Abstract
1. The biliary excretion of [14C]trimophonium iodide [tri[14C]methyl(3-hydroxyphenyl)ammonium iodide] was studied in normal Wistar animals and in jaundiced homozygous Gunn rats. 2. In normal Wistar rats small amounts of radioactivity (approx. 3% of the dose in 4h) were excreted in bile as two glucuronide conjugates, i.e. [14C]trimophonium glucuronide [tri[14C]methyl-(3-oxyphenyl)ammonium glucuronide] (85%) and 3-di[14C]methylaminophenyl glucuronide (10–15%). Only minor amounts of the unchanged drug were detected in bile. 3. In the homozygous jaundiced Gunn rat large amounts of radioactivity (26% of the dose in 4h) were eliminated in bile as [14C]trimophonium glucuronide alone. The quantitative excretion of this metabolite in Gunn rat bile was about ten times that in normal animals. 4. It is proposed that the biochemical lesion in the homozygous Gunn rat may indirectly affect the biliary transport of exogenous glucuronides across the canalicular membrane.
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Selected References
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- ARIAS I. M., JOHNSON L., WOLFSON S. Biliary excretion of injected conjugated and unconjugated bilirubin by normal and Gunn rats. Am J Physiol. 1961 May;200:1091–1094. doi: 10.1152/ajplegacy.1961.200.5.1091. [DOI] [PubMed] [Google Scholar]
- Clark B. The in vitro inhibition of the N-demethylation of pethidine by phenelzine (Phenethylhydrazine). Biochem Pharmacol. 1967 Dec;16(12):2369–2385. doi: 10.1016/0006-2952(67)90222-5. [DOI] [PubMed] [Google Scholar]
- GAUDETTE L. E., BRODIE B. B. Relationship between the lipid solubility of drugs and their oxidation by liver microsomes. Biochem Pharmacol. 1959 Aug;2:89–96. doi: 10.1016/0006-2952(59)90075-9. [DOI] [PubMed] [Google Scholar]
- Gartner L. M., Arias I. M. Formation, transport, metabolism and excretion of bilirubin. N Engl J Med. 1969 Jun 12;280(24):1339–1345. doi: 10.1056/NEJM196906122802409. [DOI] [PubMed] [Google Scholar]
- LA DU B. N., GAUDETTE L., TROUSOF N., BRODIE B. B. Enzymatic dealkylation of aminopyrine (pyramidon) and other alkylamines. J Biol Chem. 1955 Jun;214(2):741–745. [PubMed] [Google Scholar]
- MAZEL P., HENDERSON J. F. ON THE RELATIONSHIP BETWEEN LIPID SOLUBILITY AND MICROSOMAL METABOLISM OF DRUGS. Biochem Pharmacol. 1965 Jan 1;14:92–94. doi: 10.1016/0006-2952(65)90063-8. [DOI] [PubMed] [Google Scholar]
- SCHANKER L. S. Passage of drugs across body membranes. Pharmacol Rev. 1962 Dec;14:501–530. [PubMed] [Google Scholar]
- SCHANKER L. S., SOLOMON H. M. Active transport of quaternary ammonium compounds into bile. Am J Physiol. 1963 May;204:829–832. doi: 10.1152/ajplegacy.1963.204.5.829. [DOI] [PubMed] [Google Scholar]
- SCHMID R., AXELROD J., HAMMAKER L., SWARM R. L. Congenital jaundice in rats, due to a defect in glucuronide formation. J Clin Invest. 1958 Aug;37(8):1123–1130. doi: 10.1172/JCI103702. [DOI] [PMC free article] [PubMed] [Google Scholar]
- WOODS L. A. Distribution and fate of morphine in non-tolerant and tolerant dogs and rats. J Pharmacol Exp Ther. 1954 Oct;112(2):158–175. [PubMed] [Google Scholar]
