Abstract |
L-656,575 is a new oxacephem that, based on studies in rhesus monkeys, is expected to have a moderately long half-life in humans. After administration of a 10-mg/kg dose by the intramuscular route to rhesus monkeys, peak serum concentrations of 32-54 micrograms/ml were seen at about 30 minutes, and the half-life was estimated to be 63 minutes. Urinary recovery of administered dose was greater than 94% in 6 hours. In mice given a 20-mg/kg dose by the subcutaneous route, a peak serum concentration of 22.9 microgram/ml was observed at 15 minutes after dosing, and the half-life in serum was about 18 minutes. Urinary recovery of the dose was 59% in 6 hours. In another study in mice, administration of probenecid did not extend the half-life of L-656,575, suggesting that the antibiotic is excreted primarily by glomerular filtration in this species. Binding to human plasma proteins was 30% at drug concentrations from 25-100 micrograms/ml. L-656,575 also was shown to be efficacious in experimental bacteremias due to Gram-positive and Gram-negative pathogens in mice, thus confirming the broad spectrum of activity demonstrated for L-656,575 in vitro.
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Authors | E C Gilfillan, B A Pelak, R A Fromtling, J Bland, S Hadley, H H Gadebusch |
Journal | The Journal of antibiotics
(J Antibiot (Tokyo))
Vol. 41
Issue 8
Pg. 1137-41
(Aug 1988)
ISSN: 0021-8820 [Print] England |
PMID | 3049491
(Publication Type: Comparative Study, Journal Article)
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Chemical References |
- Anti-Bacterial Agents
- Blood Proteins
- Cephalosporins
- L 656575
- Ceftazidime
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Topics |
- Animals
- Anti-Bacterial Agents
(analysis, pharmacokinetics, therapeutic use)
- Bacterial Infections
(drug therapy)
- Blood Proteins
(metabolism)
- Ceftazidime
(pharmacokinetics)
- Cephalosporins
- Dose-Response Relationship, Drug
- Female
- Glomerular Filtration Rate
- Humans
- Macaca mulatta
- Metabolic Clearance Rate
- Mice
- Protein Binding
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