SEARCH · PubMed Health

Results for “Enterohepatic Circulation”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 73 records · Page 4Linked to original sources

PubMedDate not supplied

The pharmacokinetics of exaprolol and propranolol in rats with interrupted enterohepatic circulation.

The pharmacokinetics of two beta adrenoceptor blocking drugs, exaprolol and propranolol, in rats with interrupted enterohepatic circulation was studied. The tritium-labelled drugs were given intravenously to four groups of rats: control, bile-duct cannulated, bile-duct ligated, and pretreated with neomycin. Plasma levels and excretion were observed up to 96 h after administration. The pharmacokinetic parameters show an enhanced plasma elimination of both drugs at interrupted enterohepatic circulation compared to the control group. Significant changes were observed in the excretion pattern with bile-duct cannulated and bile-duct ligated rats, while the total radioactivity excreted in urine and faeces does not differ between control and neomycin pretreated rats.

Adrenergic beta-Antagonists↗

PubMed1978

Assessment of enterohepatic circulation of 3H-digoxin with a minimal interruption technique.

The biliary excretion of 3H-digoxin in rats prepared for bile sampling with minimal interruption of the enterohepatic circulation was compared with that in rats with complete interruption after intraduodenal or intravenous administration. Following dosage by either route, significantly more radioactivity was recovered from animals with nearly intact enterohepatic circulation. The method described allows direct measurement of this cycle in unanesthetized animals without the consequences of bile depletion.

Animals↗

PubMed2003

Cyclosporin a and enterohepatic circulation of bile salts in rats: decreased cholate synthesis but increased intestinal reabsorption.

Cyclosporin A (CsA) has been shown to inhibit synthesis and hepatobiliary transport of bile salts. However, effects of CsA on the enterohepatic circulation of bile salts in vivo are largely unknown. We characterized the effects of CsA on the enterohepatic circulation of cholate, with respect to synthesis rate, pool size, cycling time, intestinal absorption, and the expression of relevant transporters in liver and intestine in rats. CsA (1 mg. 100 g(-1). day(-1) s.c.) or its solvent was administered daily to male rats for 10 days. Cholate synthesis rate and pool size were determined by a 2H4-cholate dilution technique. Bile and feces were collected for determination of cholate and total bile salts, respectively. Cycling time and intestinal absorption of cholate were calculated. The mRNA levels and corresponding transporter protein levels in liver and intestine were assessed by real-time polymerase chain reaction and Western analysis, respectively. CsA treatment decreased cholate synthesis rate by 71%, but did not affect pool size or cycling time. CsA reduced the amount of cholate lost per enterohepatic cycle by approximately 70%. Protein levels of the apical sodium-dependent bile salt transporter (Asbt) were 2-fold increased in distal ileum of CsA-treated rats, due to post-transcriptional events. In conclusion, chronic CsA treatment markedly reduces cholate synthesis rate in rats, but does not affect cholate pool size or cycling time. Our results strongly suggest that CsA enhances efficacy of intestinal cholate reabsorption through increased Asbt protein expression in the distal ileum, which contributes to maintenance of cholate pool size in CsA-treated rats.

Animals↗

PubMed1984

Enterohepatic circulation of clioquinol in the rat.

The existence of the enterohepatic circulation (EHC) of clioquinol was confirmed by using paired rats, donor and recipient, which were connected to each other with a bile duct-to-duodenum cannula. The concentrations of clioquinol and its metabolites appearing in the plasma of the recipient following intraduodenal 10 mg/kg dose of clioquinol to the donor were fairly low. However, within 24 h after the administration ca. 12% of the dose was reexcreted in the bile of the recipient as clioquinol glucuronide and ca. 2% in the urine as clioquinol sulfate. From these results and the data of biliary excretion in our previous paper, the glucuronide was found to play a role on the EHC. Further, both in vitro and in situ results suggested that clioquinol glucuronide excreted in the bile may be absorbed partially after return to the parent drug in the intestinal tract and partially as such without deconjugation.

Animals↗

PubMed2006

Characterization of intestinal absorption and enterohepatic circulation of mycophenolic Acid and its 7-O-glucuronide in rats.

To assess the mechanism of gastrointestinal disorders by mycophenolate mofetil (MMF), the intestinal absorption and enterohepatic circulation of mycophenolic acid (MPA), an active metabolite of MMF, and its 7-O-glucuronide (MPAG) were investigated using rat intestinal loops and a linked-rat model. The stability of MPAG in the intestinal fluids, the toxicity of MPA and MPAG to intestinal mucosa, and biliary excretion of MPAG in rats with acute renal failure (ARF) were also characterized. MPA was rapidly and extensively absorbed from the rat intestine whereas MPAG was much less absorbable. When MPA was administered intravenously to bile-donor rats, 1.2% of dose was excreted in bile of receiver rats exclusively as MPAG during 4 h. MPAG was minimally deconjugated in the intestinal fluids. MPAG, but not MPA, significantly enhanced the release of lactate dehydrogenase from intestinal mucosa. When MPA was intravenously administered to ARF rats, the biliary excretion of MPAG significantly increased, compared with that in normal rats. These results demonstrated that MPAG accumulated in the intestinal lumen following biliary excretion and exerted some toxic effect on the intestinal mucosa. It was also suggested that enterohepatic circulation of MPAG under renal dysfunction increased the risk of gastrointestinal disorders due to MPAG.

Acute Kidney Injury↗

PubMed1983

The enterohepatic circulation of the metabolites of 17 alpha-ethynyl[3H]estradiol in the rat.

The biliary metabolites of 17 alpha-ethynyl[3H]estradiol (3H-EE2) and their enterohepatic circulation were studied in female rats. Rapid and extensive elimination of radioactivity in bile followed i.v. administration of 3H-EE2. The metabolites consisted largely of beta-glucuronides of 2-hydroxy-EE2 and, to a lesser extent, 2-methoxy-EE2. Intraduodenally infused radiolabelled biliary metabolites underwent enterohepatic circulation; 15 +/- 6% (mean +/- S.D., n = 4) of the 3H was excreted in the bile of the recipient rats in 5.5 h. The metabolites excreted by the recipients were qualitatively and quantitatively similar to the infused metabolites. The 1(4)-glutathione adduct of 2-hydroxy-EE2 was synthesized, but was not observed in either the donors' or recipients' bile.

Animals↗

PubMed1987

Enterohepatic circulation of N-acetyl-leukotriene E4.

N-Acetyl-leukotriene E4, the end product of leukotriene C4 metabolism in the mercapturic acid pathway, was rapidly eliminated from the blood circulation into the bile of rats. Part of the N-acetyl-leukotriene E4 secreted from bile into the intestine underwent enterohepatic circulation. Leukotriene absorption occurred from the small intestine and from the colon. Biliary and urinary excretion within 5.5 h amounted to 15 and 2%, respectively, of the intraduodenally administered N-acetyl- 3H leukotriene E4 in animals anesthetized with ketamine. HPLC analyses indicated that 35% of the biliary radioactivity corresponded to unchanged N-acetyl-3H leukotriene E4, while 65% in bile and 100% in urine were polar metabolites. Enterohepatic circulation extends the biological half-life of N-acetyl-leukotriene E4.

Animals↗

PubMed1981

Crohn's disease and the enterohepatic circulation.

Crohn's disease is a chronic inflammatory process which may affect any part of the alimentary tract. This cause is unknown. Overall the distribution of the lesions coincides with that of the enterohepatic circulation. A possible causative agent is a metabolic or ingested substance excreted into the bile in the form of a polar and inactive conjugates. The agent would have to have a prolonged half life in the enterohepatic circulation. In the ileocaecal region and elsewhere when bacterial colonisation occurs the inactive conjugates may be hydrolysed to release the active substance. This would act locally on the intestinal tissues either as a result of altering the physicochemistry of mucus or during passage through the gut wall.

Cecum↗

PubMed1983

Portacaval shunt and measurement of canine bile acid enterohepatic circulation: effects of cholecystectomy.

Studies were made of the usefulness of serial serum bile acid determinations in dogs with end-to-side portacaval shunt for determining relative rates of bile acid enterohepatic circulation (EHC). Studies in intact and cholecystectomized dogs with shunt showed that bile acid EHC in fasting cholecystectomized animals was about three times faster than in intacts. As expected, feeding greatly increased EHC in intacts, but caused smaller but definite increases in cholecystectomized animals. Cholecystokinin (Kinevac) administration caused transient increases in intact dog bile acid EHC, but had no effect in cholecystectomized animals. These results confirm most previous studies and demonstrate that the method is sensitive and useful for comparing rates of bile acid enterohepatic circulation under different circumstances.

Animals↗

PubMed1977

Dynamics of the enterohepatic circulation of the glycine conjugates of cholic, chenodeoxycholic, deoxycholic, and sulfolithocholic acid in man.

Highly sensitive and specific radioimmunoassays for cholylglycine, chenodeoxycholylglycine, deoxycholylglycine, and sulfolithocholylglycine have been used to study the kinetics of the enterohepatic circulation of these conjugated bile acids in 8 healthy subjects. Venous blood samples were collected over a 32-hr period, during which time the subjects ate three meals. Serum levels of cholylglycine and chenodeoxycholylglycine rose after each meal, and reached their maximum level within 30 to 60 min. A second chenodeoxycholylglycine peak occurred 2 to 3 hr after the first two meals in all subjects; a second peak was also found for cholylglycine in 3 of the 8 subjects. Serum deoxycholylglycine levels also rose postprandially; the peak level generally occurred 30 min later than that of cholylglycine. Serum sulfolithocholylglycine levels did not alter significantly after meals. The data indicate that the dynamics of the enterohepatic circulation of individual serum bile acids differ both quantitatively and qualitatively.

Adult↗

PubMed1982

A practical method for monitoring drug excretion and enterohepatic circulation in the rat.

An improved experimental design for studying the enterohepatic circulation of drugs in a pair of bile duct-duodenum cannula-linked rats is described. By housing the rats in individual metabolism cages and using a peristaltic pump to immediately deliver bile secreted by the donor directly into the duodenum of the recipient, the method permits a realistic approximation of biliary excretion and reabsorption in intact animals for periods up to 96 hours.

Animals↗

PubMed1975

Metabolism of lithocholate in healthy man. II. Enterohepatic circulation.

Studies were carried out in healthy subjects to characterize the enterohepatic circulation of lithocholate and its metabolites. When mixed with bile and infused into the jejunum, radiolabeled lithocholylglycine was absorbed more rapidly and more efficiently than sulfolithocholylglycine, based on recovery from bile. When these metabolites were administered at 1800 hr in a liquid test meal containing radiolabeled taurocholate as an absorbable marker, 60% of lithocholylglycine was conserved, based on recovery of radioactivity in fasting bile the following morning, but only 20% of sulfolithocholylglycine was conserved. Iotope dilution studies in 4 subjects showed that daily input of lithocholate into the bile acid pool averaged 100 mg per day, about one-third to one-half of the chenodeoxycholic acid synthesis, but the t 1/2 was extremely short (0.74 day). The small lithocholate pool (about 100 mg) could be explained by rapid fecal excretion caused by sulfation which decreases passive absorption in the jejunum and active absorption in the ileum. Experiments with [35S]sulfo- [3H]lithocholylglycine indicated little desulfation during enterohepatic cycling but rapid desulfation in the distal intestine, with absorption of 35S (presumably as sulfate) followed by urinary excretion. A decreasing 35S:3H ratio in bile indicated that some steroid moiety was conserved to be resulfated. These studies indicate that considerable lithocholate is absorbed from the distal intestine in healthy subjects but efficient sulfation results in rapid fecal excretion, so that the total lithocholate pool remains small. A multicompartment model, previously used to describe the metabolism of the steroid and amino acid moieties of the major conjugated biliary bile acids, was extended to encompass lithocholyl conjugates and their sulfates.

Chenodeoxycholic Acid↗

PubMed1997

CCK-8 infusion increases plasma LMW alkaline phosphatase coincident with enterohepatic circulation of bile acids.

Bile acids may facilitate the release of liver alkaline phosphatase (ALP) from its hydrophobic membrane anchor. The purpose of this study was to determine whether such a facilitatory role could be observed during the enterohepatic circulation of bile acids in dogs. Increased hepatic ALP activity was induced in four dogs by daily injections of 4 mg.kg-1.day-1 of prednisone for 10 days. Intravenous infusions of cholecystokinin octapeptide (CCK-8) were given before treatment and on treatment days 3, 5, 7, and 10 to induce gallbladder emptying and the enterohepatic circulation of bile acids. Blood samples were taken hourly for 4 h before and for 4 h after CCK-8 infusion. These showed that plasma ALP activity increased significantly only after CCK-8 infusion. Gel exclusion chromatography, polyacrylamide gel electrophoresis, and octyl Sepharose phase separation showed that the increased ALP activity was a hydrophilic, low-molecular-weight (LMW) isoform, which is consistent with phospholipase release. Histochemical staining of endogenous ALP activity showed increased ALP activity over sinusoidal surfaces of prednisone-treated dogs. There was also an increased serum-to-tissue ratio of ALP activity in the prednisone-treated dogs, suggestive of increased release of ALP into blood. It was concluded that bile acids probably play a facilitatory role in the enzymatic release of ALP from the sinusoidal surface of hepatocytes, which may be accentuated by the presence of increased amounts of ALP on the sinusoidal surface in some disease states.

Alkaline Phosphatase↗

PubMed1993

Influence of poly(DL-lactide) nanocapsules on the biliary clearance and enterohepatic circulation of indomethacin in the rabbit.

Following intravenous administration, the uptake of colloidal drug carriers by cells of the mononuclear phagocyte system, mainly the Kuppfer cells, may concentrate an encapsulated drug close to the liver parenchymal cells and facilitate its biliary excretion and enterohepatic circulation. To test this hypothesis indomethacin was administered (10 mg/kg) in four groups of 10 rabbits each by intravenous infusion at a constant rate over 2 hr, either in its free form (aqueous solution) or as nanocapsules prepared from preformed poly(DL-lactide). Unchanged drug was assayed in plasma of the two control (sham-operated) groups and in both plasma and bile of the two bile-cannulated groups. Pharmacokinetic analysis led to the conclusion that the uptake of nanocapsules by liver macrophages reduces the concentration of the drug by enhancing its total clearance. This enhancement was due to an increase in biliary clearance, as a result of parallel increases in bile concentration and biliary excretion of the drug. It was also demonstrated that nanocapsules enhance the enterohepatic circulation of indomethacin.

Animals↗

PubMedDate not supplied

Radio-immunoassay for formyl methionyl leucyl phenylalanine. II. Demonstration of an enterohepatic circulation of immunoreactive bacterial chemotactic peptides in man.

Bacterial chemotactic peptides (F-met-oligopeptides) are secreted by several species of commensal enteric bacteria and can be assayed by bioassay techniques in human colonic luminal fluid. We have previously demonstrated intestinal absorption and enterohepatic circulation of radiolabelled F-met peptides introduced into rat colon, and an eightfold increase in absorption and biliary excretion in rats with experimental colitis. This paper describes the application of a radio-immunoassay to measurements of formyl oligopeptides in human faecal dialysates, colonic and systemic venous blood and bile. All samples were fractionated by reverse-phase high performance liquid chromatography (HPLC) prior to assay. Immunoreactivity was found in faecal dialysates (5-700 nmol/L F-met-leu-phe equivalents) and bile samples (3-150 nmol/L) from normal subjects. After HPLC fractionation, up to five distinct peaks of immunoreactivity were identified. One of these co-chromatographed with authentic F-met-leu-phe; the others probably represented either closely related peptides or peptides of different chain lengths originating from the same F-met-leu-phe precursor protein. Colonic venous blood from two patients with ulcerative colitis contained immunoreactive peptide (10-30 nmol/L) and substantial immunoreactivity was found in ileostomy fluid and bile from two patients with primary sclerosing cholangitis. These results suggest the presence of an enterohepatic circulation of bacterial F-met oligopeptides in man and provide a basis for studies of the role of such pro-inflammatory peptides in patients with inflammatory bowel disease and associated hepatobiliary disorders.

Animals↗

PubMed1996

Moment analysis of stereoselective enterohepatic circulation and unidirectional chiral inversion of ketoprofen enantiomers in rat.

The stereoselective enterohepatic circulation (EHC) and the synchronous chiral inversion of ketoprofen enantiomer in rat were evaluated by moment analysis based on the recirculatory concept. (R)-(-)- and (S)-(+)-ketoprofen were independently administered into rats, and the plasma and bile concentrations of both enantiomers were determined by a column-switching HPLC. (S)-Ketoprofen was generated by the chiral inversion from (R)-ketoprofen, whereas (R)-ketoprofen was not generated from (S)-ketoprofen. Within 30 min after intravenous administrations, the plasma time courses of R- and S-enantiomers were almost the same between rats with laparotomy and those with bile-duct cannula. After 30 min, the plasma concentrations in rats with laparotomy were significantly higher than those in rats with bile-duct cannula. The Laplace-transformed equations for stereoselective EHC and the synchronous chiral inversion were derived by means of the transfer function method on the basis of the recirculatory theory. The global moments (AUC and MRT) which were derived directly from the transformed equations were related to the local moments for the single EHC. The recirculation ratios of (R)- and (S)-ketoprofen for the single EHC were estimated to be 15.4% and 63.6%, respectively. The absorption ratios of (R)- and (S)-ketoprofen for the absorption process from the gastrointestinal tract into the systemic circulation were 87.0% and 83.8%, respectively. The biliary excretion rations of (R)- and (S)-ketoprofen for the disposition process through the systemic circulation into the bile were 17.7% and 75.8%, respectively. The chiral inversion ratio from (R)-ketoprofen into (S)-ketoprofen was 59.5%. The complicated disposition of ketoprofen, i.e., the simultaneous EHC and chiral inversion, was able to be analyzed by a moment method in a simple way.

Animals↗

PubMed2003

Enterohepatic circulation of bile salts in farnesoid X receptor-deficient mice: efficient intestinal bile salt absorption in the absence of ileal bile acid-binding protein.

The bile salt-activated farnesoid X receptor (FXR; NR1H4) controls expression of several genes considered crucial in maintenance of bile salt homeostasis. We evaluated the physiological consequences of FXR deficiency on bile formation and on the kinetics of the enterohepatic circulation of cholate, the major bile salt species in mice. The pool size, fractional turnover rate, synthesis rate, and intestinal absorption of cholate were determined by stable isotope dilution and were related to expression of relevant transporters in the livers and intestines of FXR-deficient (Fxr-/-) mice. Fxr-/- mice showed only mildly elevated plasma bile salt concentrations associated with a 2.4-fold higher biliary bile salt output, whereas hepatic mRNA levels of the bile salt export pump were decreased. Cholate pool size and total bile salt pool size were increased by 67 and 39%, respectively, in Fxr-/- mice compared with wild-type mice. The cholate synthesis rate was increased by 85% in Fxr-/- mice, coinciding with a 2.5-fold increase in cholesterol 7alpha-hydroxylase (Cyp7a1) and unchanged sterol 12alpha-hydroxylase (Cyp8b1) expression in the liver. Despite a complete absence of ileal bile acid-binding protein mRNA and protein, the fractional turnover rate and cycling time of the cholate pool were not affected. The calculated amount of cholate reabsorbed from the intestine per day was approximately 2-fold higher in Fxr-/- mice than in wild-type mice. Thus, the absence of FXR in mice is associated with defective feedback inhibition of hepatic cholate synthesis, which leads to enlargement of the circulating cholate pool with an unaltered fractional turnover rate. The absence of ileal bile acid-binding protein does not negatively interfere with the enterohepatic circulation of cholate in mice.

Animals↗

PubMed2006

[Pharmacokinetic model for the enterohepatic circulation of mycophenolic acid].

AIM: To develop a pharmacokinetic model for the enterohepatic circulation of mycophenolic acid (MPA). METHODS: Twenty healthy volunteers were orally given a single dose of 500 mg mycophenolate mofetil. Plasma samples were collected during 48 hours and MPA concentration was measured by HPLC method. Pharmacokinetic (PK) model was established based on physiological and biopharmaceutical consideration and PK parameters were obtained using nonlinear mixed effect model. RESULTS: The proposed model included an intestinal compartment and gall bladder compartment in addition to the central compartment. The predicted time-concentration curve and AUC0-t, Cmax, Tmax estimated by the established model were in agreement with the observations. CONCLUSION: The established model was well defined for the MPA disposition and could afford a useful approach for the further clinical investigation.

Adult↗