GIRARD D, FINEGAN SM, LAME M; Interscience Conference on Antimicrobial Agents and Chemotherapy (43rd: 2003: Chicago, Ill.).
Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2003 Sep 14-17; 43: abstract no. B-318.
PGRD Groton Laboratories, Pfizer Inc., Groton, CT.
BACKGROUND: The mouse bacterial septicemia model has been used as a primary in vivo screening tool in the discovery of new anti-infective agents since the 1930s. This model has played a significant role in our understanding of anti-infective pharmacology, especially the relationship between pathogen and antibiotic therapy; most recently it has provided guidance, pre-clinically, in establishing PK/PD relationships for anti-infective agents as well as in the planning of initial clinical studies. The PK of amoxicillin and azithromycin were characterized in a Staphylococcus aureus (SA) septicemia model using the virulence-enhancing agents hog gastric mucin (HGM) and Brewers yeast (BY). METHODS: CF-1 female mice were randomly assigned to one of 5 groups: 1) Control, 2) HGM, 3) HGM & SA, 4) BY and 5) BY & SA. Mice received a 0.5 ml intraperitoneal injection of 1) PBS, 2) 10% HGM, 3) 10[6] CFU SA in 10% HGM, 4) 3% BY and 5) 10[6] CFU SA in 3% BY. All groups received a 25 mg/kg oral dose of amoxicillin or azithromycin one hour following IP injection. Plasma levels were determined using an LC/MS or bio-assay and PK parameters were estimated using non-compartmental methods. RESULTS: [table: see text]. CONCLUSION: IP administration of virulence-enhancing agents (HGM and BY) dramatically affect the oral PK of amoxicillin and azithromycin (rate of absorption, plasma exposure and elimination) in the mouse. These data suggest that it is imperative that the pre-clinical PK profile being used to define the PK/PD relationships of an anti-infective be characterized in the identical efficacy model where the PD is being evaluated.
Publication Types:
Keywords:
- Amoxicillin
- Amoxicillin-Potassium Clavulanate Combination
- Animals
- Anti-Infective Agents
- Azithromycin
- Female
- Mice
- Models, Biological
- pathogenicity
- pharmacokinetics
Other ID:
UI: 102264644
From Meeting Abstracts