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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

P Lees

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
Publicly Available Date Mar 29, 2024
Journal JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS
Print ISSN 0140-7783
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