PMID- 24203510
OWN - NLM
STAT- MEDLINE
DCOM- 20150918
LR  - 20151119
IS  - 1552-4604 (Electronic)
IS  - 0091-2700 (Linking)
VI  - 54
IP  - 2
DP  - 2014 Feb
TI  - The effect of rilpivirine on the pharmacokinetics of methadone in HIV-negative 
      volunteers.
PG  - 133-40
LID - 10.1002/jcph.222 [doi]
AB  - 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.
CI  - (c) 2013, The American College of Clinical Pharmacology.
FAU - Crauwels, Herta M
AU  - Crauwels HM
AD  - From Janssen Infectious Diseases BVBA, Beerse, Belgium.
FAU - van Heeswijk, Rolf P G
AU  - van Heeswijk RP
FAU - Vandevoorde, Ann
AU  - Vandevoorde A
FAU - Buelens, Annemie
AU  - Buelens A
FAU - Stevens, Marita
AU  - Stevens M
FAU - Hoetelmans, Richard M W
AU  - Hoetelmans RM
LA  - eng
SI  - ClinicalTrials.gov/NCT00744770
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131123
PL  - England
TA  - J Clin Pharmacol
JT  - Journal of clinical pharmacology
JID - 0366372
RN  - 0 (Analgesics, Opioid)
RN  - 0 (Anti-HIV Agents)
RN  - 0 (Nitriles)
RN  - 0 (Pyrimidines)
RN  - FI96A8X663 (Rilpivirine)
RN  - UC6VBE7V1Z (Methadone)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Analgesics, Opioid/administration & dosage/blood/chemistry/*pharmacokinetics
MH  - Anti-HIV Agents/administration & dosage/adverse effects/*pharmacology
MH  - Drug Interactions
MH  - Drug Therapy, Combination/adverse effects
MH  - *HIV Seronegativity
MH  - Humans
MH  - Male
MH  - Methadone/adverse effects/blood/chemistry/*pharmacokinetics
MH  - Middle Aged
MH  - Nitriles/administration & dosage/adverse effects/*pharmacology
MH  - Opiate Substitution Treatment/adverse effects
MH  - Opioid-Related Disorders/drug therapy
MH  - Pyrimidines/administration & dosage/adverse effects/*pharmacology
MH  - Rilpivirine
MH  - Substance Withdrawal Syndrome/drug therapy
MH  - Volunteers
MH  - Young Adult
OTO - NOTNLM
OT  - methadone
OT  - non-nucleoside reverse transcriptase inhibitor
OT  - pharmacokinetics
OT  - rilpivirine
EDAT- 2013/11/10 06:00
MHDA- 2015/09/19 06:00
CRDT- 2013/11/09 06:00
PHST- 2013/04/11 00:00 [received]
PHST- 2013/10/31 00:00 [accepted]
PHST- 2013/11/09 06:00 [entrez]
PHST- 2013/11/10 06:00 [pubmed]
PHST- 2015/09/19 06:00 [medline]
AID - 10.1002/jcph.222 [doi]
PST - ppublish
SO  - J Clin Pharmacol. 2014 Feb;54(2):133-40. doi: 10.1002/jcph.222. Epub 2013 Nov 23.