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Antimicrob Agents Chemother. 2011 Oct;55(10):4569-74. doi: 10.1128/AAC.00653-11. Epub 2011 Aug 08.

Effect of the hepatitis C virus protease inhibitor telaprevir on the pharmacokinetics of amlodipine and atorvastatin.

Antimicrobial agents and chemotherapy

Jee Eun Lee, Rolf van Heeswijk, Katia Alves, Frances Smith, Varun Garg

Affiliations

  1. Vertex Pharmaceuticals Incorporated, 130 Waverly Street, Cambridge, MA 02139-4242, USA.

PMID: 21825288 PMCID: PMC3187007 DOI: 10.1128/AAC.00653-11

Abstract

Telaprevir is a hepatitis C virus protease inhibitor that is both a substrate and an inhibitor of CYP3A. Amlodipine and atorvastatin are both substrates of CYP3A and are among the drugs most frequently used by patients with hepatitis C. This study was conducted to examine the effect of telaprevir on atorvastatin and amlodipine pharmacokinetics (PK). This was an open-label, single sequence, nonrandomized study involving 21 healthy male and female volunteers. A coformulation of 5 mg amlodipine and 20 mg atorvastatin was administered on day 1. Telaprevir was taken with food as a 750-mg dose every 8 h from day 11 until day 26, and a single dose of the amlodipine-atorvastatin combination was readministered on day 17. Plasma samples were collected for determination of the PK of telaprevir, amlodipine, atorvastatin, ortho-hydroxy atorvastatin, and para-hydroxy atorvastatin. When administration with telaprevir was compared with administration without telaprevir, the least-square mean ratios (90% confidence limits) for amlodipine were 1.27 (1.21, 1.33) for the maximum drug concentration in serum (C(max)) and 2.79 (2.58, 3.01) for the area under the concentration-time curve from 0 h to infinity (AUC(0-∞)); for atorvastatin, they were 10.6 (8.74, 12.9) for the C(max) and 7.88 (6.84, 9.07) for the AUC(0-∞). Telaprevir significantly increased exposure to amlodipine and atorvastatin, consistent with the inhibitory effect of telaprevir on the CYP3A-mediated metabolism of these agents.

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