Effect of Genetic Variations in Drug-Metabolizing Enzymes and Drug Transporters on the Pharmacokinetics of Rifamycins: A Systematic Review
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...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2022-06-01
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| Series: | Pharmacogenomics and Personalized Medicine |
| Subjects: | |
| Online Access: | https://www.dovepress.com/effect-of-genetic-variations-in-drug-metabolizing-enzymes-and-drug-tra-peer-reviewed-fulltext-article-PGPM |
| _version_ | 1818219207464058880 |
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| author | Sileshi T Mekonen G Makonnen E Aklillu E |
| author_facet | Sileshi T Mekonen G Makonnen E Aklillu E |
| author_sort | Sileshi T |
| collection | DOAJ |
| description | 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 tesemmasileshi@gmail.comAbstract: 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 |
| first_indexed | 2024-12-12T07:35:59Z |
| format | Article |
| id | doaj.art-1a9ce40d34cc453186624cfb6d37eaab |
| institution | Directory Open Access Journal |
| issn | 1178-7066 |
| language | English |
| last_indexed | 2024-12-12T07:35:59Z |
| publishDate | 2022-06-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Pharmacogenomics and Personalized Medicine |
| spelling | doaj.art-1a9ce40d34cc453186624cfb6d37eaab2022-12-22T00:32:55ZengDove Medical PressPharmacogenomics and Personalized Medicine1178-70662022-06-01Volume 1556157175737Effect of Genetic Variations in Drug-Metabolizing Enzymes and Drug Transporters on the Pharmacokinetics of Rifamycins: A Systematic ReviewSileshi TMekonen GMakonnen EAklillu ETesemma 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 tesemmasileshi@gmail.comAbstract: 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, transportershttps://www.dovepress.com/effect-of-genetic-variations-in-drug-metabolizing-enzymes-and-drug-tra-peer-reviewed-fulltext-article-PGPMrifamycinpharmacokineticspharmacogeneticsenzymestransporters |
| spellingShingle | Sileshi T Mekonen G Makonnen E Aklillu E Effect of Genetic Variations in Drug-Metabolizing Enzymes and Drug Transporters on the Pharmacokinetics of Rifamycins: A Systematic Review Pharmacogenomics and Personalized Medicine rifamycin pharmacokinetics pharmacogenetics enzymes transporters |
| title | Effect of Genetic Variations in Drug-Metabolizing Enzymes and Drug Transporters on the Pharmacokinetics of Rifamycins: A Systematic Review |
| title_full | Effect of Genetic Variations in Drug-Metabolizing Enzymes and Drug Transporters on the Pharmacokinetics of Rifamycins: A Systematic Review |
| title_fullStr | Effect of Genetic Variations in Drug-Metabolizing Enzymes and Drug Transporters on the Pharmacokinetics of Rifamycins: A Systematic Review |
| title_full_unstemmed | Effect of Genetic Variations in Drug-Metabolizing Enzymes and Drug Transporters on the Pharmacokinetics of Rifamycins: A Systematic Review |
| title_short | Effect of Genetic Variations in Drug-Metabolizing Enzymes and Drug Transporters on the Pharmacokinetics of Rifamycins: A Systematic Review |
| title_sort | effect of genetic variations in drug metabolizing enzymes and drug transporters on the pharmacokinetics of rifamycins a systematic review |
| topic | rifamycin pharmacokinetics pharmacogenetics enzymes transporters |
| url | https://www.dovepress.com/effect-of-genetic-variations-in-drug-metabolizing-enzymes-and-drug-tra-peer-reviewed-fulltext-article-PGPM |
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