The effect of CYP3A4 genetic polymorphisms on the pharmacokinetics of calcineurin inhibitors in renal transplant recipients: a systematic review and meta-analysis protocol

BackgroundCalcineurin inhibitors (CNIs) are metabolized by CYP3A4. Polymorphisms in the CYP3A4 gene alter the activity of CYP3A4 protein and therefore affect the CNIs concentrations. Results of studies that investigated the association between CYP3A4 polymorphisms and CNIs pharmacokinetics are controversial. Therefore, this systematic review and meta-analysis will evaluate the effect of CYP3A4 polymorphisms on the pharmacokinetics of CNIs in renal transplant recipients. MethodThis protocol is developed according to the PRISMA-P guideline and registered in PROSPERO (CRD42020145219). The MeSH/Emtree terms of CYP3A4 polymorphisms and CNIs pharmacokinetics in PECO-based question will be obtained from the comprehensive literature search on PubMed/MEDLINE, Scopus, Web of Science, Embase, CENTRAL, and ProQuest without any language limitation from 1 January 1998 to 31 March 2021. Google Scholar search engine, registries, conference papers, and key journals will also be searched. Screening, selection, quality assessment, and data extraction will be performed by two independent reviewers. Statistical heterogeneity will be calculated by the Q Cochrane test and I2 statistic. Publication bias and sensitivity analysis will be evaluated by appropriate tests. Results and conclusionAccording to the meta-analysis of the aggregated data from the relevant primary studies, the association between CYP3A4 polymorphisms and CNIs pharmacokinetics will be reported, which possibly help the pharmacogenetic-guided dosing approach.