Format

Send to

Choose Destination
Pharmacogenomics. 2019 Jun;20(9):631-641. doi: 10.2217/pgs-2019-0022.

The pharmacogenetics of OATP1B1 variants and their impact on the pharmacokinetics and efficacy of elbasvir/grazoprevir.

Author information

1
Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ 07033, USA.
2
At time of writing: Merck & Co., Inc., Kenilworth, NJ 07033, USA.
3
At time of publication: Bill & Melinda Gates Medical Research Institute, 625 Massachusetts Ave, Cambridge, MA 02139-3357, USA.
4
At time of publication: CRISPR Therapeutics, 610 Main Street Cambridge, MA 02139, USA.

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

PMID:
31250727
DOI:
10.2217/pgs-2019-0022

Supplemental Content

Full text links

Icon for Atypon
Loading ...
Support Center