Marwa Karol J, Kapesa Anthony, Kamugisha Erasmus, Swedberg Göte
Department of Pharmacology, Catholic University of Health and Allied Sciences, Mwanza, Tanzania.
Department of Community Medicine, Catholic University of Health and Allied Sciences, Mwanza, Tanzania.
Pharmgenomics Pers Med. 2023 May 18;16:449-461. doi: 10.2147/PGPM.S379945. eCollection 2023.
Sub-Saharan Africa (SSA) population is genetically diverse and heterogenous thus variability in drug response among individuals is predicted to be high. Cytochrome P450 (CYP450) polymorphisms is a major source of variability in drug response. This systematic review presents the influence of CYP450 single nucleotide polymorphisms (SNPs), particularly CYP3A41B, CYP2B66 and CYP3A5*3 on antimalarial drug plasma concentrations, efficacy and safety in SSA populations.
Searching for relevant studies was done through Google Scholar, Cochrane Central Register of controlled trials (CENTRAL), PubMed, Medline, LILACS, and EMBASE online data bases. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were used. Two independent reviewers extracted data from the studies.
Thirteen studies reporting the influence of CYP450 SNPs on plasma concentrations, efficacy and safety were included in the final data synthesis. CYP3A41B, CYP3A55, CYP2B66 and CYP2C82 did not affect antimalarial drug plasma concentration significantly. There was no difference in treatment outcomes between malaria patients with variant alleles and those with wild type alleles.
This review reports lack of influence of CYP3A41B, CYP3A53, CYP2C83 and CYP2B66 SNPs on PK profiles, efficacy and safety in SSA among malaria patients.
撒哈拉以南非洲（SSA）地区人群在基因上具有多样性和异质性，因此预计个体间药物反应的变异性较高。细胞色素P450（CYP450）基因多态性是药物反应变异性的主要来源。本系统评价阐述了CYP450单核苷酸多态性（SNP），特别是CYP3A41B、CYP2B66和CYP3A5*3对SSA地区人群抗疟药物血浆浓度、疗效及安全性的影响。
通过谷歌学术、Cochrane对照试验中心注册库（CENTRAL）、PubMed、Medline、拉丁美洲及加勒比地区卫生科学数据库（LILACS）和EMBASE在线数据库检索相关研究。采用系统评价和Meta分析的首选报告项目（PRISMA）指南。两名独立的评价者从研究中提取数据。
最终的数据综合纳入了13项报告CYP450 SNP对血浆浓度、疗效和安全性影响的研究。CYP3A41B、CYP3A55、CYP2B66和CYP2C82对抗疟药物血浆浓度无显著影响。携带变异等位基因的疟疾患者与携带野生型等位基因的患者在治疗结局上无差异。
本评价报告了在SSA地区疟疾患者中，CYP3A41B、CYP3A53、CYP2C83和CYP2B66 SNP对药代动力学特征、疗效及安全性缺乏影响。
