Novartis NKK, Tokyo, Japan.
PharmaGenesis London, London, UK.
Clin Transl Sci. 2020 Sep;13(5):848-860. doi: 10.1111/cts.12769. Epub 2020 Mar 31.
Polymorphisms in drug transporters, like the adenosine triposphate-binding cassette (ABC) and solute carrier (SLC) superfamilies, may contribute to the observed diversity in drug response in African patients. This review aims to provide a comprehensive summary and analysis of the frequencies and distributions in African populations of ABC and SLC variants that affect drug pharmacokinetics (PK) and pharmacodynamics (PD). Of polymorphisms evaluated in African populations, SLCO1B1 rs4149056 and SLC22A6 rs1158626 were found at markedly higher frequencies than in non-African populations. SLCO1B1 rs4149056 was associated with reduction in rifampin exposure, which has implications for dosing this important anti-tuberculosis therapy. SLC22A6 rs1158626 was associated with increased affinity for antiretroviral drugs. Genetic diversity in SLC and ABC transporters in African populations has implications for conventional therapies, notably in tuberculosis and HIV. More PK and PD data in African populations are needed to assess potential for a different response to drugs compared with other global populations.
药物转运体（如三磷酸腺苷结合盒（ABC）和溶质载体（SLC）超家族）的多态性可能导致非洲患者对药物反应的观察到的多样性。本综述旨在全面总结和分析影响药物药代动力学（PK）和药效学（PD）的 ABC 和 SLC 变体在非洲人群中的频率和分布。在非洲人群中评估的多态性中，SLCO1B1 rs4149056 和 SLC22A6 rs1158626 的频率明显高于非非洲人群。SLCO1B1 rs4149056 与利福平暴露减少有关，这对这种重要的抗结核治疗的剂量有影响。SLC22A6 rs1158626 与抗逆转录病毒药物的亲和力增加有关。SLC 和 ABC 转运体在非洲人群中的遗传多样性对常规治疗有影响，特别是在结核病和 HIV 方面。需要在非洲人群中获得更多的 PK 和 PD 数据，以评估与其他全球人群相比对药物的潜在不同反应。
