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Biomedical subjects

E Greselin

Publications and source records attributed to E Greselin.

25 records · Page 2Linked to original sources
PubMed1977

Clofibrate and clofibric acid: comparison of the metabolic disposition in rats and dogs.

In rats, equimolar oral doses of [14C]clofibrate and [14c]clofibric acid produced essentially the same profiles of blood levels, tissue distribution and excretion of radioactivity. Both compounds were completely absorbed, and all radioactivity found in the serum was due to clofibric acid (CPIB). Tissues contained readily detectable radioactivity levels, but the concentration was generally lower than in serum. A large proportion of CPIB in liver, heart, kidney, fat and muscle was associated with intracellular space. In rat urine, CPIB was present both free and conjugated with glucuronic acid. Approximately 97% of the serum CPIB was not conjugated. Identical decreases in serum lipids and hepatic cholesterol synthesis were observed in rats treated for 1 week with either compound. In dogs, the serum contained 40% more radioactivity after [14C]clofibric acid than after an equimolar oral dose of [14C]clofibrate; approximately 88% of the serum radioactivity was due to CPIB. Some biliary excretion was detected. The extent of binding to serum protein varied with concentration of CPIB and with the species; the affinity was in the order man greater than dog greater than rat. The results demonstrate that clofibric acid and clofibrate are metabolically and pharmacologically equivalent in rats, but not in dogs. The data are in accordance with the view that the pharmacological activity of clofibrate is due to clofibric acid.

Animals↗
PubMed1966

An inhibitor of cholesterol biosynthesis and the alveolar macrophages.

An accumulation of lipid material was observed in the alveolar macrophages of animals treated per os with an inhibitor of cholesterol biosynthesis (trans-1, 4-bis) (2-dichlorobenzyl-aminomethyl) cyclohexane dihydrochloride: AY-9944). This lipid is probably 7-dehydro-cholesterol which is a precursor of cholesterol and accumulates in various organs, especially in the lungs. In the rats and pigs the reaction is limited to the alveolar macrophages which are expectorated or degenerate. In dogs some of the alveolar macrophages are also expectorated while others continue to collect a cholesterol-like lipid until large crystals form, which provoke the formation of giant cells and later fibrocytes, giving rise to "cholesterol granulomata".

Animals↗
PubMedDate not supplied

Metabolic disposition and pharmacokinetics of the aldose reductase inhibitor tolrestat in rats, dogs, and monkeys.

The metabolic disposition and pharmacokinetics of the aldose reductase inhibitor tolrestat were studied in rats, dogs, and assamese and capuchin monkeys. In addition, the ocular penetration of tolrestat was examined in rabbits. The bioavailability of tolrestat was 81% in rats and 68% in dogs. In contrast to rats, a major proportion of the serum 14C in dogs and monkeys was due to unchanged drug. The terminal elimination half-life of tolrestat in serum was 3.5 hr in rats, 11 hr in dogs, and 9 hr in monkeys; in both dogs and monkeys, the total body clearance was 200 ml/kg X hr, and the volume of distribution was 3 liters/kg. In rats and dogs, serum tolrestat concentrations were similar after single and multiple po doses, and were linearly dose-related up to 25 mg/kg, but increased disproportionately at higher doses. Tolrestat was at least 98% bound to rat and dog serum proteins. Except for organs associated with absorption and elimination, tissue 14C levels were lower than in serum of rats and capuchin monkeys, and there was no tissue 14C accumulation. The 14C from topically applied 14C-tolrestat readily penetrated into the eyes of rabbits. Liver microsomal cytochrome P-450 was virtually unaltered in tolrestat-treated rats. Tolrestat (and/or its metabolites) underwent enterohepatic circulation in rats. Most of the 14C from 14C-tolrestat administered po and iv to rats and dogs was excreted in the feces. Based on 14C excretion, the absorption of tolrestat was 84% in rats and 82% in dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Distribution and excretion of furobufen in rats and dogs.

Groups of male rats and dogs were given single doses of 50 mg of 14C-furobufen per kg orally or intravenously. In rats, tissue radioactivity levels were generally lower than that of serum. Radioactivity accumulated in and was retained by white adipose tissue. The radioactivity in fat was due to a conjugate of dibenzofuranacetic acid, the major metabolite of furobufen. Approximately one-half of the dose was excreted each in the urine and feces of rats after oral and intravenous administration of 14C-furobufen. A similar excretion pattern was observed in dogs after an oral dose.

Adipose Tissue↗