| Impulse-response studies on tracer doses of [14C]lignocaine and its multiple metabolites in the perfused rat liver. | |
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MedLine Citation:
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PMID: 9364412 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The outflow-concentration-time profiles for lignocaine (lidocaine) and its metabolites have been measured after bolus impulse administration of [14C]lignocaine into the perfused rat liver. Livers from female Sprague-Dawley rats were perfused in a once-through fashion with red-blood-cell-free Krebs-Henseleit buffer containing 0 or 2% bovine serum albumin. Perfusate flow rates of 20 and 30 mL min-1 were used and both normal and retrograde flow directions were employed. Significant amounts of metabolite were detected in the effluent perfusate soon after lignocaine injection. The early appearance of metabolite contributed to bimodal outflow profiles observed for total 14C radioactivity. The lignocaine outflow profiles were well characterized by the two-compartment dispersion model, with efflux rate << influx rate. The profiles for lignocaine metabolites were also characterized in terms of a simplified two-compartment dispersion model. Lignocaine was found to be extensively metabolized under the experimental conditions with the hepatic availability ranging between 0.09 and 0.18. Generally lignocaine and metabolite availability showed no significant change with alterations in perfusate flow rate from 20 to 30 mL min-1 or protein content from 0 to 2%. A significant increase in lignocaine availability occurred when 1200 microM unlabelled lignocaine was added to the perfusate. Solute mean transit times generally decreased with increasing flow rate and with increasing perfusate protein content. The results confirm that lignocaine pharmacokinetics in the liver closely follow the predictions of the wellstirred model. The increase in lignocaine availability when 1200 microM unlabelled lignocaine was added to the perfusate is consistent with saturation of the hydroxylation metabolic pathways of lignocaine metabolism. |
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Authors:
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G D Mellick; M S Roberts |
Publication Detail:
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Type: In Vitro; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The Journal of pharmacy and pharmacology Volume: 49 ISSN: 0022-3573 ISO Abbreviation: J. Pharm. Pharmacol. Publication Date: 1997 Oct |
Date Detail:
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Created Date: 1998-02-11 Completed Date: 1998-02-11 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: 1008-18 Citation Subset: IM |
Affiliation:
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University of Queensland, Department of Medicine, Princess Alexandra Hospital, Australia. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Anesthetics, Local
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pharmacokinetics* Animals Area Under Curve Biological Availability Biotransformation Chromatography, High Pressure Liquid Female Hydroxylation Lidocaine / pharmacokinetics* Liver / metabolism* Models, Biological Rats Rats, Sprague-Dawley |
| Chemical | |
Reg. No./Substance:
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0/Anesthetics, Local; 137-58-6/Lidocaine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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