MICROBIOLOGICAL AND PHARMACOKINETIC STUDIES OF ACYL DEMYCINOSYLTYLOSIN AND RELATED TYLOSIN DERIVATIVES

A series of tylosins and acyl derivatives of 23-O-demycinosyltylosin (DMT) were initially tested for in vitro antibacterial activity and serum levels in squirrel monkeys (po) and mice (iv). Overall, the DMT compounds were more active in vitro than the tylosins. Two tetraacylated DMTs, Sch 37644 and...

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Bibliographic Details
Published in:Journal of antibiotics 1990/09/25, Vol.43(9), pp.1131-1136
Main Authors: CACCIAPUOTI, A. F., LOEBENBERG, D., MOSS, E. L., MENZEL, F. W., RUDEEN, J. A., NAPLES, L. R., CRAMER, C. L., HARE, R. S., MALLAMS, A. K., MILLER, G. H.
Format: Article
Language:English
Subjects:
Animals
Antibacterial agents
Antibiotics. Antiinfectious agents. Antiparasitic agents
Biological and medical sciences
Clarithromycin
Erythromycin - analogs & derivatives
Erythromycin - pharmacokinetics
Erythromycin - pharmacology
Male
Medical sciences
Mice
Molecular Structure
Pharmacology. Drug treatments
Saimiri
Staphylococcal Infections - prevention & control
Staphylococcus - drug effects
Streptococcal Infections - prevention & control
Streptococcus - drug effects
Tylosin - analogs & derivatives
Tylosin - pharmacokinetics
Tylosin - pharmacology
Tylosin - therapeutic use
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Summary:A series of tylosins and acyl derivatives of 23-O-demycinosyltylosin (DMT) were initially tested for in vitro antibacterial activity and serum levels in squirrel monkeys (po) and mice (iv). Overall, the DMT compounds were more active in vitro than the tylosins. Two tetraacylated DMTs, Sch 37644 and Sch 38646, were selected from the initial studies for further evaluation and compared to erythromycin and A-56268 (6-O-methyl erythromycin). Sch 37644 and Sch 38646 were 2 to 8-fold less potent in vitro against Gram-positive bacteria than erythromycin and A-56268. In squirrel monkeys, Sch 37644 (AUC, 19.7 μg•hour/ml) and A-56268 (21.6 μg•hour/ml) had similar serum levels following po administration of 20 mg/kg, while Sch 38646 (11.8 μg•hour/ml) and erythromycin (1.5 μg•hour/ml) had lower levels. In mice administered 200mg/kg orally, Sch 37644 (AUC, 19.4 μg•hour/ml) and Sch 38646 (15.4 μg•hour/ml) had higher serum levels than erythromycin (5.7 μg•hour/ml). A-56268 was the most active po macrolide in mouse protection studies (PD50s) against Staphylococci and Streptococci, while Sch 37644 and Sch 38646 were similar to erythromycin.
ISSN:0021-8820
1881-1469
DOI:10.7164/antibiotics.43.1131