TY - JOUR
T1 - Effects of pegylated interferon alfa-2b on the pharmacokinetic and pharmacodynamic properties of methadone
T2 - A prospective, nonrandomized, crossover study in patients coinfected with hepatitis c and hiv receiving methadone maintenance treatment
AU - Berk, Steven I.
AU - Litwin, Alain H.
AU - Arnsten, Julia H.
AU - Du, Evelyn
AU - Soloway, Irene
AU - Gourevitch, Marc N.
N1 - Funding Information:
This research was supported by the Center for AIDS Research at AECOM and Montefiore Medical Center (grant no. NIH P30-A1051519), and in part by a GCRC grant (no. NIH M01-RR12248) awarded to the AECOM of Yeshiva University, Bronx, New York. Dr. Litwin and Ms. Soloway have been members of the speakers' bureau at Schering-Plough Corporation, Kenilworth, New Jersey. Drs. Litwin and Gourevitch have received financial support for research from Schering-Plough Corporation.
PY - 2007/1
Y1 - 2007/1
N2 - 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 ≥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 Cmax, Tmax, 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 μg/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 Cmax, Tmax, Cmin, 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, flulike 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.
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 ≥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 Cmax, Tmax, 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 μg/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 Cmax, Tmax, Cmin, 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, flulike 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.
KW - HIV
KW - hepatitis C
KW - methadone
KW - pegylated interferon
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U2 - 10.1016/j.clinthera.2007.01.009
DO - 10.1016/j.clinthera.2007.01.009
M3 - Article
C2 - 17379053
AN - SCOPUS:33947257773
SN - 0149-2918
VL - 29
SP - 131
EP - 138
JO - Clinical Therapeutics
JF - Clinical Therapeutics
IS - 1
ER -
