Lack of a significant drug interaction between raltegravir and tenofovir

Abstract

Raltegravir is a novel human immunodeficiency virus type 1 (HIV-1) integrase inhibitor with potent in vitro activity (95% inhibitory concentration of 31 nM in 50% human serum). This article reports the results of an open-label, sequential, three-period study of healthy subjects. Period 1 involved raltegravir at 400 mg twice daily for 4 days, period 2 involved tenofovir disoproxil fumarate (TDF) at 300 mg once daily for 7 days, and period 3 involved raltegravir at 400 mg twice daily plus TDF at 300 mg once daily for 4 days. Pharmacokinetic profiles were also determined in HIV-1-infected patients dosed with raltegravir monotherapy versus raltegravir in combination with TDF and lamivudine. There was no clinically significant effect of TDF on raltegravir. The raltegravir area under the concentration time curve from 0 to 12 h (AUC(0-12)) and peak plasma drug concentration (C(max)) were modestly increased in healthy subjects (geometric mean ratios [GMRs], 1.49 and 1.64, respectively). There was no substantial effect of TDF on raltegravir concentration at 12 h postdose (C(12)) in healthy subjects (GMR [TDF plus raltegravir-raltegravir alone], 1.03; 90% confidence interval [CI], 0.73 to 1.45), while a modest increase (GMR, 1.42; 90% CI, 0.89 to 2.28) was seen in HIV-1-infected patients. Raltegravir had no substantial effect on tenofovir pharmacokinetics: C(24), AUC, and C(max) GMRs were 0.87, 0.90, and 0.77, respectively. Coadministration of raltegravir and TDF does not change the pharmacokinetics of either drug to a clinically meaningful degree. Raltegravir and TDF may be coadministered without dose adjustments.

Figures

FIG. 1.

Arithmetic mean plasma raltegravir concentrations following multiple doses of raltegravir (RAL) at 400 mg twice daily with and without coadministration of multiple doses of TDF alone at 300 mg once daily or TDF at 300 mg once daily plus lamivudine (3TC) at 300 mg once daily. (A) Healthy young men (n = 9 [inset, semilog scale]). (B) Treatment-naïve HIV-positive patients (n = 6 [inset, semilog scale]).

FIG. 2.

Arithmetic mean serum tenofovir concentrations following multiple doses of TDF at 300 mg once daily with and without coadministration of multiple doses of raltegravir at 400 mg twice daily in healthy young men. Inset, semilog scale.