The primary goal of this project is to study the involvement of a specific cytochrome P450 in the N-demethylation of the anti-abuse medication, 1-(-acetylmethadol (LAAM). Preliminary studies in human liver microzomes suggest that P540 3A4 selectively N-demethylates LAAM. The investigator hypothesizes that inhibition of LAAM metabolism will decrease its pharmacodynamic activity. The hypothesis will be tested in human subjects given a single oral dose of LAAM, with or without ketoconazole. The prediction is that ketoconazole will increase the half-life of LAAM, decrease the production of norLAAM and dinorLAAM and diminish a pharmacodynamic endpoint, pupillary constriction. Twenty subjects (ten men and ten women) have been recruited for this study. The study has just begun, and preliminary results are not yet available.
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