title: Clinical pharmacology profile of raltegravir, an HIV-1 integrase strand transfer inhibitor.
abstract: Raltegravir is an HIV-1 integrase inhibitor approved to treat HIV infection in adults in combination with other antiretrovirals. Data from healthy volunteers demonstrate that raltegravir is rapidly absorbed with a mean half-life of approximately 7 to 12 hours, with steady state achieved in approximately 2 days. Raltegravir is characterized by both high intra- and interindividual variabilities, although neither gender, race, age, body mass index, food intake, nor renal or hepatic insufficiency has a clinically meaningful effect on raltegravir pharmacokinetics. Raltegravir lacks activity as a perpetrator of drug-drug interactions and demonstrates a low propensity to be subject to drug-drug interactions. Raltegravir is metabolized primarily by UGT1A1 and is not affected by P450 inhibitors or inducers. Inhibitors of UGT1A1 (eg, atazanavir) can increase plasma concentrations of raltegravir, although this increase has not been found to be clinically meaningful. Likewise, inducers of UGT1A1 (eg, rifampin) can reduce plasma concentrations of raltegravir, and the clinical significance of this reduction is being investigated in ongoing clinical studies. Raltegravir demonstrates favorable clinical pharmacology and a drug interaction profile that permits administration to a wide, demographically diverse patient population and coadministration with many other therapeutic agents, including antiretroviral agents and supportive medications, without restrictions or dose adjustment.
authors.affiliation: Merck Sharp & Dohme Corp, Whitehouse Station, New Jersey, USA.
authors.forename: Diana M
authors.initials: DM
authors.lastname: Brainard
authors.forename: Larissa A
authors.initials: LA
authors.lastname: Wenning
authors.forename: Julie A
authors.initials: JA
authors.lastname: Stone
authors.forename: John A
authors.initials: JA
authors.lastname: Wagner
authors.forename: Marian
authors.initials: M
authors.lastname: Iwamoto
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology*; D019540:Area Under Curve; D015658:HIV Infections / Q000188:drug therapy*; D019427:HIV Integrase / Q000378:metabolism*; D006801:Humans; D011760:Pyrrolidinones / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D000068898:Raltegravir Potassium
chemical_list: D019380:Anti-HIV Agents; D011760:Pyrrolidinones; D000068898:Raltegravir Potassium; D019427:HIV Integrase; C514801:p31 integrase protein, Human immunodeficiency virus 1