Efficiency of enterohepatic circulation, its determination and influence on drug bioavailability. 1999

S Horkovics-Kovats
Biochemie GmbH, Kundl, Austria.

A new approach has been developed to determine the factors that influence the balance of drug elimination from the body. This approach is based on 1. a six-compartment-model with compartments connected by different flow rates assuming kinetic processes of first order, 2. on solutions of geometric series and 3. on numerical solutions of a system of non-linear equations. In the model, different ways of drug elimination have been considered: renal, liver and fecal elimination of the drug and its metabolism in the liver. The organs have been characterized by their drug availabilities. Further, the metabolic activity of the liver, the efficiency of drug absorption and re-absorption from the gastrointestinal (GI) tract have been included. This paper identifies three events, characterized by their efficiencies--1. hepatic excretion, 2. elimination of drug from liver into the gall bladder in its non-metabolized form and 3. the re-absorption of the drug from GI tract--as necessary conditions of enterohepatic circulation of (EHC). The product of these efficiencies has been introduced as the efficiency of enterohepatic circulation. Further, the drug bioavailability as a function of the efficiency of EHC is presented. The study shows that--based on the total amounts of non-metabolized drug in urine after p.o. and i.v. administration to animals with and without cannulated bile duct and in the bile of cannulated animals--the efficiency of EHC, bioavailability of the drug, renal and hepatic availability of the drug, metabolic activity of the liver and efficiency of drug absorption and re-absorption from the gut can be determined. Additionally, it has been shown that, depending on the efficiency of enterohepatic circulation, small variabilities in drug pharmacokinetic properties can cause high variance of drug bioavailability. The publication points towards the efficiency of EHC as on a factor that plays a key role in establishing in vitro-in vivo correlation.

UI MeSH Term Description Entries
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D004364 Pharmaceutical Preparations Drugs intended for human or veterinary use, presented in their finished dosage form. Included here are materials used in the preparation and/or formulation of the finished dosage form. Drug,Drugs,Pharmaceutical,Pharmaceutical Preparation,Pharmaceutical Product,Pharmaceutic Preparations,Pharmaceutical Products,Pharmaceuticals,Preparations, Pharmaceutical,Preparation, Pharmaceutical,Preparations, Pharmaceutic,Product, Pharmaceutical,Products, Pharmaceutical
D004764 Enterohepatic Circulation Recycling through liver by excretion in bile, reabsorption from intestines (INTESTINAL REABSORPTION) into portal circulation, passage back into liver, and re-excretion in bile. Circulation, Enterohepatic,Entero-Hepatic Circulation,Circulation, Entero-Hepatic,Circulations, Entero-Hepatic,Circulations, Enterohepatic,Entero Hepatic Circulation,Entero-Hepatic Circulations,Enterohepatic Circulations
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000465 Algorithms A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. Algorithm
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001682 Biological Availability The extent to which the active ingredient of a drug dosage form becomes available at the site of drug action or in a biological medium believed to reflect accessibility to a site of action. Availability Equivalency,Bioavailability,Physiologic Availability,Availability, Biologic,Availability, Biological,Availability, Physiologic,Biologic Availability,Availabilities, Biologic,Availabilities, Biological,Availabilities, Physiologic,Availability Equivalencies,Bioavailabilities,Biologic Availabilities,Biological Availabilities,Equivalencies, Availability,Equivalency, Availability,Physiologic Availabilities
D016473 Gallbladder Emptying A process whereby bile is delivered from the gallbladder into the duodenum. The emptying is caused by both contraction of the gallbladder and relaxation of the sphincter mechanism at the choledochal terminus. Gall Bladder Emptying,Emptying, Gall Bladder,Emptying, Gallbladder

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