1. ¹Departments of Clinical Pharmacology, Clinical Drug Metabolism, Clinical Biostatistics, and Medical Communications, Merck Research Laboratories, a division of Merck & Co., Inc., Whitehouse Station, NJ, USA
2. ²SGS Life Sciences Services, Antwerp, Belgium
3. ³Pharmanet Development Group, Miami, Florida, USA

Correspondence: M Iwamoto, (marian_iwamoto@merck.com)

Received 22 March 2007; Accepted 29 May 2007; Published online 22 August 2007.

Abstract

Raltegravir is a novel human immunodeficiency virus-1 integrase inhibitor with potent in vitro activity (95% inhibitory concentration (IC₉₅)=33 nM in 50% human serum). Three double-blind, randomized, placebo-controlled, pharmacokinetic, safety, and tolerability studies were conducted: (1) single-dose escalation study (10–1,600 mg), (2) multiple-dose escalation study (100–800 mg q12 h10 days), and (3) single-dose female study (400 mg). Raltegravir was rapidly absorbed with a terminal half-life (t_½) 7–12 h. Approximately 7–14% of raltegravir was excreted unchanged in urine. Area under the curve (AUC)_0– was similar between male and female subjects. After multiple-dose administration, steady state was achieved within 2 days; there was little to modest accumulation of raltegravir. Trough levels were >33 nM for dose levels of 100 mg and greater. Raltegravir is generally well tolerated at doses of up to 1,600 mg/day given for up to 10 days and exhibits a pharmacokinetic profile supportive of twice-daily dosing with multiple doses of 100 mg and greater achieving trough levels >33 nM.