Pharmacogenomics and Personalized Medicine (Jun 2022)
Effect of Genetic Variations in Drug-Metabolizing Enzymes and Drug Transporters on the Pharmacokinetics of Rifamycins: A Systematic Review
Abstract
Tesemma Sileshi,1,2 Gosaye Mekonen,1 Eyasu Makonnen,2,3 Eleni Aklillu4 1Department of Pharmacy, Ambo University, Ambo, Ethiopia; 2Department of Pharmacology and Clinical Pharmacy, Addis Ababa University, Addis Ababa, Ethiopia; 3Center for Innovative Drug Development and Therapeutic Trials for Africa (CDT-Africa), Addis Ababa University, Addis Ababa, Ethiopia; 4Department of Laboratory Medicine, Karolinska Institutet, Stockholm, SwedenCorrespondence: Tesemma Sileshi, Department of Pharmacy, Ambo University, P.O Box 19, Ambo, Ethiopia, Tel +2510911550975, Email [email protected]: Background: Rifamycins are a novel class of antibiotics clinically approved for tuberculosis chemotherapy. They are characterized by high inter-individual variation in pharmacokinetics. This systematic review aims to present the contribution of genetic variations in drug-metabolizing enzymes and transporter proteins to the inter-individual variation of rifamycin pharmacokinetics.Method: We followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement guidelines. The search for relevant studies was done through PubMed, Embase, Web of Science, and Scopus databases. Studies reporting single nucleotide polymorphism in drug transporters and metabolizing enzymes’ influence on rifamycin pharmacokinetics were solely included. Two reviewers independently performed data extraction.Results: The search identified 117 articles of which 15 fulfilled the eligibility criteria and were included in the final data synthesis. The single nucleotides polymorphism in the drug transporters SLCO1B1 rs4149032, rs2306283, rs11045819, and ABCB1 rs1045642 for rifampicin, drug metabolizing enzyme AADAC rs1803155 for rifapentine and CES2 c.-22263A>G (g.738A>G) for rifampicin partly contributes to the variability of pharmacokinetic parameters in tuberculosis patients.Conclusion: The pharmacokinetics of rifamycins is influenced by genetic variation of drug-metabolizing enzymes and transporters. Controlled clinical studies are, however, required to establish these relationships.Keywords: rifamycin, pharmacokinetics, pharmacogenetics, enzymes, transporters
