PMID- 17379053
OWN - NLM
STAT- MEDLINE
DCOM- 20070807
LR  - 20181201
IS  - 0149-2918 (Print)
IS  - 0149-2918 (Linking)
VI  - 29
IP  - 1
DP  - 2007 Jan
TI  - Effects of pegylated interferon alfa-2b on the pharmacokinetic and 
      pharmacodynamic properties of methadone: a prospective, nonrandomized, crossover 
      study in patients coinfected with hepatitis C and HIV receiving methadone 
      maintenance treatment.
PG  - 131-8
AB  - BACKGROUND: Hepatitis C virus (HCV) infection is common among 
      methadone-maintained HIV-positive individuals. Pegylated interferon (pegIFN) used 
      in combination with ribavirin is conventional treatment for HCV. However, pegIFN 
      has been associated with adverse effects (AEs) that may simulate opioid 
      withdrawal and be confused with insufficient methadone dosage. OBJECTIVE: The aim 
      of this study was to determine, using methadone pharmacokinetic properties, 
      whether methadone dosage adjustments are needed on initiation of treatment with 
      pegIFN alfa-2b for HCV in methadone-maintained HIV-positive patients. METHODS: 
      This prospective, nonrandomized, crossover study was conducted at the Albert 
      Einstein College of Medicine and Montefiore Medical Center (Bronx, New York). 
      Patients who were aged > or =18 years, coinfected with chronic HCV and HIV, and 
      had been receiving methadone maintenance treatment (dosage, 40-200 mg/d PO) for 
      at least 8 weeks prior to enrollment were eligible. We determined mean methadone 
      C(max), T(max), Cn,in, AUC, and oral clearance (CL/F) values over a 24-hour 
      period before (baseline) and after the administration of pegIFN alfa-2b 1.5 
      microg/kg SC (2 doses given 1 week apart). To determine differences in opiate 
      withdrawal symptoms, one of the primary investigators administered the Subjective 
      Opiate Withdrawal Scale (SOWS) and Objective Opiate Withdrawal Scale (OOWS) at 
      baseline and 7, 14, and 21 days after the administration of the first dose. Study 
      participants underwent weekly clinical evaluation for signs and symptoms of 
      methadone withdrawal and for AEs of pegIFN. RESULTS: Nine patients were included 
      in the study (7 men, 2 women; 7 Hispanic, 2 black; mean [SD] age, 41 [8.3] years; 
      mean [SD] weight, 75.0 [12.3] kg). We did not observe any significant changes 
      from baseline in mean C(max), T(max), C(min), AUC, and CL/F values despite 80% 
      power to detect a 30% change in either direction. Changes from baseline in SOWS 
      and OOWS scores were not statistically significant. The only AEs reported were 
      mild and consistent with those expected after pegIFN alfa-2b administration, such 
      as inflammation at the injection site and mild, brief, flu-like symptoms. 
      CONCLUSION: Based on the results of this small, prospective, nonrandomized study, 
      pegIFN alfa-2b did not appear to precipitate opioid withdrawal in this sample of 
      methadone-maintained persons with HIV and chronic HCV coinfection; methadone 
      dosage adjustments were unlikely to be needed.
FAU - Berk, Steven I
AU  - Berk SI
AD  - Division of General Internal Medicine, Department of Medicine, Albert Einstein 
      College of Medicine and Montefiore Medical Center, Bronx, New York 10461, USA. 
      sberk@montefiore.org
FAU - Litwin, Alain H
AU  - Litwin AH
FAU - Arnsten, Julia H
AU  - Arnsten JH
FAU - Du, Evelyn
AU  - Du E
FAU - Soloway, Irene
AU  - Soloway I
FAU - Gourevitch, Marc N
AU  - Gourevitch MN
LA  - eng
GR  - M01-RR12248/RR/NCRR NIH HHS/United States
GR  - P30-A1051519/PHS HHS/United States
PT  - Clinical Trial
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Clin Ther
JT  - Clinical therapeutics
JID - 7706726
RN  - 0 (Analgesics, Opioid)
RN  - 0 (Antiviral Agents)
RN  - 0 (Interferon alpha-2)
RN  - 0 (Interferon-alpha)
RN  - 0 (Recombinant Proteins)
RN  - 3WJQ0SDW1A (Polyethylene Glycols)
RN  - G8RGG88B68 (peginterferon alfa-2b)
RN  - UC6VBE7V1Z (Methadone)
SB  - IM
MH  - Administration, Oral
MH  - Adult
MH  - Analgesics, Opioid/administration & dosage/*pharmacokinetics/pharmacology
MH  - Antiviral Agents/adverse effects/*pharmacology
MH  - Area Under Curve
MH  - Cross-Over Studies
MH  - Drug Interactions
MH  - Female
MH  - HIV Infections/complications/drug therapy
MH  - Hepatitis C, Chronic/complications/drug therapy
MH  - Humans
MH  - Injections, Subcutaneous
MH  - Interferon alpha-2
MH  - Interferon-alpha/adverse effects/*pharmacology
MH  - Male
MH  - Methadone/administration & dosage/*pharmacokinetics/pharmacology
MH  - Middle Aged
MH  - Polyethylene Glycols
MH  - Prospective Studies
MH  - Recombinant Proteins
MH  - *Substance Withdrawal Syndrome
EDAT- 2007/03/24 09:00
MHDA- 2007/08/08 09:00
CRDT- 2007/03/24 09:00
PHST- 2006/12/01 00:00 [accepted]
PHST- 2007/03/24 09:00 [pubmed]
PHST- 2007/08/08 09:00 [medline]
PHST- 2007/03/24 09:00 [entrez]
AID - S0149-2918(07)00023-9 [pii]
AID - 10.1016/j.clinthera.2007.01.009 [doi]
PST - ppublish
SO  - Clin Ther. 2007 Jan;29(1):131-8. doi: 10.1016/j.clinthera.2007.01.009.