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Pharmacokinetics of Once-Daily Boosted Elvitegravir When Administered in Combination With Acid-Reducing Agents

Ramanathan, Srinivasan PhD; Mathias, Anita PhD; Wei, Xuelian PhD; Shen, Gong PhD; Koziara, Joanna PhD; Cheng, Andrew MD, PhD; Kearney, Brian P. PharmD

JAIDS Journal of Acquired Immune Deficiency Syndromes: September 1st, 2013 - Volume 64 - Issue 1 - p 45–50
doi: 10.1097/QAI.0b013e31829ecd3b
Clinical Science

Background: Acid-reducing agents are commonly used co-medications by HIV-1–infected patients receiving antiretroviral treatment. The effects of various representative acid-reducing agents on the pharmacokinetics (PK) of boosted elvitegravir were evaluated by 1-way interaction in 4 studies.

Methods: Healthy subjects received ritonavir-boosted elvitegravir (EVG/r; 50/100 mg QD) administered alone or with antacid simultaneously in Study 1, staggered (±2 or ±4 hours) or with omeprazole in Study 2; Studies 3 and 4 evaluated cobicistat-boosted elvitegravir (EVG/co; 150/150 mg QD) administered simultaneously or staggered (+12 hours) with famotidine or omeprazole. Lack of PK alteration was defined as 90% confidence intervals about the geometric least squares means ratio (coadministration:alone) being within 70%–143% for elvitegravir Cmax (maximum concentration), Ctau (trough), and AUCtau (area under plasma concentration–time curve; 0–24 hours); cobicistat PK were explored.

Results: EVG exposures were 40%–50% lower upon simultaneous dosing of EVG/r and antacids, probably due to local complexation with cations in gastrointestinal tract, and were unaffected with ≥2 hours staggered dosing. No relevant drug interactions were observed between EVG/co and famotidine or between EVG/r or EVG/co and omeprazole, indicating the absence of a broader pH effect on boosted EVG PK. In all studies, study treatments were well tolerated, with adverse events being generally mild to moderate in severity and primarily gastrointestinal disorders.

Conclusions: There are no clinically relevant interactions between boosted elvitegravir, and thus elvitegravir/cobicistat/emtricitabine/tenofovir DF single-tablet regimen, and H2-receptor antagonists or proton pump inhibitors; staggered antacid administration by ≥2 hours is recommended.

Clinical Research, Gilead Sciences, Inc, Foster City, CA.

Correspondence to: Srinivasan Ramanathan, PhD, Gilead Sciences, Inc, 333 Lakeside Drive, Foster City, CA 94404 (e-mail:

Supported by Gilead Sciences, Inc.

Presented at the Fifth International Workshop on Clinical Pharmacology of HIV Therapy, April 16–18, 2007, Budapest and 12th International Workshop on Clinical Pharmacology of HIV Therapy, April 13–15, 2011, Miami, FL.

All authors are or were employees of Gilead Sciences, Inc. The authors have no remaining conflicts of interest to disclose.

Informed consent was obtained from all subjects. These studies were performed in compliance with current Good Clinical Practice (GCP) and were conducted by MDS Pharma Services, Phoenix, AZ (Study 1), Charles River Laboratories (formerly Northwest Kinetics), Tacoma, WA (Study 2), or SeaView Research, Inc, Miami, FL (Studies 3 and 4) under the review of the Institutional Review Boards whose operations are in compliance with Section 56 of Title 21 of the Code of Federal Regulations (CFR).

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Received February 25, 2013

Accepted April 29, 2013

© 2013 by Lippincott Williams & Wilkins