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Title: Factors influencing the biliary excretion of organic compounds
Author: Hirom, Paul Christopher
Awarding Body: University of London
Current Institution: Imperial College London
Date of Award: 1970
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The factors influencing the biliary excretion of organic compounds are not well understood. However, compounds with a polar anionic group are known to require a minimum molecular weight of 325 ± 50 for marked biliary excretion in the rat. In this study, the influenoe upon biliary excretion of molecular weight, urinary excretion, moleoular structure and physico-chemical properties, species differences and plasma binding has been investigated using a series of 25 sulphonamides of closely related structure. Antonio sulphonamides were excreted predominantly unchanged in both bile and urine, thus avoiding any effects on biliary excretion due to metabolism. In the rat, the minimum molecular weight for marked biliary excretion (325 ±50) applied, but, above this,no close correlation existed between molecular weight and extent of biliary excretion. Urinary excretion influenced the extent of biliary excretion of those compounds which could be excreted by both routes but, in the absence of urinary function, compounds still varied in affinity for biliary excretion. Compounds of amphipathic nature were best suited for biliary excretion whereas those of predominantly hydrophilic nature were excreted in the urine. Compared with the rat, molecules of greater lipophilic character appeared to be necessary for marked biliary excretion in the rabbit and guinea pig. Bile flow rate and bile concentration may also influence species differences. Plasma binding did not appear to be responsible for differences in biliary excretion. The work suggested that hepato-biliary mechanisms of bile formation rather than extra-hepatic factors were responsible for differences in biliary excretion. A study of absorption from the biliary system of a varied group of compounds showed that only hydrophilic molecules. not normally exoreted in the bile. were rapidly absorbed into the bloodstream. Selective reabsorption of compounds after canalicular secretion could, therefore. explain the observed patterns of biliary excretion.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available