P Lees
Pharmacokinetic/pharmacodynamic integration and modelling of amoxicillin for the calf pathogens Mannheimia haemolytica and Pasteurella multocida
Lees, P; Pelligand, L; Illambas, J; Potter, T J; Lacroix, M; Rycroft, A N; Toutain, P L
Authors
L Pelligand
J Illambas
T J Potter
M Lacroix
A N Rycroft
P L Toutain
Abstract
The antimicrobial properties of amoxicillin were determined for the bovine respiratory tract pathogens, Mannheima haemolytica and Pasteurella multocida. Minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and time‐kill curves were established. Pharmacokinetic (PK)/pharmacodynamic (PD) modelling of the time‐kill data, based on the sigmoidal Emax equation, generated parameters for three levels of efficacy, namely bacteriostatic, bactericidal (3log10 reduction) and 4log10 reduction in bacterial counts. For these levels, mean AUC(0–24 h)/MIC serum values for M. haemolytica were 29.1, 57.3 and 71.5 h, respectively, and corresponding values for P. multocida were 28.1, 44.9 and 59.5 h. Amoxicillin PK was determined in calf serum, inflamed (exudate) and noninflamed (transudate) tissue cage fluids, after intramuscular administration of a depot formulation at a dosage of 15 mg/kg. Mean residence times were 16.5 (serum), 29.6 (exudate) and 29.0 h (transudate). Based on serum MICs, integration of in vivo PK and in vitro PD data established maximum concentration (Cmax)/MIC ratios of 13.9:1 and 25.2:1, area under concentration–time curve (AUC0–∞)/MIC ratios of 179 and 325 h and T>MIC of 40.3 and 57.6 h for P. multocida and M. haemolytica, respectively. Monte Carlo simulations for a 90% target attainment rate predicted single dose to achieve bacteriostatic and bactericidal actions over 48 h of 17.7 and 28.3 mg/kg (M. haemolytica) and 17.7 and 34.9 mg/kg (P. multocida).
Citation
Lees, P., Pelligand, L., Illambas, J., Potter, T. J., Lacroix, M., Rycroft, A. N., & Toutain, P. L. (in press). Pharmacokinetic/pharmacodynamic integration and modelling of amoxicillin for the calf pathogens Mannheimia haemolytica and Pasteurella multocida. Journal of Veterinary Pharmacology and Therapeutics, 38(5), 457-70. https://doi.org/10.1111/jvp.12207
Journal Article Type | Article |
---|---|
Acceptance Date | Jan 7, 2015 |
Deposit Date | Feb 13, 2016 |
Journal | Journal of Veterinary Pharmacology and Therapeutics |
Print ISSN | 0140-7783 |
Electronic ISSN | 1365-2885 |
Publisher | American Academy of Veterinary Pharmacology and Therapeutics |
Peer Reviewed | Peer Reviewed |
Volume | 38 |
Issue | 5 |
Pages | 457-70 |
DOI | https://doi.org/10.1111/jvp.12207 |
Public URL | https://rvc-repository.worktribe.com/output/1402315 |
Additional Information | Corporate Creators : Ecole Nationale Veterinaire De Toulouse |
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