Methadone is an effective
therapy for
heroin addiction, but the public health benefits are compromised by diversion and injection of prescribed
methadone. Combination with
naloxone is one way to reduce the risk of diversion and injection. Two studies were conducted. The first ascertained the safety, tolerability, pharmacokinetics, and pharmacodynamics of oral
methadone-
naloxone in a 50:1 ratio compared with
methadone. The second study investigated the effectiveness of intramuscularly injected
methadone-
naloxone in precipitating withdrawal in
methadone-maintained subjects. The first double-blind, crossover study randomized 10 stable
methadone-maintained subjects equally to receive either
methadone-
naloxone or
methadone over two alternate 14 day periods. In the second study, 5 subjects received
intramuscular injections of
methadone-
naloxone before their scheduled
methadone dose. Oral
methadone-
naloxone in a 50:1 ratio appeared to be well tolerated, although a taste difference between the preparations may have compromised blinding. There were no significant differences between
methadone and
methadone-
naloxone in objective and subjective
opioid withdrawal signs, and trough and peak plasma concentrations.
Methadone-
naloxone in a 50:1 ratio intramuscularly precipitated mild to moderate signs of
opioid withdrawal in 4 out of 5 subjects whereas a 5th subject who did not experience withdrawal at a lower dose refused higher dose challenges.
Withdrawal symptoms peaked 15 to 30 minutes postchallenge and returned to baseline levels at 60 minutes.
Methadone-
naloxone in 50:1 ratio has the pharmacological properties to be a useful combination product for treatment of
heroin addiction with reduced risk of injection.