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In vitro metabolism of amiodarone by rabbit and rat liver and small intestine.
Drug Metab Dispos. 1986 Jul-Aug; 14(4):423-9.DM

Abstract

The present studies were designed to investigate whether amiodarone (Am) is metabolized in the major organs and tissues of the rat and rabbit. Incubations using Am and tissue homogenates (600 g supernatant) of rabbit and rat lung, liver, kidney, and gut revealed formation of desethylamiodarone (DEA) by the liver and gut. Subsequent experiments using the post-mitochondrial, cytosolic, and microsomal fractions of these tissues indicated that metabolism of Am was greatest in the microsomal fractions. In both species, greater DEA formation was detected for microsomes of hepatic origin. The hepatic microsomal mediated production of DEA was altered by protein concentration in both the rabbit and rat preparations with protein concentrations of 5 mg providing the greatest DEA production. DEA formation by gut microsomes was greatest at 3 mg of protein for the rabbit but exhibited no significant change from 1 mg to 10 mg of protein for the rat. In vitro metabolism of Am by rabbit and rat hepatic microsomal preparations was significantly reduced by 1 mM piperonyl butoxide, SKF 525-A, n-octylamine, and carbon monoxide. Effects of these inhibitors on rabbit and rat gut microsomal incubations were inconclusive. HPLC analysis of incubation samples revealed a species difference in the metabolism of Am as demonstrated by the detection of three metabolites in addition to DEA. The unidentified metabolites (I, II, III) were detected in rabbit hepatic microsomal incubations. Metabolite II was also detected in incubations using rabbit duodenal tissue microsomes. No metabolites other than DEA were found in incubations using rat tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

Authors

No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

2873989

Citation

Young, R A., and H M. Mehendale. "In Vitro Metabolism of Amiodarone By Rabbit and Rat Liver and Small Intestine." Drug Metabolism and Disposition: the Biological Fate of Chemicals, vol. 14, no. 4, 1986, pp. 423-9.
Young RA, Mehendale HM. In vitro metabolism of amiodarone by rabbit and rat liver and small intestine. Drug Metab Dispos. 1986;14(4):423-9.
Young, R. A., & Mehendale, H. M. (1986). In vitro metabolism of amiodarone by rabbit and rat liver and small intestine. Drug Metabolism and Disposition: the Biological Fate of Chemicals, 14(4), 423-9.
Young RA, Mehendale HM. In Vitro Metabolism of Amiodarone By Rabbit and Rat Liver and Small Intestine. Drug Metab Dispos. 1986 Jul-Aug;14(4):423-9. PubMed PMID: 2873989.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - In vitro metabolism of amiodarone by rabbit and rat liver and small intestine. AU - Young,R A, AU - Mehendale,H M, PY - 1986/7/1/pubmed PY - 1986/7/1/medline PY - 1986/7/1/entrez SP - 423 EP - 9 JF - Drug metabolism and disposition: the biological fate of chemicals JO - Drug Metab Dispos VL - 14 IS - 4 N2 - The present studies were designed to investigate whether amiodarone (Am) is metabolized in the major organs and tissues of the rat and rabbit. Incubations using Am and tissue homogenates (600 g supernatant) of rabbit and rat lung, liver, kidney, and gut revealed formation of desethylamiodarone (DEA) by the liver and gut. Subsequent experiments using the post-mitochondrial, cytosolic, and microsomal fractions of these tissues indicated that metabolism of Am was greatest in the microsomal fractions. In both species, greater DEA formation was detected for microsomes of hepatic origin. The hepatic microsomal mediated production of DEA was altered by protein concentration in both the rabbit and rat preparations with protein concentrations of 5 mg providing the greatest DEA production. DEA formation by gut microsomes was greatest at 3 mg of protein for the rabbit but exhibited no significant change from 1 mg to 10 mg of protein for the rat. In vitro metabolism of Am by rabbit and rat hepatic microsomal preparations was significantly reduced by 1 mM piperonyl butoxide, SKF 525-A, n-octylamine, and carbon monoxide. Effects of these inhibitors on rabbit and rat gut microsomal incubations were inconclusive. HPLC analysis of incubation samples revealed a species difference in the metabolism of Am as demonstrated by the detection of three metabolites in addition to DEA. The unidentified metabolites (I, II, III) were detected in rabbit hepatic microsomal incubations. Metabolite II was also detected in incubations using rabbit duodenal tissue microsomes. No metabolites other than DEA were found in incubations using rat tissues.(ABSTRACT TRUNCATED AT 250 WORDS) SN - 0090-9556 UR - https://www.unboundmedicine.com/medline/citation/2873989/In_vitro_metabolism_of_amiodarone_by_rabbit_and_rat_liver_and_small_intestine_ DB - PRIME DP - Unbound Medicine ER -