Human Liver Aldehyde Oxidase: Inhibition by 239 Drugs
- 1 January 2004
- journal article
- review article
- Published by Wiley in The Journal of Clinical Pharmacology
- Vol. 44 (1), 7-19
- https://doi.org/10.1177/0091270003260336
Abstract
The authors tested 239 frequently used drugs and other compounds for their potential to inhibit the drug‐metabolizing enzyme, aldehyde oxidase, in human liver cytosol. A sensitive, moderate throughput HPLC‐MS assay was developed for 1‐phthalazinone, the aldehyde oxidase–catalyzed product of phthalazine oxidation. Inhibition of this activity was examined for the 239 drugs and other compounds of interest at a test concentration of 50 μM. Thirty‐six compounds exhibited greater than 80% inhibition and were further examined for measurement of IC50. The most potent inhibitor observed was the selective estrogen receptor modulator, raloxifene (IC50 = 2.9 nM), and tamoxifen, estradiol, and ethinyl estradiol were also potent inhibitors. Other classes of drugs that demonstrated inhibition of aldehyde oxidase included phenothiazines, tricyclic antidepressants, tricyclic atypical antipsychotic agents, and dihydropyridine calcium channel blockers, along with some other drugs, including loratadine, cyclobenzaprine, amodiaquine, maprotiline, ondansetron, propafenone, domperidone, quinacrine, ketoconazole, verapamil, tacrine, and salmeterol. These findings are discussed in context to potential drug interactions that could be observed between these agents and drugs for which aldehyde oxidase is involved in metabolism and warrant investigation of the possibility of clinical drug interactions mediated by inhibition of this enzyme.This publication has 19 references indexed in Scilit:
- Mammalian molybdo-flavoenzymes, an expanding family of proteins: structure, genetics, regulation, function and pathophysiologyBiochemical Journal, 2003
- Metabolism of zaleplon by human liver: evidence for involvement of aldehyde oxidaseXenobiotica, 2002
- Inhibition of zaleplon metabolism by cimetidine in the human liver:in vitrostudies with subcellular fractions and precision-cut liver slicesXenobiotica, 2002
- Molybdenum HydroxylasesPublished by Wiley ,2001
- Stereoselective Biotransformation of the Selective Serotonin Reuptake Inhibitor Citalopram and Its Demethylated Metabolites by Monoamine Oxidases in Human LiverBiochemical Pharmacology, 1998
- Molecular cloning, refined chromosomal mapping and structural analysis of the human gene encoding aldehyde oxidase (AOX1), a candidate for the ALS2 geneRedox Report, 1997
- Enzymology of the metabolic pathway from nicotine to cotinine,in vitroEuropean Journal of Drug Metabolism and Pharmacokinetics, 1983
- The enzyme “aldehyde oxidase” is an iminium oxidase. Reaction with nicotine Δ1′(5′) iminium ionBiochemical and Biophysical Research Communications, 1979
- Human Liver Aldehyde Oxidase: Differential Inhibition of Oxidation of Charged and Uncharged Substrates*JCI Insight, 1967
- Hepatic Aldehyde OxidaseOnline Journal of Public Health Informatics, 1962