Abstract
Adverse drug reactions (ADRs) are one of the major causes of morbidity and mortality worldwide. It is well-known that individual genetic make-up is one of the causative factors of ADRs. Approximately 14 million single nucleotide polymorphisms (SNPs) are distributed throughout the entire human genome and every patient has a distinct genetic make-up which influences their response to drug therapy. Cytochrome P450 2B6 (CYP2B6) is involved in the metabolism of antiretroviral, antimalarial, anticancer, and antidepressant drugs. These drug classes are commonly in use worldwide and face specific population variability in side effects and dosing. Parts of this variability may be caused by single nucleotide polymorphisms (SNPs) in the CYP2B6 gene that are associated with altered protein expression and catalytic function. Population variability in the CYP2B6 gene leads to changes in drug metabolism which may result in adverse drug reactions or therapeutic failure. So far more than 30 non-synonymous variants in CYP2B6 gene have been reported. The occurrence of these variants show intra and interpopulation variability, thus affecting drug efficacy at individual and population level. Differences in disease conditions and affordability of drug therapy further explain why some individuals or populations are more exposed to CYP2B6 pharmacogenomics associated ADRs than others. Variabilities in drug efficacy associated with the pharmacogenomics of CYP2B6 have been reported in various populations. The aim of this review is to highlight reports from various ethnicities that emphasize on the relationship between CYP2B6 pharmacogenomics variability and the occurrence of adverse drug reactions. In vitro and in vivo studies evaluating the catalytic activity of CYP2B6 variants using various substrates will also be discussed. While implementation of pharmacogenomic testing for personalized drug therapy has made big progress, less data on pharmacogenetics of drug safety has been gained in terms of CYP2B6 substrates. Therefore, reviewing the existing evidence on population variability in CYP2B6 and ADR risk profiles suggests that, in addition to other factors, the knowledge on pharmacogenomics of CYP2B6 in patient treatment may be useful for the development of personalized medicine with regards to genotype-based prescription.
Highlights
Adverse drug reactions (ADRs) are globally one of the major causes of morbidity and mortality (Giardina et al, 2018; Patel and Patel, 2018)
Genetic polymorphisms in drug transporters, drug targets and most importantly drug metabolizing enzymes have been emphasized over the years as one of the major factors causing variability in drug response (Weinshilboum, 2003; Evans and Relling, 2004)
The scope of this review is to report the evidence on ADRs of CYP2B6 substrates and elucidate possible functional mechanisms of the influence of CYP2B6 polymorphisms on enzyme function and ADRs
Summary
Adverse drug reactions (ADRs) are globally one of the major causes of morbidity and mortality (Giardina et al, 2018; Patel and Patel, 2018). Drug clearance may vary up to 10-fold between two individuals of the same weight taking the same drug dosage (Stingl et al, 2013). This variation can be influenced by pathophysiological, physiological, or environmental factors. Genetic polymorphisms in drug transporters, drug targets and most importantly drug metabolizing enzymes have been emphasized over the years as one of the major factors causing variability in drug response (Weinshilboum, 2003; Evans and Relling, 2004)
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