Pharmacogenetic analysis of OATP1B1 variants in relation to the pharmacokinetics of Grazoprevir and the efficacy of Zepatier (Elbasvir and Grazoprevir) in HCV infected subjects from previously conducted clinical studies

Guo, Zifang; Caro, Luzelena; Robertson, Michael; McCrea, Jacqueline B.; Hoover, Patricia A.; Wudarski, Christen; Maiuri, Kristina; Wang, Yinghong; Mogg, Robin; Mehrotra, Devan V.; Blanchard, Rebecca; Shaw, Peter M.

doi:10.1016/j.dmpk.2017.11.279

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Drug Metabolism and Pharmacokinetics

2018

DOI: 10.1016/j.dmpk.2017.11.279

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Pharmacogenetic analysis of OATP1B1 variants in relation to the pharmacokinetics of Grazoprevir and the efficacy of Zepatier (Elbasvir and Grazoprevir) in HCV infected subjects from previously conducted clinical studies

Zifang Guo

Luzelena Caro

Michael Robertson

et al.

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The Pharmacogenetics of OATP1B1 Variants and their impact on the Pharmacokinetics and Efficacy of Elbasvir/Grazoprevir

et al. 2019

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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.

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The Pharmacogenetics of OATP1B1 Variants and their impact on the Pharmacokinetics and Efficacy of Elbasvir/Grazoprevir

et al. 2019

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Pharmacogenetic analysis of OATP1B1 variants in relation to the pharmacokinetics of Grazoprevir and the efficacy of Zepatier (Elbasvir and Grazoprevir) in HCV infected subjects from previously conducted clinical studies

Cited by 1 publication

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The Pharmacogenetics of OATP1B1 Variants and their impact on the Pharmacokinetics and Efficacy of Elbasvir/Grazoprevir

The Pharmacogenetics of OATP1B1 Variants and their impact on the Pharmacokinetics and Efficacy of Elbasvir/Grazoprevir

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