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.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
General Clinical Research Centers Program (M01)
Project #
3M01RR000064-36S1
Application #
6419493
Study Section
Project Start
1999-12-01
Project End
2001-02-28
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
36
Fiscal Year
2001
Total Cost
$248,088
Indirect Cost
Name
University of Utah
Department
Type
DUNS #
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112
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