Abstract
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.
Keywords:
elbasvir; grazoprevir; hepatitis C virus; organic anion transporting polypeptide (OATP) 1B1; pharmacogenetics.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antiviral Agents / administration & dosage
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Antiviral Agents / blood*
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Antiviral Agents / therapeutic use
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Benzofurans / administration & dosage
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Benzofurans / blood*
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Benzofurans / therapeutic use
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Clinical Trials, Phase II as Topic
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Clinical Trials, Phase III as Topic
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Drug Combinations
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Female
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Hepacivirus / genetics
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Hepatitis C / drug therapy*
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Hepatitis C / genetics
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Humans
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Imidazoles / administration & dosage
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Imidazoles / blood*
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Imidazoles / therapeutic use
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Liver-Specific Organic Anion Transporter 1 / genetics*
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Logistic Models
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Male
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Middle Aged
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Pharmacogenetics
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Polymorphism, Single Nucleotide*
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Quinoxalines / administration & dosage
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Quinoxalines / blood*
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Quinoxalines / therapeutic use
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Retrospective Studies
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Treatment Outcome
Substances
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Antiviral Agents
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Benzofurans
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Drug Combinations
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Imidazoles
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Liver-Specific Organic Anion Transporter 1
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Quinoxalines
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SLCO1B1 protein, human
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elbasvir-grazoprevir drug combination