| Stereoselective glucuronidation of zileuton isomers by human hepatic microsomes. | |
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MedLine Citation:
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PMID: 7720519 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The glucuronidation of the R-isomer and S-isomer of the 5-lipoxygenase inhibitor zileuton was examined using human hepatic microsomes. The glucuronidation of both isomers followed Michaelis-Menten kinetics, but glucuronidation rates were between 3.6- and 4.3-fold greater for the S-isomer. The apparent Km's (microM) for the R-isomer (392.9 +/- 35.9) and S-isomer (322.5 +/- 22.0) glucuronidation were similar, whereas the apparent Vmax (nmol/mg protein/min) was 3.4-fold greater for the S-isomer (5.2 +/- 0.7). In combination, each isomer competitively inhibited the glucuronidation of its antipode. The average Ki (microM) determined for S-isomer inhibition of R-isomer glucuronidation (197.8 +/- 61.3) was 2.4-fold lower than the Ki for the reciprocal interaction. These data indicate that the glucuronidation of the zileuton isomers in human hepatic microsomes is stereoselective. This stereoselective glucuronidation may be the basis for the more rapid clearance of the S-isomer observed in humans receiving zileuton. |
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Authors:
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D J Sweeny; H N Nellans |
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Publication Detail:
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Type: In Vitro; Journal Article |
Journal Detail:
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Title: Drug metabolism and disposition: the biological fate of chemicals Volume: 23 ISSN: 0090-9556 ISO Abbreviation: Drug Metab. Dispos. Publication Date: 1995 Jan |
Date Detail:
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Created Date: 1995-05-23 Completed Date: 1995-05-23 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 9421550 Medline TA: Drug Metab Dispos Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 149-53 Citation Subset: IM |
Affiliation:
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Department of General Pharmacology, Abbott Laboratories, Abbott Park, IL 60064-3500. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Anti-Inflammatory Agents, Non-Steroidal
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metabolism* Chromatography, High Pressure Liquid Chromosomes, Human / metabolism Glucuronates / metabolism Humans Hydroxyurea / analogs & derivatives*, metabolism Microsomes, Liver / metabolism* Stereoisomerism |
| Chemical | |
Reg. No./Substance:
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0/Anti-Inflammatory Agents, Non-Steroidal; 0/Glucuronates; 127-07-1/Hydroxyurea; 132880-11-6/zileuton |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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