Entero-hepatic Circulation

Once in the gastrointestinal tract, chemicals that have undergone conjugation reactions in the liver may be subject to the action of hydrolytic enzymes that de-conjugate the molecule. De-conjugation results in increased lipophilicity of the molecule and renders them once again subject to passive uptake. Re-absorbed chemicals enter the circulation via the hepatic portal vein, which shunts the chemical back to the liver where 

The liver functions to collect chemicals and other wastes from the body. Accordingly, high levels of chemicals may be attained in the liver, resulting in toxicity to this organ. Biotransformation of chemicals that occur in the liver sometimes results in the generation of reactive compounds that are more toxic than the parent compound resulting in damage to the liver. Chemical toxicity to the liver is discussed elsewhere (Chapter 14). 

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Since animal data indicated the presence of an entero-hepatic circulation [59], the biliary concentration of rifaximin after oral preoperative administration of the drug (400 mg every 12 h) was evaluated in bile samples taken from patients undergoing cholecystectomy [106]. In 7 out... 

The answer is b. (Katzung, p J129.) Ampicillin decreases the entero-hepatic circulation of estrogen, thereby reducing its efficacy It is thought that this occurs because of an alteration in the gastrointestinal flora. Other oral antibiotics may produce a similar effect... 

They are useful only in hyperlipoproteinemias involving elevated levels of LDL i.e. type Ila, lib and V. They are basic ion exchange resins. They are neither digested nor absorbed in the gut. They bind bile acids in intestine and interrupt their entero-hepatic circulation, leading to increased faecal excretion of bile salts and cholesterol. There is increased hepatic conversion of choles-terol to bile acids. More LDL receptors are expressed on liver cells leading to increased clearance of IDL, LDL and indirectly of VLDL. 

Sorafenib pharmacokinetics shows a large interpatient variability [49, 57], The large interpatient variability is supposed to be the result of slow dissolution of the drug in the gastrointestinal tract and of the existence of an entero-hepatic circulation [51],... 

Remie R, Rensema JW, van Wunnik GHJ, van Dongen JJ (1990) Permanent double bile fistula (with intact entero-hepatic circulation). In van Dongen JJ, Remie R, Rensema JW, van Wunnik GHJ (eds) Manual of microsurgery on the laboratory rat. Vol I. Elsevier, Amsterdam, pp 201-212 Remie R, Rensema JW, Havinga R, Kuipers F (1991) The permanent bile fistula rat model. Progr Pharmacol Clin Pharmacol 8 127-145... 

GLIPIZIDE ANION EXCHANGE RESINS Glipizide absorption may be i by colestyramine Colestyramine interrupts the entero-hepatic circulation of glipizide Avoid co-administration... 

The SN-38 glucuronide can be deconjugated in the gut to active SN-38 by bacterial glucuronidases. This entero-hepatic circulation of SN-38 results in a further plasma peak, and SN-38 released within the gut lumen has been... 

Although the mechanism of this interaction is unknown, animal studies suggest that suppression of the entero-hepatic circulation of valproic acid may have been involved (136). 

Data regarding the distribution of DNT are limited to 2,4-DNT studies in animals. Following oral administration of 2,4-DNT to various laboratory species, the greatest concentrations of the chemical occurred in the liver, kidneys, and blood. Only small amounts were found in the brain, heart, and spleen. A biphasic increase in hepatic levels of 2,4-DNT in rats suggested that the chemical undergoes entero-hepatic circulation. 

The liver must be producing alkaline phosphatase to renew that on the outer surfaces of the bile canaliculi whose contents empty not into venules but into the common bile duct. The amount of alkaline phosphatase in bile is of a low order, and quantitatively can bear little comparison to that produced by the intestinal mucosa. There is the possibility, however, that the biliary alkaline phosphatase can be reabsorbed in an entero-hepatic circulation. 

Yasui, H. Yamaoka, K. Nakagawa, T. Alternative continuous infusion method for analysis of entero-hepatic circulation and biliary excretion of cefixime in the rat. J.Pharm.Sci., 1994, 83, 819-823... 

Tamoxifen given orally reaches peak plasma levels after 4—7 hours it has two elimination phases (half-lives of 7—14 hours and 4—11 days thus, 3—4 weeks of treatment are required to reach steady-state plasma levels). Tamoxifen is metabolized by hepatic CYPs, some of which it also induces. In humans, the potent antiestrogens 4-hydroxytamoxifen and endoxifen are produced in the liver. The major route of elimination involves N-demethylation and deamination. The drug undergoes entero-hepatic circulation, and excretion is primarily in the feces as conjugates of the deaminated metabolite. 

When the ileum is removed, bypassed, or severely diseased, the entero-hepatic circulation is again interrupted, which results in a diminished pool size (15) and increased daily fractional excretion rates from 0.12 to values of 0.5-1.5(16). 

Cholesterol is metabolised to form bile salts (Chapter 38) which are excreted in the bile duct. The bile salts emulsify fats in the intestine, which renders them available for hydrolysis by pancreatic lipase, which is secreted into the gut. About 95% of the bile salts are absorbed into the hepatic portal vein and are recycled to the Uver by the entero-hepatic circulation . About 5% of the bile salts ate lost in the faeces. 

Micro-organisms highly sensitive to inhibition by rifampin, include penicillin-sensitive as well as penicillin-resistant S. aureu , D. neu-moniae, group A streptococci, H. influenzae Proteus, M. tuberculosis in vitroand,in the mouse. Plasma levels above 2 pg/ml were attained in man between two and four hours after oral administration of a 300 mg dose of rifampin. A major portion of the drug is found in the bile in the form of 25-desacetyl rifampin with evidence of entero-hepatic circulation of this biologically active metabolite. 

The obligatory role of bile acids in the overall efficiency of cholesterol absorption from the intestine has been extensively documented, Prior to 1920, it had already been demonstrated that bile duct ligation[l] or bile diversion[2] in dogs, markedly diminished the capacity of the intestine to absorb cholesterol. In the 1950 s several laboratories reported that interruption of the normal entero-hepatic circulation of bile and its contained bile salts, resulted in a decrease in lipids in the thoracic duct l3onph of experimental animals[3,4], a marked reduction in the absorbability of oleic acid and of corn oil fatty acids[4], and a complete cessation of cholesterol absorption into lymph[5-7]. Complimentary data has been reported by others in humans with complete biliary obstruction[8], and in animals and humans using bile acid-sequestering anion exchange resins, such as cholestyramine[9,10],... 

A study of the relationship between dietary factors and breast tumor characteristics was carried out in premenopausal women (Touillaud et al., 2005). Tumors were characterized in terms of their estrogen receptor (ER) status. Tumors with ER-positive status, as compared to ER-negative, are known to respond to the proliferative effect of estrogen, and are more likely to react to endocrine therapy. In the study, a low intake of boron (0.8 mg/day) was associated with a lower risk of ER-negative tumors as compared to a higher intake (1.03 mg/day). A similar relationship was observed with phytochemicals, such as phytosterols and kaempferol. Although these data are preliminary, they suggest that the effect of boron is confounded by the presence of phytosterols that are known to interfere with the entero-hepatic circulation of steroids, steroid hormones, and cholesterol (Samman et al, 2004). 

The distribution of radioactivity in tissues and intestinal contents one hour after administration of 8a-[S-(N-acetyl)-L-cysteinyl]-D-[l- C]riboflavin is summarized in Table 2. That at least the flavinyl moiety must be absorbed from the gastrointestinal tract was indicated by the rapid and sequential appearance of a fraction of in those tissues, such as liver, that similarly reflect the uptake of [2- C]riboflavin. The rather rapid appearance of in kidney, especially after i.p. injection, was also typical for flavin localization and preceded excretion of a considerable fraction of the label. The considerable radioactivity in the small intestine and its contents after i.p., as well as per os, administration reflects entero-hepatic circulation. Only traces of 002 were exhaled within even... 

Examples of secretions appear in bile (Sato, 1962 Matsushiro, 1963) Tenhunen, 1965) and intestinal juice (Karunairatnum and Levvy, 1951 and sometimes in salivary secretions (Yamanaka et al., 1965 Murata and Miyaji, 1966 Harvey et at., 1966). Judging from its properties, e.g., pH, -glucuronidase activity in these fluids is probably due in part to bacterial infection. /S-G ueuronidase in bile probably plays some role in the entero-hepatic circulation of drugs (Williams el al., 1965) and hormones (Paschkis and llakoff, 1950 Knapstein et cU., 1966, 1967), and also may induce the formation of calcium bilirubinate stones (Maki el al., 1962 Saito, 1964 Sato el al., 1964 Maki, 1966). 

Part of the bile pigments are reabsorbed in the intestine and returned to the liver in the portal vein blood (entero-hepatic circulation). The greater part, however, is excreted by the intestine. 

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