Zubiaur Pablo, Saiz-Rodríguez Miriam, Koller Dora, Ovejero-Benito María Carmen, Wojnicz Aneta, Abad-Santos Francisco
Clinical Pharmacology Department, Hospital Universitario de la Princesa, Instituto Teófilo Hernando, Universidad Autónoma de Madrid (UAM), Instituto de Investigación Sanitaria la Princesa (IP), Madrid, Spain.
UICEC Hospital Universitario de la Princesa, Plataforma SCReN (Spanish Clinical Reseach Network), Instituto de Investigación Sanitaria la Princesa (IP), Madrid, Spain.
Pharmacogenomics. 2018 Nov;19(16):1285-1297. doi: 10.2217/pgs-2018-0101. Epub 2018 Oct 18.
Several polymorphisms have been identified in ABCB1, the gene encoding for the P-glycoprotein. This transporter alters the pharmacokinetics or effectiveness of drugs by excreting them from cells where it is expressed (e.g., blood-brain barrier, intestine or tumors). No consensus has been reached regarding the functional consequences of these polymorphisms in the transporter's function. The aim of this review was to describe a methodology that allows the assessment of P-gp function when harboring polymorphisms. We describe how to obtain cell lines with high expression levels of the transporter with polymorphisms and several tactics to measure its expression and activity. This methodology may help elucidate the contribution of polymorphisms in ABCB1 to drug pharmacokinetics, effectiveness and safety or to cancer chemotherapy failure.
在编码P-糖蛋白的基因ABCB1中已鉴定出几种多态性。这种转运蛋白通过将药物从其表达的细胞（如血脑屏障、肠道或肿瘤细胞）中排出，从而改变药物的药代动力学或药效。关于这些多态性对转运蛋白功能的影响，尚未达成共识。本综述的目的是描述一种方法，该方法可用于评估携带多态性时P-糖蛋白的功能。我们描述了如何获得具有多态性的高表达转运蛋白的细胞系，以及几种测量其表达和活性的策略。该方法可能有助于阐明ABCB1中的多态性对药物药代动力学、药效和安全性或癌症化疗失败的影响。
