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Standard PK/PD concepts can be applied to determine a dosage regimen for a macrolide: the case of tulathromycin in the calf

Toutain, P L; Potter, T J; Pelligand, L; Lacroix, M; Illambas, J; Lees, P

Authors

P L Toutain

T J Potter

L Pelligand

M Lacroix

J Illambas

P Lees



Abstract

The pharmacokinetic (PK) profile of tulathromycin, administered to calves subcutaneously at the dosage of 2.5 mg/kg, was established in serum, inflamed (exudate), and noninflamed (transudate) fluids in a tissue cage model. The PK profile of tulathromycin was also established in pneumonic calves. For Mannheimia haemolytica and Pasteurella multocida, tulathromycin minimum inhibitory concentrations (MIC) were approximately 50 times lower in calf serum than in Mueller–Hinton broth. The breakpoint value of the PK/pharmacodynamic (PD) index (AUC(0–24 h)/MIC) to achieve a bactericidal effect was estimated from in vitro time‐kill studies to be approximately 24 h for M. haemolytica and P. multocida. A population model was developed from healthy and pneumonic calves and, using Monte Carlo simulations, PK/PD cutoffs required for the development of antimicrobial susceptibility testing (AST) were determined. The population distributions of tulathromycin doses were established by Monte Carlo computation (MCC). The computation predicted a target attainment rate (TAR) for a tulathromycin dosage of 2.5 mg/kg of 66% for M. haemolytica and 87% for P. multocida. The findings indicate that free tulathromycin concentrations in serum suffice to explain the efficacy of single‐dose tulathromycin in clinical use, and that a dosage regimen can be computed for tulathromycin using classical PK/PD concepts.

Citation

Toutain, P. L., Potter, T. J., Pelligand, L., Lacroix, M., Illambas, J., & Lees, P. (2017). Standard PK/PD concepts can be applied to determine a dosage regimen for a macrolide: the case of tulathromycin in the calf. Journal of Veterinary Pharmacology and Therapeutics, 40(1), 16-27. https://doi.org/10.1111/jvp.12333

Journal Article Type Article
Acceptance Date May 8, 2016
Publication Date Jan 1, 2017
Deposit Date Aug 11, 2016
Publicly Available Date Aug 11, 2016
Journal JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS
Print ISSN 0140-7783
Publisher American Academy of Veterinary Pharmacology and Therapeutics
Peer Reviewed Peer Reviewed
Volume 40
Issue 1
Pages 16-27
DOI https://doi.org/10.1111/jvp.12333
Public URL https://rvc-repository.worktribe.com/output/1394240

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