Enterohepatic recycling

Clinical manifestation of vitamin B 2 deficiency is usually a result of absence of the gastric absorptive (intrinsic) factor. Dietary deficiency of vitamin B 2 is uncommon and may take 20 to 30 years to develop, even in healthy adults who foUow a strict vegetarian regimen. An effective enterohepatic recycling of the vitamin plus small amounts from bacterial sources and other contaminants greatly minimizes the risk of a complete dietary deficiency. Individuals who have a defect in vitamin B 2 absorption, however, may develop a deficiency within three to seven years. 

Combination therapy with a statin and BAR is rational because numbers of LDL-Rs are increased, leadingto greater degradation of LDL cholesterol intracellular synthesis of cholesterol is inhibited and enterohepatic recycling of bile acids is interrupted. 

A-Nitrosomorpholine and A-nitrosodiethanolamine are both converted in vivo to A-nitroso-A-2-hydroxyethylglycine, which is excreted in rodent urine. The recovery of A-nitroso-A-2-hydroxyethylglycine in 24-h urine was lower in rats (8%) than in mice or hamsters (11-14%) dosed intraperitoneally with A-nitrosodiethanolamine (5 mg/kg bw), which was also found in urine of all the species (Bonfanti et al, 1986). Biliary excretion (a minor route of elimination) and enterohepatic recycling of A-nitrosodiethanolamine and its metabolite A-nitroso-A-2-hydroxyethylglycine has been shown in rats after intravenous administration of 5 mg/kg bw A-nitrosodi-ethanolamine (Bonfanti et al, 1985). 

Bonfanti, M., Castelli, M.G., Fanelli, R. Airoldi, L. (1985) Enterohepatic recycling of 7V-nitrosodiethanolamine in rats. Food chem. Toxicol., 23, 1011-1013... 

Phenprocoumon undergoes enterohepatic recycling, and its elimination can be enhanced by ion exchange resins, sometimes with fatal consequences (19). 

Fibrates should be avoided in gallbladder disease or any form of obstructive jaundice because of the risk of stone formation. The extended therapeutic effect of gemfibrozil, which is due to enterohepatic recycling, may be reduced in obstructive jaundice. Fibrates may have an adverse effect on coagulation if used, the INR/PT should be monitored... 

Ezetimibe is well absorbed and rapidly glucuronidated [1]. The glucuro-nide undergoes extensive enterohepatic recycling, resulting in multiple peaks. It is more active than the parent drug [1]. 

Fenofibrate, ciprofibrate and bezafibrate are excreted primarily in the urine, either as unchanged drug or as metabolites. Gemfibrozil is extensively excreted in bile and its metabolites undergo enterohepatic recycling [19]. 

Ezetimibe undergoes extensive enterohepatic recycling and the amount recycled into the systemic circulation has been estimated at 17-20%... 

Fenofibrate and bezafibrate are excreted almost entirely in the urine and are more appropriate than gemfibrozil in obstructive jaundice. Gemfibrozil is significantly excreted in bile and undergoes enterohepatic recycling, to which part of its activity is due this would be reduced by obstructive jaundice. This may lead to a reduction in, or the elimination of, any secondary peaks. 

Much of the absorbed riboflavin is phosphorylated in the intestinal mucosa by flavokinase and enters the bloodstream as riboflavin phosphate this metabolic trapping is essential for concentrative uptake of riboflavin into en-terocytes (Gastaldi et al., 2000). Parenterally administered free riboflavin is also largely phosphorylated in the intestinal mucosa. It is not clear whether this is the result of enterohepatic recycling of the vitamin or simply uptake of free riboflavin into the intestinal mucosa from the bloodstream. 

The daily loss is about 0.1% of the body pool in subjects with normal intrinsic factor secretion and enterohepatic circulation of the vitamin (Section 10.7.2). On this basis, the requirement is 0.3 to 1.8 nmol (1 to 2.5 /xg) per day (Herbert, 1987b). This is probably a considerable overestimate of requirements, because parenteral administration of less than 0.3 nmol per day is adequate to maintain normal hematology in patients with pernicious anemia, in whom the enterohepatic recycling of the vitamin is grossly impaired. 

Enterohepatic recycling takes place, and eventually about 60% of a single dose is eliminated in the faeces urinary excretion of unchanged drug also occurs. The t) is 4 h after initial doses, but shortens on repeated dosing because rifampicin is a very effective er zyme inducer and increases its own metabolism (as well as that of several other drugs, see below). 

Colestyramine is an oral anion-exchange resin, which binds bile acids in the intestine. Bile acids are formed from cholesterol in the liver, pass into the gut in the bile and are largely reabsorbed at the terminal ileum. The total bile acid pool is only 3-5 g but, because such enterohepatic recycling takes place 5-10 times a day, on average 20-30 g of bile acid are delivered into the intestine every 24 hours. Bile acids bound to colestyramine are lost in the faeces and the depletion of the bile acid pool stimulates conversion of cholesterol to bile acid the result is a... 

Some drugs, such as ranitidine, cimetidine, and dipyridamole, after oral administration produce a blood concentration curve consisting of two peaks. This double-peak phenomenon is generally observed after the administration of a single dose to fasted patients. The rationale for the double-peak phenomenon has been attributed to variability in stomach emptying, variable intestinal motility, presence of food, enterohepatic recycling, or failure of a tablet... 

Elimination Renally cleared. Vh 2 days Vh 4 days in renal impairment). May also undergo enterohepatic recycling. Therapeutic plasma range O.S to 2 pg/L. 

Contraceptive efficacy can be decreased when taken concurrently with drugs that increase the metabolism of hormones (e.g., CYP450 inducers). Similarly, drugs that reduce enterohepatic recycling of COCs (e.g., tetracycline, penicillins) can also reduce efficacy. 

A search for potential prodrug forms of posaconazole b yielded a possible candidate. SCH 59884. The compound i> inactive in vitro but is dephosphorylated in vivo to yield Hit active 4-hydroxybutyrate ester. This compound is hydic-lyzed to the parent compound in the. serum. Posaconazok undergoes extensive enterohepatic recycling, and mosiul the dose is eliminated in the bile and feces. 

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