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The Effects of Boceprevir and Telaprevir on the Pharmacokinetics of Maraviroc: An Open-Label, Fixed-Sequence Study in Healthy Volunteers

Vourvahis, Manoli PharmD*; Plotka, Anna MSc; Kantaridis, Constantino MD; Fang, Annie MD, PhD§; Heera, Jayvant MD

JAIDS Journal of Acquired Immune Deficiency Syndromes: April 15th, 2014 - Volume 65 - Issue 5 - p 564–570
doi: 10.1097/QAI.0000000000000090
Clinical Science

Objective: To evaluate the effects of boceprevir (BOC) and telaprevir (TVR) on the pharmacokinetics (PK) of maraviroc (MVC) in healthy volunteers.

Methods: In this open-label, fixed-sequence study, 14 volunteers received MVC 150 mg twice daily alone for 5 days (period 1), followed by MVC + BOC 800 mg 3 times daily and MVC + TVR 750 mg 3 times daily, each for 10 days in periods 2 and 3, respectively, with a ≥10-day wash-out. PK was analyzed on day 5 of period 1 and day 10 of periods 2 and 3. Safety was also assessed.

Results: Ratios of the adjusted geometric means (90% confidence intervals) for MVC area under the curve from predose to 12 hours, maximum plasma concentration, and plasma concentration at 12 hours were 3.02 (2.53 to 3.59), 3.33 (2.54 to 4.36), and 2.78 (2.40 to 3.23), respectively, for MVC + BOC versus MVC alone, and 9.49 (7.94 to 11.34), 7.81 (5.92 to 10.32), and 10.17 (8.73 to 11.85), respectively, for MVC + TVR versus MVC alone. PK profiles for MVC + BOC or TVR were consistent with historic values for BOC and TVR monotherapy. Adverse event incidence was higher with MVC + BOC and MVC + TVR versus MVC alone. Dysgeusia (50%) and pruritus (29%) occurred most commonly with MVC + BOC, and fatigue (46%) and headache (31%) with MVC + TVR. There were no serious adverse events.

Conclusions: MVC exposures were significantly increased with BOC or TVR, therefore MVC should be dosed at 150 mg twice daily when coadministered with these newly approved hepatitis C protease inhibitors. No dose adjustment for BOC or TVR is warranted with MVC. MVC + BOC or TVR was generally well tolerated with no unexpected safety findings.

*Clinical Pharmacology, Pfizer Inc, New York, NY;

Statistics, Pfizer Inc, Collegeville, PA;

Pfizer Clinical Research Unit, Brussels, Belgium;

§Clinical Development, Pfizer Inc, New York, NY; and

Clinical Development, Pfizer Inc, Groton, CT.

Correspondence to: Manoli Vourvahis, PharmD, Pfizer Global Research and Development, 219 East 42nd Street, New York, NY 10017 (e-mail: manoli.vourvahis@pfizer.com).

Supported by ViiV Healthcare and managed by Pfizer Inc.

Presented at the 14th International Workshop on Clinical Pharmacology of HIV, April 23, 2013, Amsterdam, the Netherlands.

M.V., A.P., C.K., A.F., and J.H. are employees of Pfizer, Inc and hold stock/stock options in Pfizer, Inc.

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially. http://creativecommons.org/licenses/by-nc-nd/3.0.

Received August 08, 2013

Accepted December 03, 2013

© 2014 by Lippincott Williams & Wilkins