The Biliary Excretion and Enterohepatic Circulation of Drugs and Other Organic Compounds

Smith, Robert L.

doi:10.1007/978-3-0348-4021-7_5

Cited by 29 publications

(24 citation statements)

References 150 publications

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“…In the rabbit, the pH value of the stomach contents is normally sufficiently low to be bacteriostatic and sometimes low enough to be bactericidal (Smith, 1965). In guinea-pigs that have been actively feeding, the pH of the stomach contents (mean 3-5) is high enough to allow the growth of lactobacilli and bifidobacteria (the organisms least affected by acid conditions), but rats and mice secrete much less gastric acid, so that the ingested flora is not destroyed and there is considerable evidence for multiplication of bacteria in the mouse stomach (Dubos et al, 1965).…”

Section: Clostridiamentioning

confidence: 99%

“…Although the detailed composition is dependent on the nature of the diet (see, for example, Hill et al, 1971), in all cases studied the predominant faecal bacteria are those of the non-sporing strictly anaerobic groups. The metabolic significance of the gut flora is only slowly emerging, but a number of review articles (e.g., Smith, 1966;Scheline, 1968) attribute to it a wide range of reactions of toxicological interest.The involvement of intestinal bacteria in such reactions is usually inferred from indirect evidence-for example, the effect of antibiotic treatment on the metabolism of the drug, or the comparison of germ-free and conventional animals-and there are few direct studies using pure strains of bacteria. In particular, the metabolic activities of the non-sporing strictly anaerobic bacteria are virtually unknown.…”

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confidence: 99%

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confidence: 99%

“…For example, the /%glucosidase responsible for the hydrolysis of aesculin and salicin is also responsible for releasing the active agents from some cardiac glycosides (Lauterbach and Repke, 1960), from cascara sagrada (Fingl, 1965) and from cycasin (Spatz, McDaniel and Laqueur, 1966).…”

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Intestinal Bacteria And The Hydrolysis Of Glycosidic Bonds

Hawksworth

Drašar

Hill

1971

Journal of Medical Microbiology

308

126

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WITH the development of effective anaerobic techniques, the composition of the human intestinal bacterial flora is now more clearly understood. Although the detailed composition is dependent on the nature of the diet (see, for example, Hill et al., 1971), in all cases studied the predominant faecal bacteria are those of the non-sporing strictly anaerobic groups. The metabolic significance of the gut flora is only slowly emerging, but a number of review articles (e.g., Smith, 1966;Scheline, 1968) attribute to it a wide range of reactions of toxicological interest.The involvement of intestinal bacteria in such reactions is usually inferred from indirect evidence-for example, the effect of antibiotic treatment on the metabolism of the drug, or the comparison of germ-free and conventional animals-and there are few direct studies using pure strains of bacteria. In particular, the metabolic activities of the non-sporing strictly anaerobic bacteria are virtually unknown.Many of the enzymes concerned in the metabolism of food additives and drugs are already well known to bacteriologists. For example, the /%glucosidase responsible for the hydrolysis of aesculin and salicin is also responsible for releasing the active agents from some cardiac glycosides (Lauterbach and Repke, 1960), from cascara sagrada (Fingl, 1965) and from cycasin (Spatz, McDaniel and Laqueur, 1966).In the process of detoxification, many compounds are conjugated by the liver to form, for example, glucuronides, and then excreted in the bile into the intestine (Smith, 1966). The glucuronides may then be hydrolysed either by enzymes of the gut mucosa or by enzymes of any bacteria present in the gut, releasing the aglycone, which may be reabsorbed and may be subsequently re-excreted by the liver into the gut.Escherichia coli is well known to produce a /3-glucuronidase (Buehler, Katzman and Doisy, 1951), but E. coli normally constitutes only a small proportion of the gut flora and there are no quantitative studies on the relative contributions to the glucuronidase activity of the gut contents by various bacteria. Similarly the contributions of the different bacterial species to the total activity of other glycosidases in the gut have not been assessed.We have therefore examined the gut flora of four laboratory animals commonly used in toxicological studies and estimated the activity of the glycosidases produced by the principal groups of intestinal bacteria. MATERIALS AND METHODSCharacterisation of the gut flora. All the animals examined were fed ad libitum-rats and mice on diet 41B (Oxoid), rabbits and guinea-pigs on diet SG1. The rats, mice and guineapigs were killed with chloroform and the rabbits by intravenous injection of air. Immediately (1971) 451Downloaded from www.microbiologyresearch.org by after death the abdomen was opened and the gastro-intestinal tract was ligatured at the oesophagus, at the duodenum at a point close to the stomach, at various points along the small intestine, at the ileo-caecal junction and at the rectum. After removal of t...

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Section: Clostridiamentioning

confidence: 99%

mentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Intestinal Bacteria And The Hydrolysis Of Glycosidic Bonds

Hawksworth

Drašar

Hill

1971

Journal of Medical Microbiology

308

126

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“…Pretreatment of the animals with the antibiotic, ampicillin, prior anaesthesia with ether Smith, 1966;Scheline, 1968). One of the most important of these enzymes, from the point of view of conjugate-hydrolysis in the gut, is,-glucuronidase.…”

Section: Discussionmentioning

confidence: 99%

EFFECT OF ETHER ANAESTHESIA ON PHARMACOKINETICS OF N‐(2 HYDROXY ETHYL) 2‐PHENYL ETHYL CARBAMATE: INHIBITION OF ITS ENTEROHEPATIC CIRCULATION

Obianwu

1974

British J Pharmacology

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1The effect of the ether anaesthesia on the plasma half-life of N-(2 hydroxy ethyl) 2-phenyl ethyl carbamate has been studied in rats. 2 The plasma half-life of the carbamate was considerably shorter in animals anaesthetized with ether prior to drug administration than in control rats. 3 The longer plasma half-life of the carbamate in control animals was shown to be due to enterohepatic circulation. 4 Inhibition of this phenomenon by ether was responsible for the shorter plasma half-life of the carbamate in animals anaesthetized with this agent before drug administration. 5 The possible mechanisms by which the ether-induced effect is brought about are discussed.

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Nuclear Receptor Control of Enterohepatic Circulation

Gonzalez¹

2012

Comprehensive Physiology

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Enterohepatic circulation is responsible for the capture of bile acids and other steroids produced or metabolized in the liver and secreted to the intestine, for reabsorption back into the circulation and transport back to the liver. Bile acids are secreted from the liver in the form of mixed micelles that also contain phosphatidylcholines and cholesterol that facilitate the uptake of fats and vitamins from the diet due to the surfactant properties of bile acids and lipids. Bile acids are synthesized in the liver from cholesterol by a cascade of enzymes that carry out oxidation and conjugation reactions, and transported to the bile duct and gall bladder where they are stored before being released into the intestine. Bile flow from the gall bladder to the small intestine is triggered by food intake in accordance with its role in lipid and vitamin absorption from the diet. Bile acids are further metabolized by gut bacteria and are transported back to the circulation. Metabolites produced in the liver are termed primary bile acids or primary conjugated bile salts, while the metabolites generated by bacterial are called secondary bile acids. About 95% of bile acids are reabsorbed in the proximal and distal ileum into the hepatic portal vein and then into the liver sinusoids, where they are efficiently transported into the liver with little remaining in circulation. Each bile acid is reabsorbed about 20 times on average before being eliminated. Enterohepatic circulation is under tight regulation by nuclear receptor signaling, notably by the farnesoid X receptor (FXR).

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The Biliary Excretion and Enterohepatic Circulation of Drugs and Other Organic Compounds

Cited by 29 publications

References 150 publications

Intestinal Bacteria And The Hydrolysis Of Glycosidic Bonds

Intestinal Bacteria And The Hydrolysis Of Glycosidic Bonds

EFFECT OF ETHER ANAESTHESIA ON PHARMACOKINETICS OF N‐(2 HYDROXY ETHYL) 2‐PHENYL ETHYL CARBAMATE: INHIBITION OF ITS ENTEROHEPATIC CIRCULATION

Nuclear Receptor Control of Enterohepatic Circulation

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