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Pharmacokinetic–pharmacodynamic integration and modelling of oxytetracycline for the calf pathogens Mannheimia haemolytica and Pasteurella multocida

Lees, P; Potter, T; Pelligand, L; Toutain, P L

Authors

P Lees

T Potter

L Pelligand

P L Toutain



Abstract

A calf tissue cage model was used to study the pharmacokinetics (PK) and pharmacodynamics (PD) of oxytetracycline in serum, inflamed (exudate) and noninflamed (transudate) tissue cage fluids. After intramuscular administration, the PK was characterized by a long mean residence time of 28.3 hr. Based on minimum inhibitory concentrations (MICs) for six isolates each of Mannheimia haemolytica and Pasteurella multocida, measured in serum, integration of in vivo PK and in vitro PD data established area under serum concentration–time curve (AUC0–∞)/MIC ratios of 30.0 and 24.3 hr for M. haemolytica and P. multocida, respectively. Corresponding AUC0–∞/MIC ratios based on MICs in broth were 656 and 745 hr, respectively. PK-PD modelling of in vitro bacterial time–kill curves for oxytetracycline in serum established mean AUC0–24 hr/MIC ratios for 3log10 decrease in bacterial count of 27.5 hr (M. haemolytica) and 60.9 hr (P. multocida). Monte Carlo simulations predicted target attainment rate (TAR) dosages. Based on the potency of oxytetracycline in serum, the predicted 50% TAR single doses required to achieve a bacteriostatic action covering 48-hr periods were 197 mg/kg (M. haemolytica) and 314 mg/kg (P. multocida), respectively, against susceptible populations. Dosages based on the potency of oxytetracycline in broth were 25- and 27-fold lower (7.8 and 11.5 mg/kg) for M. haemolytica and P. multocida, respectively.

Citation

Lees, P., Potter, T., Pelligand, L., & Toutain, P. L. (2018). Pharmacokinetic–pharmacodynamic integration and modelling of oxytetracycline for the calf pathogens Mannheimia haemolytica and Pasteurella multocida. Journal of Veterinary Pharmacology and Therapeutics, 41(1), 28-38. https://doi.org/10.1111/jvp.12439

Journal Article Type Article
Acceptance Date Jun 12, 2017
Publication Date Feb 1, 2018
Deposit Date Nov 10, 2017
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 41
Issue 1
Pages 28-38
DOI https://doi.org/10.1111/jvp.12439
Public URL https://rvc-repository.worktribe.com/output/1388909

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