缓解分娩疼痛和剖宫产后疼痛的有效性和安全性的影响（INPLASY注册号202410040）。

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来源期刊

European Journal of Clinical Pharmacology 医学-药学

CiteScore

5.40

自引率

3.40%

发文量

170

审稿时长

3-8 weeks

期刊介绍： The European Journal of Clinical Pharmacology publishes original papers on all aspects of clinical pharmacology and drug therapy in humans. Manuscripts are welcomed on the following topics: therapeutic trials, pharmacokinetics/pharmacodynamics, pharmacogenetics, drug metabolism, adverse drug reactions, drug interactions, all aspects of drug development, development relating to teaching in clinical pharmacology, pharmacoepidemiology, and matters relating to the rational prescribing and safe use of drugs. Methodological contributions relevant to these topics are also welcomed. Data from animal experiments are accepted only in the context of original data in man reported in the same paper. EJCP will only consider manuscripts describing the frequency of allelic variants in different populations if this information is linked to functional data or new interesting variants. Highly relevant differences in frequency with a major impact in drug therapy for the respective population may be submitted as a letter to the editor. Straightforward phase I pharmacokinetic or pharmacodynamic studies as parts of new drug development will only be considered for publication if the paper involves -a compound that is interesting and new in some basic or fundamental way, or -methods that are original in some basic sense, or -a highly unexpected outcome, or -conclusions that are scientifically novel in some basic or fundamental sense.