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David E. Moody

Research Professor of Pharmacology and Toxicology

Education and Training

B.A., 1972, University of Kansas, Chemistry

Ph.D., 1977, University of Kansas, Experimental Pathology

Postdoctoral Fellow, 1977-1980, University of Californai San Francisco

Research Interests

Our laboratory is studying the involvement of specific cytochrome P450s (P450 / gene family CYP) in the metabolism of psychoactive drugs. Our laboratory initially focused on animal models of psychoactive drug metabolism. We found that P450 2D1 is responsible for the in vivo ring-hydroxylation of amphetamine in rats. P450 2D exhibits a genetic polymorphism in humans (approximately 8% of humans are poor metabolizers of P450 2D), which suggests this route of amphetamine metabolism may be suppressed in a part of the population. Our efforts have now moved to the use of human liver microsomes and cDNA-expressed human P450s. These systems have been employed to show that P450 3A4 is responsible for the metabolism of two antiabuse agents, l-a-acetylmethadol (LAAM) and methadone. Clinical pharmacokinetic studies are now underway to provide in vitro and in vivo comparative results on isozyme specificity in the human metabolism of LAAM.We are now embarking on similar in vitro experiments with anotherÊ anti-abuse medication, buprenorphine, with this work we will expand into use of hepatocyte cultures and glucuronidation pathways. Pursuit of this research has required development of methods to detect specific P450s and to detect specific drugs and their metabolites.

The above research was carried out with graduate students and postdoctoral fellows in the laboratory. Rotation students have also been encouraged to work on forensic projects or areas that I have past expertise in. The forensic work included characterization of the cross-reactivity of immunoassays for psychoactive drugs. Vestigal research interests lie in the biological response of drug-metabolizing enzymes, specifically epoxide hydrolases, and mechanisms of hepatotoxicity. The epoxide hydrolases are important in the hydrolysis of reactive cyclic ethers, many of which can form adducts with intracellular proteins and DNA. We have recently shown that the induction of microsomal epoxide hydrolase correlates closely with certain phase II drug metabolizing enzymes.

Selected Publications

Law, M.Y.L., Slawson, M.H. and Moody, D.E.  The selective involvement of the cytochrome P450 2D subfamily in the in vivo 4-hydroxylation of amphetamine in the rat.  Drug Metab. Dispos.  28: 348-353, 2000

Neff, J.A. and Moody, D.E.  Differential N-demethylation of l-a-acetylmethadol (LAAM) and norLAAM by cytochrome P450s 2B6, 2C18 and 3A4.  Biochem. Biophys. Res. Commun.  284: 751-756, 2001.

Moody, D.E., Walsh, S.L., Rollins, D.E., Neff, J.A. and Huang, W.  Ketoconazole, a cytochrome P450 3A4 inhibitor, markedly increases concentrations of l-acetyl-a-methadol (LAAM) in opioid-naïve individuals.  Clin. Pharmacol. Ther.  76: 154-166, 2004.

Chang, Y. and Moody, D.E.  Effect of benzodiazepines on the metabolism of buprenorphine in human liver microsomes.  Eur. J. Clin. Pharmacol.  60: 875-881, 2005.

Chang, Y., Moody, D.E. and McCance-Katz, E.F.  Novel metabolites of buprenorphine detected in human liver microsomes and human urine.  Drug Metab. Dispos. 34: 440-448, 2006.

Huang, W., Moody, D.E. and McCance-Katz, E.F.  The in vivo glucuronidation of buprenorphine and norbuprenorphine determined by liquid chromatography-electrospray ionisation-tandem mass spectrometry.  Ther. Drug Monit.  28: 245-251, 2006.

Pharmacology & Toxicology   College of Pharmacy   30 S. 2000 E., Rm 201, SLC  UT 84112  phone: 801-581-6287  fax: 801-585-5111 phtx@pharm.utah.edu