Safety, tolerability, and pharmacokinetics of raltegravir after single and multiple doses in healthy subjects

Clin Pharmacol Ther. 2008 Feb;83(2):293-9. doi: 10.1038/sj.clpt.6100281. Epub 2007 Aug 22.


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 x 10 days), and (3) single-dose female study (400 mg). Raltegravir was rapidly absorbed with a terminal half-life (t1/2) approximately 7-12 h. Approximately 7-14% of raltegravir was excreted unchanged in urine. Area under the curve (AUC)(0-infinity) 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.

Publication types

  • Clinical Trial, Phase I
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Area Under Curve
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • HIV Integrase Inhibitors / administration & dosage*
  • HIV Integrase Inhibitors / adverse effects
  • HIV Integrase Inhibitors / pharmacokinetics
  • Half-Life
  • Humans
  • Male
  • Metabolic Clearance Rate
  • Organic Chemicals / administration & dosage*
  • Organic Chemicals / adverse effects
  • Organic Chemicals / pharmacokinetics
  • Pyrrolidinones
  • Raltegravir Potassium
  • Reference Values


  • HIV Integrase Inhibitors
  • Organic Chemicals
  • Pyrrolidinones
  • Raltegravir Potassium