title: Inhibition of haloperidol reduction by non-steroidal anti-inflammatory drugs in human liver cytosol.
abstract: A thorough knowledge of drug-drug interactions is crucial as the practice of multiple drug therapy escalates. In vitro studies using human liver enzymes are a valuable and non-invasive tool for predicting potential drug interactions in vivo. 1. A simple radio-TLC method was developed to monitor the formation of reduced haloperidol from haloperidol in human liver cytosol. 2. Indomethacin, known to be a potent inhibitor of 3a-hydroxysteroid dehydrogenase, was chosen as a reference for the evaluation of several arylpropionic acid derived non-steroidal anti-inflammatory drugs, ketoprofen, tiaprofenic acid, fenbufen, Ibuprofen, d-naproxen and 1-naproxen. The IC₅₀ ranged from 0.4-6.0 mM with indomethacin the most potent inhibitor of haloperidol carbonyl reductase. 3. The carbonyl reduction of haloperidol was inhibited significantly by these most commonly used non-steroidal anti-inflammatory drugs and the degree of inhibition reflected their pharmacological potency. 4. Sephadex G-100 fractionation of human liver cytosol yielded a fraction with haloperidol reductase activity at a molecular weight of about 32,000.
authors.forename: S
authors.initials: S
authors.lastname: Fayz
authors.forename: T
authors.initials: T
authors.lastname: Inaba
mesh_terms: D000429:Alcohol Oxidoreductases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006220:Haloperidol / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D010084:Oxidation-Reduction / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000429:Alcohol Oxidoreductases; C063466:haloperidol reductase; D006220:Haloperidol