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Results for “Enterohepatic Circulation”

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At least 19 recordsLinked to original sources

PubMedDate not supplied

Role of enterohepatic circulation in the analgesic action of 1-alpha-acetylmethadol in the rat.

The enterohepatic circulation of 1-alpha-acetylmethadol (LAAM) was investigated in the rat. Bile containing 3H-LAAM metabolites was collected from a biliary cannulated donor rat after administration of 3H-LAAM (5 mg/kg, 15 muCi/kg, sc) and infused into the intestine of a double biliary-cannulated recipient rat for 1 hr, and tritium excreted into the bile of the recipient rat was monitored. Within 1 hr after the end of infusion significant radioactivity was found in the bile of the recipient rat and by 10 hr 50% of the infused dose of 3H had been re-excreted into bile. The contribution of enterohepatic circulation of LAAM metabolites to the analgesic action of LAAM was also assessed. Pretreatment of rats with neomycin sulfate was used as a method of decreasing enterohepatic circulation of biliary glucuronide conjugates of LAAM metabolites, and such pretreatment had no effect on LAAM analgesia (6 mg/kg) measured by the hot-plate method. In rats with a biliary fistula, a situation in which enterohepatic circulation was completely eliminated, the analgesic response to a dose of LAAM (6 mg/kg, sc) was not different from sham-operated control group. The above findings indicate that enterohepatic circulation of LAAM metabolites does not contribute to the intensity or duration of LAAM analgesia.

Analgesics↗

PubMed1977

The enterohepatic circulation of bile acids in man.

The enterohepatic circulation of bile acids may now be described in its broad outlines. Methodology presently available appears sufficient for overall characterization in health and disease. The challenge of the future is to gain insight into the control of the enterohepatic circulation so that new therapeutic approaches to liver, biliary and intestinal disease may be developed.

Amino Acids↗

PubMed1990

Analysis of enterohepatic circulation of cefixime in rat by fast inverse Laplace transform (FILT).

The enterohepatic circulation of cefixime in rat was evaluated by a nonlinear least square analysis program, MULTI(FILT), into which the fast inverse Laplace transform (FILT) was incorporated. The plasma time course in the bile duct-cannulated rat exhibited a biexponential curve after the rapid iv administration of cefixime. Several pharmacokinetic models for the enterohepatic circulation were constructed based on the recirculatory concept and the Laplace-transformed equations corresponding to these models were derived by means of the method of transfer function. The transformed equations were simultaneously fitted to the time courses of plasma concentration in rats with laparotomy and with bile duct cannula. The optimum model was selected based on the Akaike's information criterion (AIC). The local moment characteristics for a single pass through enterohepatic circulation were further calculated from the time courses of both the plasma concentration and the amount excreted into the bile. The recovery ratio (Fc) and the mean circulatory time (-tc) through a single pass of enterohepatic circulation were estimated 27.9% and 1.07 hr, respectively. The recovery ratio (Fa) and the mean absorption time (-tc) for the absorption process from the intestinal tract into the systemic circulation were 68.3% and 0.0234 hr, respectively. The recovery ratio (Fb) and the mean transit time (-tb) for the disposition process through the systemic circulation into the bile were 40.8% and 1.05 hr, respectively.

Animals↗

PubMedDate not supplied

Pharmacokinetic analysis of enterohepatic circulation of 4-[2-(4-isopropylbenzamido)ethoxy]benzoic acid. Effect of intramolecular rearrangement of its acyl glucuronide.

The enterohepatic circulation of 4-[2-(4-isopropylbenzamido)ethoxy]benzoic acid (PBAB) was studied in rats after an iv administration of 30 mg/kg. After the bolus injection, the PBAB concentrations in the plasma decreased rapidly, then increased to a peak concentration at 4 hr. Over a 6-hr period, 52% of the dose (Fe) was excreted in the bile as 1 beta-O-acyl glucuronide of PBAB (1 beta-PG). Elimination of PBAB from the plasma of bile duct-cannulated rats was more rapid than for the sham-operated rats. These results suggest that PBAB undergoes enterohepatic circulation. The equation for an enterohepatic circulation model was fitted to the plasma PBAB concentrations for intact rats using the program MULTI (FILT) to estimate the single circulating fraction (Fc) (bile----intestine----systemic circulation). The Fc value was 0.072, which means that 7.2% of the dose was reabsorbed to systemic circulation during the first cycle. The fraction (Fa) reabsorbed from small intestine to systemic circulation during first cycle can be estimated by the formula Fa = Fo/Fa. The Fa value obtained was 14% of the dose, which was smaller than the Fa' (26% of the dose) standing for systemic availability of PBAB after oral dosing. When 1 beta-PG was incubated with bile for 2 hr, 79% was transformed to beta-glucuronidase-resistant isomers by intramolecular acyl migration. We consider that the acyl migration of 1 beta-PG in the small intestine or bile causes the difference between Fa and Fa' values, and decreases the enterohepatic circulation of PBAB.

Animals↗

PubMed1977

[Enterohepatic circulation of bile acids and biliary lipid secretion].

The enterohepatic circulation of bile acids in man is reviewed. The chemistry of biliary bile acids is summarized and related to the formation of primary bile acids in the liver and secondary bile acids in the intestinal lumen. New findings showing that lithocholic acid is absorbed in man are presented, and the recent experiments showing that lithocholic acid is extensively sulfated are reviewed. The consistent hepatotoxicity of chenodeoxycholic acid in the rhesus monkey, which contrasts with its non-toxicity in man, is explained by the inability of the rhesus monkey to sulfate abosrbed lithocholic acid; this accumulates in the enterohepatic circulation of the monkey causing liver damage. In man, absorbed lithocholic acid is rapidly sulfated, and the sulfated conjugates are excreted fecally without enterohepatic cycling. The physical chemistry of bile is highlighted, and it is shown that the saturation of bile with cholesterol depends on the amount of bile acids passing through the liver: at low bile acid flow rates, such as occurs during overnight fasting, bile is supersaturated in both gallstone and healthy persons. Chenodeoxycholic acid decreases cholesterol secretion into bile, renders bile unsaturated during most of the day and night, and thus induces gallstone dissolution.

Animals↗

PubMed1990

Factors affecting the enterohepatic circulation of oral contraceptive steroids.

Oral contraceptive steroids may undergo enterohepatic circulation, but it is relevant for only estrogens, because these compounds can be directly conjugated in the liver. Animal studies show convincing evidence of the importance of the enterohepatic circulation, but studies in humans are much less convincing. The importance of the route and the rate of metabolism of ethinyl estradiol are reviewed. Some antibiotics have been reported anecdotally to reduce the efficacy of oral contraceptive steroids, but controlled studies have not confirmed this observation. Although gut flora are altered by oral antibiotics, the blood levels of ethinyl estradiol are not reduced, and one antibiotic at least (cotrimoxazole) enhances the activity of ethinyl estradiol.

Anti-Bacterial Agents↗

PubMed1977

Metabolism of steroid and amino acid moieties of conjugated bile acids in man. V. Equations for the perturbed enterohepatic circulation and their application.

Equations previously developed to describe the enterohepatic circulation of the major biliary bile acids in man (Gastroenterology 67:887, 1974) were modified in order to predict the effect on biliary bile acid composition and pattern of amino acid conjugation after prototypic perturbations of the enterohepatic circulation in man. For the steroid moiety, the effects of bile acid feeding, increased recycling frequency, decreased intestinal conservation, and increased dehydroxylation were simulated. For the glycine or taurine moiety, the effect of increased deconjugation or preferential loss of one of the amino acid moieties was simulated. For the steroid moiety, the steady state biliary bile acid composition reflects the balance between input and conservation for each bile acid. Similarly, the distribution of bile acids between glycine and taurine conjugates reflects the balance between conjugation and conservation for each amino acid moiety. Because these values may vary widely and independently, analysis of biliary bile acid composition in terms of the steroid moiety or the glycine-taurine ratio per se cannot be used to infer the relative rates of input or conjugation.

Amino Acids↗

PubMed1976

The effect of diether phosphatidylcholine on the enterohepatic circulation of biliary sterols.

The effect of diether phosphatidylcholine on the enterohepatic circulation of bile salts and cholesterol was determined using the bile duct cannulated rat. Animals were infused intraduodenally with a solution containing radioactive bile salts and cholesterol. Phospholipid was also present in the infusate. In control animals it was supplied by pig liver phosphatidylcholine (diester). For experiments, equimolar amounts of diether phosphatidylcholine were used. No difference was observed between control and experimental groups for absorption and subsequent secretion of bile salts into bile. Significantly less cholesterol was absorbed, however, by experimental rats. This was correlated with a decreased secretion of radioactive cholesterol into bile. In controls, almost 14% of the administered dose of cholesterol appeared in bile over the period of infusion while the value for experimentals was 5%. It is concluded that diether phosphatidylcholine inhibits the enterohepatic circulation of cholesterol but not of bile salts.

Animals↗

PubMed1992

[Pharmacokinetic analysis of enterohepatic circulation of piroxicam in rabbits].

The concentration (c)-time (t) curves of piroxicam showed double peaks following iv 10 mg dose to 4 rabbits. A new mathematical model of enterohepatic circulation was proposed to explain this double-peak phenomenon and showed good agreement with data. This model provides not only the common pharmacokinetic parameters: T1/2 = 1.12 +/- 0.32 h, V1 = 0.64 +/- 0.12 L, AUC = 34.7 +/- 7.8 micrograms.h-1.ml-1, but also the parameters of enterohepatic circulation of piroxicam: the cycling amount of drug Db = 3.9 +/- 1.4 mg, reabsorption fraction Fb = 0.50 +/- 0.04, reabsorption rate constant Ka = 2.55 +/- 0.50 h-1. It is indicated in this study that enterohepatic circulation results in a 20% average increase of the effective amount of piroxicam.

Animals↗

PubMed1979

John Caffey Award: lithiasis due to interruption of the enterohepatic circulation of bile salts.

Bile salts are formed from cholesterol and conjugated in the liver, excreted via the biliary system into the duodenum, reabsorbed in the ileum, stored temporarily in the hepatic bile salt pool, and reexcreted into the biliary system. This normal enterohepatic circulation of bile salts is both efficient and rapid. Interruption of the enterohepatic circulation of bile salts may cause cholesterol cholelithiasis or oxalate urolithiasis. Clinical and radiologic features of pediatric patients with gallstones and urolithiasis secondary to abnormalities of the ileum are reported. The pathophysiology of lithiasis due to interruption of the enterohepatic circulation of bile salts is discussed. This enteric cause is included in the differential diagnosis of cholelithiasis and urolithiasis in infants and children.

Bile Acids and Salts↗

PubMed1977

The enterohepatic circulation of conjugated bile acids in healthy man: quantitative description and functions.

A multicompartmental model describing the enterohepatic circulation of conjugated bile acids in man under steady-state conditions is proposed. The model encompasses conjugation; deconjugation and reconjugation; dehydroxylation; sulfation, desulfation and resulfation; dehydrogenation; and stereoselective rehydrogenation. A dynamic description of the enterohepatic circulation and a brief description of bile acid functions in health and dysfunctions in disease are also discussed.

Bile↗

PubMed1992

Enterohepatic circulation is essential for regular cycling of duodenal migrating motor complexes in dogs.

The role of enterohepatic circulation and specific bile acids in the initiation and caudad migration of duodenal migrating motor complexes (MMCs) was investigated in conscious dogs. All dogs had spontaneous duodenal MMCs that migrated to the terminal ileum when bile flow was intact. During the first 3 days after total external biliary diversion, no MMCs originated in the duodenum. Instead, all MMCs originated in the jejunum and migrated to the ileum. During the next 4 days of total external biliary diversion, 81% of the MMCs originated in the jejunum and 19% in the duodenum. When normal bile flow was restored after 9 days of total external biliary diversion, regular duodenal MMCs resumed after a delay of 126 +/- 27 minutes. Perfusion of individual bile acids or dogs' own bile, but not saline or alkaline solution, into the duodenum or perfusion of dogs' own bile directly into the ileum during total external biliary diversion restarted duodenal MMCs with a time lag of about 2 hours. The authors conclude that intact enterohepatic circulation is essential for the initiation of regular duodenal MMCs.

Animals↗

PubMed1992

Distinct distributions of D-erythro-neopterin in arteries and veins and its recovery by an enterohepatic circulation.

Large amounts of D-erythro-neopterin, a pteridine derivative, are formed from guanosine triphosphate (GTP) by human macrophages upon stimulation with interferon-gamma. In addition, in humans a basal neopterin level in all body fluids is evident also in absence of immunological stimuli. Extremely high concentrations of D-erythro-neopterin were detected in biliary fluid. We therefore investigated, if an enterohepatic circulation might exist for this substance. We quantified concentrations of pteridines in serum obtained from various vessels and in biliary fluid. Samples were collected during surgery of five patients with duodenal ulcer or adenocarcinoma of the stomach. Our data clearly demonstrate the existence of an enterohepatic circulation for the recovery of neopterin which seems to be specific for this substance. The relative distributions of neopterin concentrations in the gastrointestinal tract and vessels were seen invariably in all patients and were consistent with findings in five corpses examined post mortem. In addition, significantly higher neopterin concentrations, were found in arteries than in veins. The data indicate that neopterin derivatives are consumed in the peripheral capillary system and an enterohepatic circulation is established to maintain constant blood levels of neopterin derivatives. Furthermore, we suppose that the liver is the source of constitutive neopterin concentrations.

Adenocarcinoma↗

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↗

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↗

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↗

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↗

PubMed1991

Acute effects of HMG-CoA reductase inhibitors on biliary lipids in patients with interrupted enterohepatic circulation.

HMG-CoA reductase inhibitors decrease serum cholesterol by inhibiting hepatic cholesterol synthesis, but their influence on biliary lipids is not well characterized. In the present study Pravastatin (80 mg) was administered as a single oral dose to 10 patients with external bile fistula, after 1 week of interruption of the enterohepatic circulation, in order to assess the effect of inhibition of hepatic cholesterol synthesis on biliary lipids in conditions of stimulated bile acid synthesis. Bile was collected every hour for 12 h. On the day before, the same procedure was applied with a placebo, and collected bile used as control. Pravastatin decreased both bile acid and phospholipid concentration to about 60% of basal values; this change was still significant after 10 h. Cholesterol concentration was also decreased to about 70% of basal values, but this change was significant only from the 5th to the 7th h. The per cent of cholic and chenodeoxycholic acid was not affected by the drug, but the ratio of glyco- to tauroconjugated bile acids was decreased to about half the initial values. Bilirubin concentration exhibited a late increase, suggesting a reduction in the bile flow. These results suggest that, in patients with interrupted enterohepatic circulation, biliary excretion of bile acids can be largely dependent on hepatic cholesterol synthesis.

Adult↗