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 h×10 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.

Clinical Pharmacology & Therapeutics (2008) doi:10.1038/sj.clpt.6100281