PMID- 22682979
OWN - NLM
STAT- MEDLINE
DCOM- 20130408
LR  - 20151119
IS  - 1879-0046 (Electronic)
IS  - 0376-8716 (Linking)
VI  - 126
IP  - 1-2
DP  - 2012 Nov 1
TI  - Effect of lersivirine co-administration on pharmacokinetics of methadone in 
      healthy volunteers.
PG  - 183-8
LID - S0376-8716(12)00172-X [pii]
LID - 10.1016/j.drugalcdep.2012.05.009 [doi]
AB  - BACKGROUND: Lersivirine is a next-generation non-nucleoside reverse transcriptase 
      inhibitor under development for the treatment of HIV-1 infection. HIV-1-infected 
      patients receiving methadone may have a limited choice of antiretroviral agents 
      due to drug-drug interactions. As methadone is metabolized by CYP3A4 and 
      lersivirine is a weak CYP3A4 inducer, it is possible that lersivirine may 
      decrease methadone concentrations. This study evaluated the effect of lersivirine 
      on the pharmacokinetics (PK) of R- and S-methadone enantiomers. METHODS: An 
      open-label, single-sequence study was performed in 13 HIV-negative volunteers 
      receiving stable methadone maintenance therapy (MMT) (50-150 mg QD) for >/=3 
      months. Healthy volunteers received their methadone to steady-state on day 1 and 
      lersivirine (1000 mg QD) plus their same methadone dose on Days 2-11. Assessments 
      included PK, safety, short opiate withdrawal scale (SOWS), desires for drugs 
      questionnaire (DDQ) and pupillary diameter measurements (PDMs). RESULTS: 
      Following administration of methadone alone or in combination with lersivirine, 
      R- and S-methadone concentrations did not appear different (ratios of adjusted 
      geometric means for PK parameters: 95-104%). Following co-administration of 
      lersivirine and methadone, adverse events (AEs) were generally mild to moderate 
      in severity. One patient discontinued due to nausea. An examination of objective 
      (vital signs, AEs, PDM), subjective (SOWS and DDQ scores) and PK data suggested 
      that subjects did not experience opioid withdrawal during the study. CONCLUSIONS: 
      Co-administration of lersivirine (1000 mg QD) with methadone did not result in 
      clinically relevant changes in R-/S-methadone concentrations or opioid withdrawal 
      symptoms. No methadone dose adjustment is required when lersivirine is 
      administered alongside MMT.
CI  - Copyright (c) 2012 Elsevier Ireland Ltd. All rights reserved.
FAU - Vourvahis, Manoli
AU  - Vourvahis M
AD  - Pfizer Global Research and Development, New York, NY 10017, USA. 
      manoli.vourvahis@pfizer.com
FAU - Wang, Rong
AU  - Wang R
FAU - Gruener, Daniel Mark
AU  - Gruener DM
FAU - Bruce, R Douglas
AU  - Bruce RD
FAU - Haider, Seema
AU  - Haider S
FAU - Tawadrous, Margaret
AU  - Tawadrous M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120608
PL  - Ireland
TA  - Drug Alcohol Depend
JT  - Drug and alcohol dependence
JID - 7513587
RN  - 0 (Anti-HIV Agents)
RN  - 0 (Narcotics)
RN  - 0 (Nitriles)
RN  - 0 (Pyrazoles)
RN  - 0 (Reverse Transcriptase Inhibitors)
RN  - 0 (UK 453,061)
RN  - UC6VBE7V1Z (Methadone)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Anti-HIV Agents/adverse effects/*pharmacology
MH  - Area Under Curve
MH  - Chromatography, High Pressure Liquid
MH  - Drug Interactions
MH  - Female
MH  - Humans
MH  - Male
MH  - Methadone/chemistry/*pharmacokinetics
MH  - Middle Aged
MH  - Narcotics/chemistry/*pharmacokinetics
MH  - Nitriles/adverse effects/*pharmacology
MH  - Pupil/drug effects
MH  - Pyrazoles/adverse effects/*pharmacology
MH  - Reverse Transcriptase Inhibitors/adverse effects/*pharmacology
MH  - Stereoisomerism
MH  - Substance Withdrawal Syndrome/psychology
MH  - Surveys and Questionnaires
MH  - Tandem Mass Spectrometry
MH  - Young Adult
EDAT- 2012/06/12 06:00
MHDA- 2013/04/09 06:00
CRDT- 2012/06/12 06:00
PHST- 2011/08/16 00:00 [received]
PHST- 2012/01/13 00:00 [revised]
PHST- 2012/05/11 00:00 [accepted]
PHST- 2012/06/12 06:00 [entrez]
PHST- 2012/06/12 06:00 [pubmed]
PHST- 2013/04/09 06:00 [medline]
AID - S0376-8716(12)00172-X [pii]
AID - 10.1016/j.drugalcdep.2012.05.009 [doi]
PST - ppublish
SO  - Drug Alcohol Depend. 2012 Nov 1;126(1-2):183-8. doi: 
      10.1016/j.drugalcdep.2012.05.009. Epub 2012 Jun 8.