• Pharmacokinetic (PK) and Pharmacodynamic (PD) Evaluation of Methadone (MD) Enantiomers Following Co-Administration with Amprenavir (APV) in Opioid-Dependent Subjects
  Poster 1649
  Authored by C. Hendrix, J. Wakeford, M. B. Wire, G. Bigelow, E. Cornell, J. Christopher, E. Fuchs, J. Snidow

Intravenous drug users (IDUs) continue to account for a significant number of HIV cases in the U.S. Many of these patients, as part of their treatment, are taking antiretroviral therapy (including protease inhibitors) concomitantly with methadone. Methadone is a synthetic narcotic analgesic and is metabolized in the liver by CYP3A4. The same enzymatic complex also metabolizes amprenavir. The possibility of interactions between these two drugs has been suggested, as has been the case with other protease inhibitors. Pharmacokinetic data have shown that the concentration of methadone decreases when methadone is co-administrated with other protease inhibitors known to inhibit the same CYP3A. It is important that the pharmacokinetic interactions of these two drugs are defined so that we can appropriately make decisions regarding potential dose adjustment and avoid untoward reactions with either medication.

The objectives of this study were to determine the steady-state pharmacokinetics of methadone in the presence or absence of amprenavir. Also, they wanted to determine the effect of multiple doses of methadone on the steady state and to evaluate the short-term safety of this combination. The study also looked at any change in the pharmacodynamics effects of both methadone and amprenavir when combined.

This study, conducted by C. Hendrix, enrolled 17 HIV-seronegative subjects currently on a certified methadone maintenance program. Amprenavir was given for 12 days to the 17 subjects. Serial methadone and amprenavir PK levels were collected. Co-administration of amprenavir was associated with a delay in absorption for methadone. This delay did not resulted in any significant symptomatology. The author concluded that a priori adjustment of methadone dose is not required during co-administration with amprenavir. The study design did not allow to assess changes on amprenavir concentrations when co-administered with methadone. Therefore, no specific recommendation on dose change for amprenavir is recommended when co-administrated with methadone.