salicylates and eterilate

Ex vivo antiplatelet properties of 2-(p-acetamido-phenoxy)ethyl-o-acetoxybenzoate (etersalate, Daital) and its effects on serum thromboxane A2 (TXA2) levels and prostaglandin I2 (PGI2) generation were studied in human volunteers at two levels of oral dosing. Etersalate inhibited at the lower dosage platelet function and decreased TXA2 levels, but PGI2 generation from rat aortic rings was stimulated when incubated with plasma from etersalate-treated donors. Blood coagulation parameters remained within normal values. It is suggested that etersalate administration could act on platelet arachidonate metabolism at a different level than that of the cyclooxygenase pathway.

Topics: Acetanilides; Anti-Inflammatory Agents, Non-Steroidal; Epoprostenol; Humans; Platelet Aggregation; Salicylates; Thromboxane A2; Thromboxane B2

Topics: Acetanilides; Animals; Anticoagulants; Dipyridamole; Drug Therapy, Combination; Male; Mice; Platelet Aggregation; Salicylates; Thrombosis

Topics: Acetaminophen; Acetanilides; Administration, Oral; Adult; Biotransformation; Female; Humans; Male; Salicylates; Time Factors

Topics: Acetanilides; Animals; Aspirin; Blood Glucose; Diabetes Mellitus, Experimental; Female; Hypoglycemia; Rats; Rats, Inbred Strains; Salicylates

Oral doses of 14C-eterylate were well absorbed by rat and man and excreted mainly in the urine (94% dose by rat in three days and 91% by man in five days). Oral doses to dogs were excreted in similar proportions in both the urine and faeces, although faecal 14C was probably derived in part, from biliary-excreted material. Peak plasma 14C and drug concn. were generally reached between one and three hours after oral doses. In humans, only two metabolites, salicylic acid and 4-acetamido-phenoxyacetic acid, were detected in plasma. The latter was cleared more rapidly than the former and hence plasma salicyclate concn. reached a peak (10.9 and 19.8 micrograms/ml in Subjects 1 and 2, respectively) and initially declined with a half-life of about two-three hours. Plasma 4-acetamidophenoxyacetic acid concn. reached a peak (4.3, 10.0 micrograms/ml, respectively) and declined with a half-life of about one hour. Tissue concn. of 14C were generally greater in dogs than in rats. Highest conc. occurred at three hours in dogs and at one hour in rats. Apart from those in the liver and kidneys, tissue concn. were lower than those in the corresponding plasma. Unchanged drug was not detected in urine or plasma of any species and was rapidly metabolized in human plasma. The major 14C components in human urine were identified as salicyluric acid and 4-acetamidophenoxyacetic acid; minor metabolites were salicylic acid, gentisic acid and paracetamol. These metabolites were also detected in rat urine albeit in different proportions to those in human urine. Dog urine contained less of these metabolites and a major proportion of the 14C was associated with relatively non-polar components. Although salicylic acid and 4-acetamidophenoxyacetic acid were the only major circulating metabolites in man and rat, dog plasma also contained the non-polar urine metabolites.

Topics: Acetanilides; Adult; Animals; Anti-Inflammatory Agents; Biotransformation; Dogs; Humans; Kinetics; Male; Metabolic Clearance Rate; Phenoxyacetates; Rats; Rats, Inbred Strains; Salicylates; Species Specificity; Tissue Distribution

Topics: Acetanilides; Anti-Inflammatory Agents; Aspirin; Humans; In Vitro Techniques; Platelet Aggregation; Salicylates

A comparison was performed of acetylsalicylic acid and two ether derivatives (Benorilate and Eterilate) and indomethacin in order to ascertain the in vivo effects on the lymphoblastic transformation and the primary immune response in mice. The humoral response in Benorilate-and Eterilate-treated mice was 40-50% lower than that of the controls, whereas in acetylsalicylic acid-treated mice the response was only 25% inhibited. The number of immunoglobulin synthesizing cells was neither reduced by acetylsalicylic acid nor by its derivatives, although indomethacin treatments (used for comparative purposes) inhibited by 40% the number of direct plaque-forming cells on the days tested. Mitogen-induced proliferation of spleen lymphocytes was also inhibited in the treated mice; these inhibitions were negligible in the case of cells from acetylsalicylic acid-treated mice activated by concanavalin A and slight in cells from Benorilate-treated mice activated by bacterial lipopolysaccharide. When lymphocytes from drug-treated animals were further cultured in the presence of the same drug, a variable inhibition of mitogen-induced proliferation was observed. These different in vivo effects of acetylsalicylic acid and the two ether derivatives and indomethacin may be due to a distinct action on diverse lymphocyte subpopulations altering their cellular collaborative interactions or modifying the prostaglandin availability.

Topics: Acetanilides; Animals; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Cells, Cultured; Female; Hemagglutinins; Immunity; Immunosuppressive Agents; Indomethacin; Lymphocyte Activation; Mice; Salicylates; Thymidine