The Pharmacology of Duomycin

Abstract

UOMYCIN,* aureomycin A-377, is a yellow crystalline antibiotic [ 182 1 * Trade mark Harned et al.: Pharmacology 183 per kg.;(d) at one hour and at two hours, the dogs were catheterized and the bladders washed with 0.9 per cent sodium chloride; (e) the specimens were alkalinized and the amount of dye determined with a photoelectric colorimeter (filter No. 540). Normal dogs excreted from 60 to 85 per cent during the first hour.Liver function was estimated by injecting intravenously 5 mg. per kg. of bromsulphalein. Blood w&s drawn at 5 and 30 minutes subsequent to the dose and the amount of the dye retained in the serum was estimated with a photoelectric colorimeter (filter No. 560). Normal retention at thirty minutes was from 0 to 15 per cent.Tests for histaminic action were made on isolated guinea pig gut and also by following the changes in blood pressure in anesthetized cats. Antihistaminic action was tested on the isolated guinea pig gut and on guinea pigs in 8. spray chamber.Tests for antipyretic action were made by following the rectal temperatures of rabbits injected intravenously with 0.25 cc. per kg. of typhoid vaccine, and of rats injected subcutaneously with 10 cc. per kg. of a 15 per cent suspension of yeasks Tests for irritation were made by the intracutaneous injection into the guinea pig skin and by local application to the conjunctival sac of the rabbit eye. In the eye, three or six drops at five minute intervals were used. Blood, urine and cerebrospinal fluid levels of duomycin were estimated biologically against Bacillus subtilis using a four hour period.6Duomycin is soluble in acid and in alkaline solutions, but is almost insoluble at pH 7. Four per cent solutions may be easily prepared as the hydrochloride pH 2.5 or as a sodium salt in a carbonate buffer pH 8.5.At pH 2.5, the salt is stable but at pH 8.5,25" C., it loses 12 per cent of its activity in 30 minutes, 20 per cent in 1 hour, and 40 per cent in 2 hours. Duomycin was administered parenterally usually as a 1 or 2 per cent solution pH 2.5 or pH 8.5. The hydrochloride was always used for the oral doses unless a different form was specified.Acute Toxicity Single Doses, Unanesthetized Animals. Orally, the toxicity is of a lorn order. Mice tolerated 1500 mg. per kg. and rats, 3000 mg. per kg. At 2500 mg. per kg., the mouse-mortality was 5 per cent (TABLE 1). No attempt was made to determine the maximal tolerated dose in larger animals. Intravenously, the L.D.50 for the hydrochloride was 134 mg. per kg. for mice and 118 mg. per kg. for rats (FIGURE 1). The alFline form appeared to be a little more toxic in mice but less toxic in rats (TABLE 1). These differences, however, are not significant. Three unanesthetized dogs readily tolerated intravenously, doses of 50 mg. per kg., pH 2.5,* given at a rate of 10 mg. per kg. per minute. Some days later, this dose in Doaes larger than SO m . per kg. of duomycin hydrochloride pH 4.5 produce hemoglobinuria. An e urvalrnt quantity of hykochloric acid will produce the same result. Hemoglohinuria has nevce ...

Calcification of the Peritoneum

“…Bryer et al (1948), working with dogs, failed to detect any measurable amounts in the spinal fluid after parenteral administration. However, Harned et al (1948) found that intravenous administration in dogs resulted in levels up to 0.8 ,ug. per ml.…”

Diethylcarbamazine: A Leukotriene Inhibitor

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Further Experiences With Intravenous Aùreomycin Therapy. A Study of 116 Cases 12

“…vials. The procedures for preparing and administering the antibiotic followed in this study have (4) found that the antibiotic is stable in an acid medium and loses potency in an alkaline environment.…”