Effect of Phenobarbital on Hepatic Transport and Excretion of 131I-Rose Bengal in Children with Cholestasis View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

1972-02

AUTHORS

M Michael Thaler

ABSTRACT

Extract: The effects of phenobarbital (PB) on plasma clearance, hepatic uptake and storage, and excretion in stool and urine of 131I-rose bengal (RB) were studied in seven subjects, six with a variety of hepatobiliary disorders characterized by cholestasis, and one with normal hepatic functions. In three children with patent extrahepatic biliary passages but different degrees and types of cholestasis, plasma t1/2 for RB was shortened from 61.3 to 44.5 hr, from 44.5 to 24.8 hr, and from 155.5 to 96.9 hr before and during PB administration (10 mg/kg/day), respectively. The corresponding quantitative 72-hr fecal excretion of RB increased from 3.2% to 9.2%, from 9.9% to 71.0%, and from 0.3% to 10.0% of the injected dose; the normal subject excreted 78.6% before and 94.9% during PB treatment. Plasma t1/2 and fecal excretion of RB were unchanged in three infants with absence of extrahepatic bile ducts who were treated with PB. Hepatic uptake and storage capacity for RB and renal excretion of RB were not affected by PB.The serum bilirubin concentration (total and direct-reacting) was lowered in patients with cholestatic jaundice not caused by biliary atresia. Interruption of drug therapy was followed by increase in the serum bilirubin to pretreatment concentrations in these patients. Phenobarbital treatment increased reduced nicotinamide adenine dinucleotide phosphate (NADPH)-cytochrome G reductase activity 30–150% in four subjects, whereas activity remained unchanged in three others. The effect of PB on microsomal reductase activity was unrelated to its ability to stimulate hepatic excretion.Phenobarbital in therapeutic dosages enhances biliary excretion of RB and conjugated bilirubin by stimulating hepatic excretory function in patients with intact extrahepatic bile ducts. Hepatic uptake, storage capacity, and NADPH-cytochrome C reductase induction do not seem to be directly involved in the acceleration of hepatic transport.Speculation: Knowledge of the kinetics of 131I-RB distribution in human plasma, tissue, and excreta can serve as a basis for further studies of normal and hepatic excretory functions in man. Phenobarbital-stimulated biliary excretion of anions such as RB and conjugated bilirubin reflects patency of extrahepatic bile ducts. For this reason, PB in conjuction with 131I-RB may prove to be useful agents in the diagnosis and management of various cholestatic conditions. More... »

PAGES

100-110

References to SciGraph publications

  • 1965-01. Beschleunigung der Elimination von Bromsulfthalein (B.S.P.) durch Phenobarbital in NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1203/00006450-197202000-00003

    DOI

    http://dx.doi.org/10.1203/00006450-197202000-00003

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1039865154

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/4403062


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