The disposition and metabolism of meropenem in laboratory animals and man. 1989

M P Harrison, and S R Moss, and A Featherstone, and A G Fowkes, and A M Sanders, and D E Case
Drug Kinetics Group, ICI Pharmaceuticals, Macclesfield, Cheshire, UK.

The disposition and metabolism of meropenem were studied in rats, dogs and cynomolgus monkeys following intravenous administration of [14C]-meropenem, and also in man following intravenous infusion of meropenem. Following intravenous administration to rats and dogs, radioactive material was very rapidly and widely distributed in the tissues, with highest levels detected in the kidney and other highly perfused organs. Concentrations in all tissues decreased rapidly with time. The plasma elimination half-life of meropenem was approximately 6 min in rats, 30 min in monkeys, 45 min in dogs and 1h in man. In all species 90-100% of the dose was excreted via the urine within 24 h. Analysis of the radioactive material in urine from animal studies showed that the major components were unchanged compound (36-43%) and a metabolite corresponding to a beta-lactam ring-opened form (34-51%). In man, approximately 65% of the dose was excreted in urine as unchanged meropenem and most of the remainder as the ring-opened metabolite. As part of the preclinical safety evaluation programme of meropenem, the distribution, metabolism and excretion of [14C]-meropenem were studied in the rat, dog and cynomolgus monkey after single intravenous administration at dose levels corresponding to the lower doses used in toxicity studies. In addition, the metabolism and pharmacokinetics of meropenem in human volunteers were studied.

UI MeSH Term Description Entries
D008252 Macaca fascicularis A species of the genus MACACA which typically lives near the coast in tidal creeks and mangrove swamps primarily on the islands of the Malay peninsula. Burmese Long-Tailed Macaque,Crab-Eating Monkey,Cynomolgus Monkey,M. f. aurea,M. fascicularis,Macaca fascicularis aurea,Monkey, Crab-Eating,Monkey, Cynomolgus,Crab-Eating Macaque,Burmese Long Tailed Macaque,Crab Eating Macaque,Crab Eating Monkey,Crab-Eating Macaques,Crab-Eating Monkeys,Cynomolgus Monkeys,Long-Tailed Macaque, Burmese,Macaque, Burmese Long-Tailed,Macaque, Crab-Eating,Monkey, Crab Eating
D011247 Pregnancy The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH. Gestation,Pregnancies
D011919 Rats, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding. August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D002851 Chromatography, High Pressure Liquid Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed. Chromatography, High Performance Liquid,Chromatography, High Speed Liquid,Chromatography, Liquid, High Pressure,HPLC,High Performance Liquid Chromatography,High-Performance Liquid Chromatography,UPLC,Ultra Performance Liquid Chromatography,Chromatography, High-Performance Liquid,High-Performance Liquid Chromatographies,Liquid Chromatography, High-Performance
D004285 Dogs The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065) Canis familiaris,Dog
D005243 Feces Excrement from the INTESTINES, containing unabsorbed solids, waste products, secretions, and BACTERIA of the DIGESTIVE SYSTEM.
D005260 Female Females
D006207 Half-Life The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. Halflife,Half Life,Half-Lifes,Halflifes
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000077731 Meropenem A thienamycin derivative antibacterial agent that is more stable to renal dehydropeptidase I than IMIPENEM, but does not need to be given with an enzyme inhibitor such as CILASTATIN. It is used in the treatment of bacterial infections, including infections in immunocompromised patients. 3-(5-Dimethylcarbamoylpyrrolidin-3-ylthio)-6-(1-hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo(3.2.0)hept-2-ene-2-carboxylic acid,Merrem,Penem,Ronem,SM 7338,SM-7338,SM7338

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