L-alpha-acetylmethadol (LAAM) is currently being investigated as a substitute for methadone in the treatment of narcotic abstinence symptoms. Whereas both drugs are useful as antagonists to heroin addiction, LAAM has a longer duration of pharmacologic activity than methadone. They are cleared by a common metabolic pathway, N-demethylation, and both drugs are very extensively bound to plasma proteins. Therefore, drug-drug interaction is likely to occur when LAAM is administered to patients previously maintained on methadone. In the proposed project, the pharmacokinetics of methadone following acute and repeated intravenous administration to beagel dogs will be studied. Incidence of drug metabolizing enzyme induction or inhibition will be investigated, and the effect of these changes on the distribution and elimination of LAAM and its metabolites will be examined by administering LAAM before and after the repeated methadone doses, and studying the resulting plasma profiles. The extent of binding of LAAM to plasma proteins will be measured in each case, using the equilibrium dialysis technique. HPLC methods will be explored to separate methadone, LAAM and their metabolites extracted from plasma, followed by quantitation of the radioactive isotopes using a liquid scintillation counter. The type of information generated from this study will be useful in the treatment of patients withdrawing from narcotic drugs of abuse.
NIH ExPorter
NIH ExPorter