The pharmacogenetics of OATP1B1 variants and their impact on the pharmacokinetics and efficacy of elbasvir/grazoprevir
| Autor: | Rebecca L. Blanchard, Devan V. Mehrotra, Robin Mogg, Luzelena Caro, Peter M. Shaw, Michael N. Robertson, Kristina Maiuri, Patricia A. Hoover, Christen Wudarski, Zifang Guo, Ying-Hong Wang, Peggy Hwang |
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| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Oncology medicine.medical_specialty Elbasvir Hepatitis C virus Hepacivirus medicine.disease_cause Antiviral Agents Polymorphism Single Nucleotide 030226 pharmacology & pharmacy 03 medical and health sciences Clinical Trials Phase II as Topic 0302 clinical medicine Pharmacokinetics Quinoxalines Internal medicine Genetics medicine Humans Elbasvir Grazoprevir Benzofurans Retrospective Studies Pharmacology biology Liver-Specific Organic Anion Transporter 1 business.industry Imidazoles Hepatitis C Middle Aged medicine.disease Drug Combinations Logistic Models Treatment Outcome 030104 developmental biology Clinical Trials Phase III as Topic Grazoprevir Pharmacogenetics biology.protein Molecular Medicine Female business SLCO1B1 |
| Zdroj: | Pharmacogenomics. 20:631-641 |
| ISSN: | 1744-8042 1462-2416 |
| DOI: | 10.2217/pgs-2019-0022 |
| Popis: | Aim: To evaluate the effect of SLCO1B1 genetic variants on grazoprevir pharmacokinetics and efficacy. Methods: A retrospective analysis of 1578 hepatitis C virus-infected participants from ten Phase II/III clinical trials. Results: Relative to noncarriers of the risk allele, geometric mean ratios (95% CI) of grazoprevir area under curve (AUC)0–24 were: rs4149056 (risk allele C), one copy, 1.13 (1.06–1.21), two copies, 1.43 (1.16–1.77); and rs11045819 (risk allele A), one copy, 0.93 (0.87–1.00); two copies, 0.78 (0.61–1.00). The rs2306283 variant was not associated with grazoprevir exposure. None of the SLCO1B1 variants were associated with sustained virologic response. Conclusion: Genetic variants in SLCO1B1 were associated with modest changes in grazoprevir pharmacokinetics, but not with meaningful differences in efficacy. |
| Databáze: | OpenAIRE |
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