title: The effect of rilpivirine on the pharmacokinetics of methadone in HIV-negative volunteers.
abstract: Antiretrovirals may influence methadone exposure in HIV-1-infected patients receiving methadone for opiate addiction. Rilpivirine is a non-nucleoside reverse transcriptase inhibitor for treating HIV-1 infection. In this open-label trial (NCT00744770), 13 HIV-negative volunteers continued on their regular stable methadone therapy (60 to 100 mg once daily; Days -14 to 12), with rilpivirine coadministration (Days 1 to 11). Methadone and rilpivirine pharmacokinetics and opiate withdrawal symptoms (Short Opiate Withdrawal Scale, Desires for Drugs Questionnaire, pupillometry) were evaluated. Rilpivirine decreased methadone minimum and maximum plasma concentrations (Cmin ; Cmax ) and area under the plasma concentration-time curve versus methadone alone (least-square mean ratio; 90% confidence interval) by 22% (0.78; 0.67, 0.91), 14% (0.86; 0.78, 0.95), and 16% (0.84; 0.74, 0.95), respectively (R-methadone), and 21% (0.79; 0.67, 0.92), 13% (0.87; 0.78, 0.97), and 16% (0.84; 0.74, 0.96), respectively (S-methadone). Rilpivirine pharmacokinetics with methadone were consistent with historic data. No clinically relevant opiate withdrawal symptoms were reported. Methadone and rilpivirine coadministration was generally well tolerated. No grade 3/4 adverse events (AEs), serious AEs, or discontinuations due to AEs were seen. No methadone dose adjustment is prompted by rilpivirine coadministration. Clinical monitoring for opiate withdrawal is recommended, as some patients may require adjustment of methadone maintenance therapy.
authors.affiliation: From Janssen Infectious Diseases BVBA, Beerse, Belgium.
authors.forename: Herta M
authors.initials: HM
authors.lastname: Crauwels
authors.forename: Rolf P G
authors.initials: RP
authors.lastname: van Heeswijk
authors.forename: Ann
authors.initials: A
authors.lastname: Vandevoorde
authors.forename: Annemie
authors.initials: A
authors.lastname: Buelens
authors.forename: Marita
authors.initials: M
authors.lastname: Stevens
authors.forename: Richard M W
authors.initials: RM
authors.lastname: Hoetelmans
mesh_terms: D000293:Adolescent; D000328:Adult; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D004347:Drug Interactions; D004359:Drug Therapy, Combination / Q000009:adverse effects; D018023:HIV Seronegativity; D006801:Humans; D008297:Male; D008691:Methadone / Q000009:adverse effects / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D008875:Middle Aged; D009570:Nitriles / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D058850:Opiate Substitution Treatment / Q000009:adverse effects; D009293:Opioid-Related Disorders / Q000188:drug therapy; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D000068696:Rilpivirine; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy; D014838:Volunteers; D055815:Young Adult
chemical_list: D000701:Analgesics, Opioid; D019380:Anti-HIV Agents; D009570:Nitriles; D011743:Pyrimidines; D000068696:Rilpivirine; D008691:Methadone
keywords: methadone; non-nucleoside reverse transcriptase inhibitor; pharmacokinetics; rilpivirine