INTRAVENOUS AND ORAL I-ALPHA-ACETYLMETHADOL - PHARMACODYNAMICS AND PHARMACOKINETICS IN HUMANS

Levo-alpha-acetylmethadol (LAAM) is a long-acting opioid agonist appro ved for use as a maintenance treatment for opioid dependence. Previous clinical studies report that the onset of the effects of LAAM is slow er after parenteral administration than oral administration; however, preclinical studies suggest otherwise. This study examined the pharmac odynamic and pharmacokinetic profile of LAAM when given orally and int ravenously to humans. Opioid-experienced volunteers (n = 6), who were not physically dependent on opioids, received LAAM (20 and 40 mg/70 kg i.v. and p.o.) and placebo under double-blind, double-dummy condition s during five weekly experimental sessions. Behavioral, physiological, subjective and pharmacokinetic measures were collected before and for 96 hr after drug administration. Intravenous LAAM produced significan t subjective and physiological effects that appeared within 5 min, whe reas the effects of oral LAAM appeared more slowly within 1 to 2 hr af ter drug administration. Pharmacokinetic data indicate that the immedi ate effects of intravenous LAAM are largely attributable to the parent drug rather than the active metabolites, nor-LAAM and dinor-LAAM. LAA M produced prototypic opioid agonist effects (i.e., miosis, subjective ratings of high, nodding) that were of equal magnitude across routes, dose-related and of long duration (up to 60 hr). These data are in co ntrast to previous clinical reports and indicate that LAAM produces ef fects of immediate onset when administered parenterally, which suggest s that intravenous LAAM possesses greater abuse potential than previou sly believed.