Effect of Antacids on the Pharmacokinetics of Raltegravir in Human Immunodeficiency Virus-Seronegative Volunteers

Author:

Kiser Jennifer J.1,Bumpass J. Brock12,Meditz Amie L.1,Anderson Peter L.1,Bushman Lane1,Ray Michelle1,Predhomme Julie A.1,Rower Joseph1,MaWhinney Sam1,Brundage Richard3

Affiliation:

1. University of Colorado Denver, Aurora, Colorado

2. Campbell University College of Pharmacy and Health Sciences, Buies Creek, North Carolina

3. University of Minnesota, Minneapolis, Minnesota

Abstract

ABSTRACT Raltegravir's divalent metal ion chelating motif may predispose the drug to interactions with divalent cations. We determined whether a divalent cation-containing antacid interacted with raltegravir. Twelve HIV-1-seronegative subjects were enrolled in this randomized, prospective, crossover study of single-dose raltegravir (400 mg) with and without an antacid. Subjects underwent two intensive pharmacokinetic visits in the fasted state separated by a 5- to 12-day washout period. With simultaneous antacid administration, time to peak raltegravir concentration occurred 2 h sooner ( P = 0.002) and there was a 67% lower raltegravir concentration at 12 h postdose ( P < 0.0001) than with administration of raltegravir alone. The raltegravir area under the-concentration-time curve from 0 to 12 h and maximum concentration were unchanged with the addition of an antacid. Studies are needed to determine the clinical relevance of this interaction, whether it remains after multiple dosing to steady state, whether it is mitigated by temporal separation, and whether raltegravir interacts with divalent cation-containing vitamins, supplements, or foods.

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

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