[General pharmacology of T-2588, a new oral cephem antibiotic].
A new oral cephem antibiotic, T-2588, the pivaloyloxymethyl ester of (+)-(6R, 7R)-7-[(Z)-2-(2-amino-4-thiazolyl)-2-methoxyiminoacetamido]-3- [(5-methyl-2H-tetrazol-2-yl)methyl]-8-oxo-5-thia-1-azabicyclo[4.2. 0]oct-2-ene-2-carboxylic acid (T-2525), is mainly absorbed from the intestinal tract and biotransformed to T-2525 thereafter. General pharmacological activities of T-2588 were studied and following results were obtained. On the central nervous system, T-2588 did not show any effects at oral doses of 500-2,000 mg/kg and T-2525 produced only a slight elevation of body temperature in rabbits without any other effects at an intravenous dose of 500 mg/kg. On the respiratory and cardiovascular systems, T-2525 caused a slight hypotension and increased both respiratory rate and femoral blood flow, but no changes were observed in heart rate and electrocardiogram in dogs at an intravenous dose of 500 mg/kg. The T-2525 exerted no significant influence on blood pressure response to isoproterenol, acetylcholine or histamine, but showed a slight tendency to decrease pressor response to adrenaline in dogs at intravenous doses of 100-500 mg/kg. For the renal function in rats, T-2588 had no effects on urine volume, electrolytes and PSP excretion at oral doses of 500-2,000 mg/kg. Intravenous administration of T-2525 caused an increase of sodium excretion at 500 mg/kg and dose-dependent increases of PSP excretion at 20-500 mg/kg. Hematological studies revealed that both T-2588 at oral doses of 500-2,000 mg/kg and T-2525 at intravenous doses of 100-500 mg/kg had no effects on bleeding time in mice, blood coagulation and platelet aggregation in rats. The T-2588 exerted no effect on the gastrointestinal system in rats or mice and had no antiinflammatory activity in rats at oral doses of 500-2,000 mg/kg. The T-2525 scarcely affected the motilities of isolated smooth muscle preparations in experimental animals including stomach, ileum, colon, uterus, vas deferens and trachea at a concentration as high as 10(-3) g/ml. The T-2525 increased bile secretion in rats at intravenous doses of 100-500 mg/kg. The T-2525 slightly decreased the twitch tension of musculus gastrocnemius induced by electrical stimulation in rats at an intravenous dose of 500 mg/kg. These results indicate that T-2588 is a pharmacologically inactive antibiotic.
D000818:Animals; D001341:Autonomic Nervous System / Q000187:drug effects; D001769:Blood / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects; D002415:Cats; D015281:Cefmenoxime / Q000031:analogs & derivatives*; D002490:Central Nervous System / Q000187:drug effects; D002511:Cephalosporins / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009130:Muscle, Smooth / Q000187:drug effects; D011247:Pregnancy; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D012137:Respiratory System / Q000187:drug effects; D013045:Species Specificity
D002511:Cephalosporins; C046817:cefteram pivoxil; D015281:Cefmenoxime