title: Effect of raltegravir on the pharmacokinetics of methadone.
abstract: A randomized, placebo-controlled, 2-period crossover study in subjects on methadone maintenance therapy was conducted to assess the effect of the HIV-1 integrase inhibitor, raltegravir, on the pharmacokinetics of methadone. Twelve HIV-negative male and female subjects stabilized on an oral methadone program were enrolled. Subjects maintained their prescribed oral doses of methadone throughout the study and, in each of 2 periods, received either 400 mg of raltegravir or matching placebo every 12 hours on days 1 through 10 of each treatment period with a washout of 7 days between periods. Plasma samples for analysis of methadone pharmacokinetics were collected over 24 hours postdose on day 10 of each treatment period. Safety and tolerability were assessed throughout the study. The geometric mean ratio (90% confidence interval) for methadone when administered with raltegravir relative to methadone alone was 1.00 (0.93-1.09) for area under the methadone concentration time curve from time 0 to 24 hours and 1.00 (0.94-1.07) for maximal concentration. There were no serious clinical or laboratory adverse experiences. There were no discontinuations due to an adverse experience. Coadministration of raltegravir and methadone is generally well tolerated. Raltegravir has no clinically meaningful effect on methadone pharmacokinetics. No dose adjustment is required for methadone when coadministered with raltegravir.
authors.affiliation: Merck & Co., Inc., Whitehouse Station, NJ, USA. matt_anderson@merck.com
authors.forename: Matt S
authors.initials: MS
authors.lastname: Anderson
authors.forename: Julie Ann
authors.initials: JA
authors.lastname: Mabalot Luk
authors.forename: William D
authors.initials: WD
authors.lastname: Hanley
authors.forename: Bo
authors.initials: B
authors.lastname: Jin
authors.forename: Robert A
authors.initials: RA
authors.lastname: Riesenberg
authors.forename: Larissa A
authors.initials: LA
authors.lastname: Wenning
authors.forename: Jeffery A
authors.initials: JA
authors.lastname: Chodakewitz
authors.forename: John A
authors.initials: JA
authors.lastname: Wagner
authors.forename: Marian
authors.initials: M
authors.lastname: Iwamoto
mesh_terms: D000293:Adolescent; D000328:Adult; D018592:Cross-Over Studies; D004347:Drug Interactions; D005260:Female; D019428:HIV Integrase Inhibitors / Q000009:adverse effects / Q000494:pharmacology*; D006801:Humans; D007536:Isomerism; D008297:Male; D008691:Methadone / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008875:Middle Aged; D058850:Opiate Substitution Treatment; D009293:Opioid-Related Disorders / Q000097:blood / Q000188:drug therapy; D011760:Pyrrolidinones / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D000068898:Raltegravir Potassium; D055815:Young Adult
chemical_list: D019428:HIV Integrase Inhibitors; D011760:Pyrrolidinones; D000068898:Raltegravir Potassium; D008691:Methadone