BIOLOGICAL ACTIVITY OF MEGALOMICIN A PHOSPHATE, A WATER-SOLUBLE SALT OF MEGALOMICIN A

Abstract

Megalomicin A phosphate is a new, stable, water-soluble salt of the new Micromonospora-produced macrolide antibiotic megalomicin A. The studies reported here suggest that the phosphate salt has the same spectrum of activity and in vitro potency as the insoluble base. Of particular interest is the substantial degree of activity seen against several gram-negative bacteria in comparisonto that usually seen with other macrolides. Mouseprotection tests suggest that the salt is morepotent than the base whengiven subcutaneously, but this is undoubtedly due to the greater availability of drug when given in its soluble form. Solutions of megalomicin A phosphate were well tolerated intramuscularly by monkeys, dogs, cows and rats. Compared to commercially available forms of lincomycin, erythromycin and oleandomycin in dogs, megalomicin A phosphate produces serum levels with equal or greater peak values and significantly prolonged duration. The prolonged duration of serum levels was also seen with megalomicinAbase as reported in earlier studies. Initial tolerance and toxicity tests in dogs and rats suggest that megalomicin A phosphate will be safe and well tolerated. This antibiotic preparation shows promise as a newinjectable antibiotic in manand also for use in the treatment of diseases of veterinary importance.