Sl. Walsh et al., INTRAVENOUS AND ORAL I-ALPHA-ACETYLMETHADOL - PHARMACODYNAMICS AND PHARMACOKINETICS IN HUMANS, The Journal of pharmacology and experimental therapeutics, 285(1), 1998, pp. 71-82
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.