Biliary elimination and hepatic disposition of a new fluoroquinolone, temafloxacin: experimental evaluation. 1990

J M Brogard, and C Koechlin, and J F Westphal, and J F Blicklé, and M Dorner, and F Jehl
Department of Internal Medicine, Medical B Clinic, Strasbourg, France.

Temafloxacin is a new quinolone derivative presently under evaluation. Its pharmacokinetic profile, and particularly its biliary elimination and hepatic disposition, remains undefined. The present study describes an experimental approach to this issue. Six isolated rabbit liver preparations were perfused for 3h (h) with reconstituted blood in a closed circuit; 10 mg of temafloxacin were added to the circulating blood at the onset of the procedure. Bile was recovered throughout the experiments and liver fragments were taken at the conclusion. Assays were carried out by high-performance liquid chromatography. Pharmacokinetic analysis was performed with reference to a monocompartmental open model. Under these conditions, the serum half-life of temafloxacin was 3.1 and the maximal biliary concentration of 19.3 +/- SEM 3.1 micrograms/ml was reached between 30 and 60 min; the cumulative biliary elimination (0-3 h) amounted to 92 +/- 16 micrograms (0.9% of the added dose). Total and hepatobiliary clearances were calculated as respectively 134 and 2.38 ml/h and the hepatobiliary elimination rate as 0.0042 (h-1). At the end of the procedure, 25.7 +/- 3.5% of the added dose of temafloxacin was still present in the circulating blood, and 13.7 +/- 2.4% in the liver. Degradation of the antibiotic in the perfusion device concerned only 2.4% of the dose. The percentage of temafloxacin undergoing hepatic biotransformation, determined by subtraction, was high (57.3%). Under these experimental conditions, temafloxacin appears to be particularly stable in serum, poorly eliminated as parent compound in the bile, highly fixed in the liver and above all subject to a probable hepatic biotransformation. Extrapolation of these experimental data to other species or to the whole organism would be hazardous, but these results should stimulate studies on a possible hepatic metabolism of this new trifluoroquinolone in man.

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
D008657 Metabolic Clearance Rate Volume of biological fluid completely cleared of drug metabolites as measured in unit time. Elimination occurs as a result of metabolic processes in the kidney, liver, saliva, sweat, intestine, heart, brain, or other site. Total Body Clearance Rate,Clearance Rate, Metabolic,Clearance Rates, Metabolic,Metabolic Clearance Rates,Rate, Metabolic Clearance,Rates, Metabolic Clearance
D010477 Perfusion Treatment process involving the injection of fluid into an organ or tissue. Perfusions
D011817 Rabbits A burrowing plant-eating mammal with hind limbs that are longer than its fore limbs. It belongs to the family Leporidae of the order Lagomorpha, and in contrast to hares, possesses 22 instead of 24 pairs of chromosomes. Belgian Hare,New Zealand Rabbit,New Zealand Rabbits,New Zealand White Rabbit,Rabbit,Rabbit, Domestic,Chinchilla Rabbits,NZW Rabbits,New Zealand White Rabbits,Oryctolagus cuniculus,Chinchilla Rabbit,Domestic Rabbit,Domestic Rabbits,Hare, Belgian,NZW Rabbit,Rabbit, Chinchilla,Rabbit, NZW,Rabbit, New Zealand,Rabbits, Chinchilla,Rabbits, Domestic,Rabbits, NZW,Rabbits, New Zealand,Zealand Rabbit, New,Zealand Rabbits, New,cuniculus, Oryctolagus
D002853 Chromatography, Liquid Chromatographic techniques in which the mobile phase is a liquid. Liquid Chromatography
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
D000890 Anti-Infective Agents Substances that prevent infectious agents or organisms from spreading or kill infectious agents in order to prevent the spread of infection. Anti-Infective Agent,Anti-Microbial Agent,Antimicrobial Agent,Microbicide,Microbicides,Anti-Microbial Agents,Antiinfective Agents,Antimicrobial Agents,Agent, Anti-Infective,Agent, Anti-Microbial,Agent, Antimicrobial,Agents, Anti-Infective,Agents, Anti-Microbial,Agents, Antiinfective,Agents, Antimicrobial,Anti Infective Agent,Anti Infective Agents,Anti Microbial Agent,Anti Microbial Agents
D001646 Bile An emulsifying agent produced in the LIVER and secreted into the DUODENUM. Its composition includes BILE ACIDS AND SALTS; CHOLESTEROL; and ELECTROLYTES. It aids DIGESTION of fats in the duodenum. Biliary Sludge,Sludge, Biliary
D015363 Quinolones A group of derivatives of naphthyridine carboxylic acid, quinoline carboxylic acid, or NALIDIXIC ACID. Ketoquinoline,Ketoquinolines,Oxoquinoline,Oxoquinolines,Quinolinone,Quinolinones,Quinolone
D015394 Molecular Structure The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds. Structure, Molecular,Molecular Structures,Structures, Molecular

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