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

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.

Figures

FIG. 1.

Mean (± standard deviations) RAL concentration-time curves with versus without an antacid. The numbers at 12, 24, and 48 h postdose correspond to the number of patients with detectable RAL concentrations at these time points. Values on the y axis represent the natural log of RAL concentrations. Values on the x axis represent times (hours) postdose.

FIG. 2.

Individual RAL concentration-time curves for subjects taking RAL alone (a) and the combination of RAL and antacid (b).

FIG. 3.

(a) Individual change in RAL AUC0-12 values with versus without an antacid. Geometric means are shown as shaded lines. (b) Individual Change in RAL C12 values with versus without an antacid. Geometric means are shown as shaded lines.