Effect of antacids on the pharmacokinetics of raltegravir in human immunodeficiency virus-seronegative volunteers

Jennifer J. Kiser, J. Brock Bumpass, Amie L. Meditz, Peter L. Anderson, Lane Bushman, Michelle Ray, Julie A. Predhomme, Joseph Rower, Sam MaWhinney, Richard Brundage

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)4999-5003
Number of pages5
JournalAntimicrobial agents and chemotherapy
Volume54
Issue number12
DOIs
StatePublished - Dec 2010

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