| Disposition of nifurtimox and metabolite activity against Trypanosoma cruzi using rat isolated perfused liver. | |
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MedLine Citation:
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PMID: 8083806 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Nifurtimox disposition was investigated using the rat isolated perfused-liver method after administration of 25 micrograms mL-1 nifurtimox, and its disappearance was monitored by analysing the perfusate sample at various times. Biliary excretion was also measured. The drug concentration profile underwent a biexponential decline over the 2-h study period, with a terminal half-life of 62.76 +/- 17.56 min. Nifurtimox is a high clearance compound (15.23 +/- 5.53 mL min-1). The extraction ratio was 0.621 +/- 0.159. Biliary excretion accounted for 0.05% of the dose, the remainder consisting of highly polar metabolites. By 2 h, a minimal fraction of unchanged nifurtimox was recovered from the perfusate. Nifurtimox activity against Trypanosoma cruzi (clone CA-1) during the perfusion was also determined. Epimastigotes isolated from continuous culture were exposed to the samples of perfusate at different perfusion times in a microtitre plate. After an incubation time of 72 h at 27 degrees C, the parasite number in each well was counted under a microscope. From 0 to 75 min after the perfusion, the anti-trypanosomal activity decreased, but an increase in activity was observed at the later times. These findings show that active metabolites are formed during the perfusion. |
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Authors:
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G González-Martin; C Paulos; A Guevara; G Ponce |
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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: 46 ISSN: 0022-3573 ISO Abbreviation: J. Pharm. Pharmacol. Publication Date: 1994 May |
Date Detail:
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Created Date: 1994-10-13 Completed Date: 1994-10-13 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: 356-9 Citation Subset: IM |
Affiliation:
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Department of Pharmacy, Faculty of Chemistry, Pontifical Catholic University of Chile, Santiago. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Bile / metabolism Half-Life Humans Liver / drug effects, metabolism* Male Nifurtimox / pharmacokinetics*, pharmacology Perfusion Rats Rats, Sprague-Dawley Trypanosoma cruzi / drug effects* |
| Chemical | |
Reg. No./Substance:
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23256-30-6/Nifurtimox |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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