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Eley T, He B, Huang SP, et al. Pharmacokinetics of the NS3 Protease Inhibitor, Asunaprevir (ASV, BMS-650032), in Phase I Studies in Subjects With or Without Chronic Hepatitis C. Clin Pharmacol Drug Dev. 2013;2(4):316-27doi: 10.1002/cpdd.52.
Eley, T., He, B., Huang, S. P., Li, W., Pasquinelli, C., Rodrigues, A. D., Grasela, D. M., & Bertz, R. J. (2013). Pharmacokinetics of the NS3 Protease Inhibitor, Asunaprevir (ASV, BMS-650032), in Phase I Studies in Subjects With or Without Chronic Hepatitis C. Clinical pharmacology in drug development, 2(4), 316-27. https://doi.org/10.1002/cpdd.52
Eley, Timothy, et al. "Pharmacokinetics of the NS3 Protease Inhibitor, Asunaprevir (ASV, BMS-650032), in Phase I Studies in Subjects With or Without Chronic Hepatitis C." Clinical pharmacology in drug development vol. 2,4 (2013): 316-27. doi: https://doi.org/10.1002/cpdd.52
Eley T, He B, Huang SP, Li W, Pasquinelli C, Rodrigues AD, Grasela DM, Bertz RJ. Pharmacokinetics of the NS3 Protease Inhibitor, Asunaprevir (ASV, BMS-650032), in Phase I Studies in Subjects With or Without Chronic Hepatitis C. Clin Pharmacol Drug Dev. 2013 Oct;2(4):316-27. doi: 10.1002/cpdd.52. Epub 2013 Aug 16. PMID: 27121936.
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Clin Pharmacol Drug Dev. 2013 Oct;2(4):316-27. doi: 10.1002/cpdd.52. Epub 2013 Aug 16.

Pharmacokinetics of the NS3 Protease Inhibitor, Asunaprevir (ASV, BMS-650032), in Phase I Studies in Subjects With or Without Chronic Hepatitis C.

Clinical pharmacology in drug development

Timothy Eley, Bing He, Shu-Pang Huang, Wenying Li, Claudio Pasquinelli, A David Rodrigues, Dennis M Grasela, Richard J Bertz

Affiliations

  1. Bristol-Myers Squibb, Research and Development, Hopewell, NJ, USA.
  2. Bristol-Myers Squibb, Research and Development, Princeton, NJ, USA.

PMID: 27121936 DOI: 10.1002/cpdd.52

Abstract

Asunaprevir (BMS-650032, ASV) is a potent, selective hepatitis C virus (HCV) NS3 protease inhibitor in clinical evaluation for chronic hepatitis C treatment. ASV pharmacokinetics were evaluated in four single- and multiple-ascending-dose studies in healthy subjects or subjects with HCV genotype 1 infection and in human mass balance and food-effect studies. Median Tmax was 2-4 hours. Although T½ was 14-23 hours, oral clearance was high (302-668 L/h at doses ≥100 mg). Steady state was achieved by Day 7. The ASV dose-exposure relationship was disproportionate at doses <200 mg but largely proportional for Cmax and AUC at clinically relevant doses of 200-600 mg (capsule). Following multiple doses, the accumulation index for AUC[TAU] and Cmin was lower at doses ≥200 mg, suggestive of possible auto-induction. ASV exposure increased when administered as a solution (vs. suspension) or with a high-fat meal; the effect was greater for Cmax than AUC, suggesting a saturable first-pass process, the mechanism of which remains to be defined. The apparent complexities of ASV pharmacokinetics will be further explored; nevertheless, data from these studies and antiviral activity in phase 2a/2b studies support further development. Clinical studies are ongoing with ASV in combination with other antivirals.

© 2013, The American College of Clinical Pharmacology.

Keywords: NS3; asunaprevir; hepatitis C virus; pharmacokinetics

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