Relative potency of levo-alpha-acetylmethadol and methadone in humans under acute dosing conditions.
levo-alpha-Acetylmethadol (LAAM) and methadone are full mu-opioid agonists used to treat opioid dependence. Current labeling indicates that LAAM is less potent than methadone. Clinical studies have not determined the relative potency of these drugs. This study compared the effects of acute doses of LAAM and methadone and also examined the ability of naloxone to reverse their effects. Five occasional opioid users received once weekly doses of either placebo, LAAM, or methadone (15, 30, or 60 mg/70 kg p.o.) in agonist exposure sessions and then received naloxone (1.0 mg/70 kg i.m.) 24, 72, and 144 h after agonist exposure. Subject-rated, observer-rated, and physiological measures were assessed regularly. Comparisons of physiological and subjective measures collected in agonist exposure sessions indicate that LAAM is not less potent than methadone under acute dosing conditions. For some measures, LAAM was significantly more potent. Three subjects who entered the study were withdrawn for safety reasons due to greater than anticipated and clinically relevant respiratory depression after receiving 60 mg of LAAM. Naloxone did not fully reverse the pupil constriction produced by 60 mg of LAAM. Acute agonist effects suggest that LAAM may be more potent than methadone and more potent than current labeling indicates. An accurate LAAM:methadone relative potency estimate will aid determination of adequate doses for opioid-dependent patients inducted onto LAAM and for methadone maintenance patients who choose to switch to more convenient thrice-weekly LAAM.
Eissenberg
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Behavioral Pharmacology Research Unit, Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. teissenb@vcu.edu
Stitzer
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Bigelow
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Buchhalter
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Walsh
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D000328:Adult; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000523:psychology; D004305:Dose-Response Relationship, Drug; D006556:Heroin Dependence / Q000523:psychology; D006801:Humans; D008297:Male; D008691:Methadone / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D008692:Methadyl Acetate / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D011680:Pupil / Q000187:drug effects; D017450:Receptors, Opioid, mu / Q000819:agonists*; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology / Q000523:psychology; D011795:Surveys and Questionnaires; D013997:Time Factors
D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D017450:Receptors, Opioid, mu; D009270:Naloxone; D008692:Methadyl Acetate; D008691:Methadone