Abstract

1-alpha-acetylmethadol (LAAM) is a long-acting drug similar to methadone. LAAM has been used to help patients discontinue the use of illegal opiates such as heroin. The body converts LAAM to a metabolic product, designated norLAAM, that is then further converted to dinorLAAM. Both norLAAM and dinorLAAM have greater pharmacologic effects than the parent compound, LAAM. A specific enzyme in the liver called cytochrome P450 3A4 is responsible for both of these conversions. P450 3A4 interacts with a number of drugs that are frequently used in clinical medicine. Ketoconazole, a drug widely used to treat fungal infections, is an example of an agent that inhibits the metabolism of many drugs that are converted by P450 3A4. This study was designed to test the hypothesis that ketoconazole would inhibit the conversion of LAAM, and that LAAM, therefore, would not act as potently. To test this hypothesis, volunteer subjects were given LAAM in one experimental session and then, in a separate session, given LAAM plus ketoconazole. Measurements of conversion of LAAM to its metabolites and measurements of its opiate-like effect were made.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
General Clinical Research Centers Program (M01)
Project #
5M01RR000064-36
Application #
6304897
Study Section
Project Start
1999-12-01
Project End
2001-02-28
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
36
Fiscal Year
2000
Total Cost
$1,624
Indirect Cost

  Institution

Name
University of Utah
Department
Type
DUNS #
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112

  Publications

Askie, Lisa M; Darlow, Brian A; Finer, Neil et al. (2018) Association Between Oxygen Saturation Targeting and Death or Disability in Extremely Preterm Infants in the Neonatal Oxygenation Prospective Meta-analysis Collaboration. JAMA 319:2190-2201
Di Fiore, Juliann M; Martin, Richard J; Li, Hong et al. (2017) Patterns of Oxygenation, Mortality, and Growth Status in the Surfactant Positive Pressure and Oxygen Trial Cohort. J Pediatr 186:49-56.e1
Adams, Ted D; Davidson, Lance E; Litwin, Sheldon E et al. (2017) Weight and Metabolic Outcomes 12 Years after Gastric Bypass. N Engl J Med 377:1143-1155
Younge, Noelle; Goldstein, Ricki F; Bann, Carla M et al. (2017) Survival and Neurodevelopmental Outcomes among Periviable Infants. N Engl J Med 376:617-628
Archer, Stephanie Wilson; Carlo, Waldemar A; Truog, William E et al. (2016) Improving publication rates in a collaborative clinical trials research network. Semin Perinatol 40:410-417
Phelps, Dale L; Ward, Robert M; Williams, Rick L et al. (2016) Safety and pharmacokinetics of multiple dose myo-inositol in preterm infants. Pediatr Res 80:209-17
Harper, Lorie M; Mele, Lisa; Landon, Mark B et al. (2016) Carpenter-Coustan Compared With National Diabetes Data Group Criteria for Diagnosing Gestational Diabetes. Obstet Gynecol 127:893-8
Bowles, Neil E; Jou, Chuanchau J; Arrington, Cammon B et al. (2015) Exome analysis of a family with Wolff-Parkinson-White syndrome identifies a novel disease locus. Am J Med Genet A 167A:2975-84
Priester, Tiffany; Ault, Travis G; Davidson, Lance et al. (2015) Coronary calcium scores 6 years after bariatric surgery. Obes Surg 25:90-6
Adams, T D; Hammoud, A O; Davidson, L E et al. (2015) Maternal and neonatal outcomes for pregnancies before and after gastric bypass surgery. Int J Obes (Lond) 39:686-94

Showing the most recent 10 out of 535 publications