| The effects of phytoestrogenic isoflavones on the formation and disposition of paracetamol sulfate in the isolated perfused rat liver. | |
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MedLine Citation:
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PMID: 12831506 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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This study examines the potential for the phytoestrogenic isoflavones, a type of complementary medicine, to be involved in pharmacokinetic interactions in the liver. Rat livers were isolated and perfused to steady state, in single-pass mode, with either 5 microM paracetamol (n = 6), or 5 microM paracetamol with a 50:50 molar mixture of genistein and biochanin A or daidzein and formononetin, at a total isoflavone concentration of 1 and 10 microM (n = 6 for each mixture at each concentration). At 1 microM, neither isoflavone mixture had any effect, while at 10 microM both mixtures decreased the clearance of paracetamol and the formation clearance to paracetamol sulfate. Genistein and biochanin A (10 microM) also increased the biliary extraction of hepatically-generated paracetamol sulfate. Additional livers were perfused with an infusion of 5 microM (14)C-paracetamol in the absence (n = 4), or presence, of a 10 microM genistein and biochanin A mixture (n = 4). Analysis of washout perfusate and bile samples (up to 30 min after stopping the infusion) revealed that the isoflavones reduced the first-order rate constant for paracetamol sulfate transport into perfusate, but not for transport into bile. The results indicate that isoflavones can reduce the formation of paracetamol sulfate and that its enhanced excretion into bile arises from the inhibition of sinusoidal efflux transport. |
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Authors:
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Anthony N Lucas; Roger L Nation; Robert W Milne; Geoffrey D Reynolds; Allan M Evans |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The Journal of pharmacy and pharmacology Volume: 55 ISSN: 0022-3573 ISO Abbreviation: J. Pharm. Pharmacol. Publication Date: 2003 May |
Date Detail:
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Created Date: 2003-06-30 Completed Date: 2003-08-12 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0376363 Medline TA: J Pharm Pharmacol Country: England |
Other Details:
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Languages: eng Pagination: 639-46 Citation Subset: IM |
Affiliation:
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Centre for Pharmaceutical Research, School of Pharmaceutical, Molecular and Biomedical Sciences, University of South Australia, S.A. 5000, Australia. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Acetaminophen
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analogs & derivatives*,
metabolism* Animals Estrogens, Non-Steroidal / pharmacokinetics*, pharmacology Isoflavones / pharmacokinetics*, pharmacology Liver / drug effects, metabolism* Male Perfusion / methods Phytoestrogens Plant Preparations Rats Rats, Sprague-Dawley |
| Chemical | |
Reg. No./Substance:
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0/Estrogens, Non-Steroidal; 0/Isoflavones; 0/Phytoestrogens; 0/Plant Preparations; 10066-90-7/acetaminophen sulfate ester; 103-90-2/Acetaminophen |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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