Toutain, P. L., Potter, T., 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). pp. 16-27. ISSN 0140-7783

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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.

Item Type:	Article
All Authors:	Toutain, P. L., Potter, T., Pelligand, L., Lacroix, M., Illambas, J., Lees, P.
Additional Information:	ISI Document Delivery No.: EO1MP Times Cited: 2 Cited Reference Count: 36 Toutain, P. -L. Potter, T. Pelligand, L. Lacroix, M. Illambas, J. Lees, P. Zoetis Ltd P. Lees has acted as a consultant to Pfizer Animal Health. He has not consulted for Zoetis, only the predecessor company Pfizer on another drug. L. Pelligand has received funding from Zoetis Ltd for nonrelated studies on maropitant in the dog. None of the other authors has a financial or personal relationship with other people or organizations that could inappropriately influence or bias the contents of the paper. 2 1 WILEY-BLACKWELL HOBOKEN J VET PHARMACOL THER
Uncontrolled Keywords:	LUNG-TISSUE CONCENTRATIONS INTRACELLULAR ACCUMULATION PULMONARY PHARMACOKINETICS SUBCELLULAR-DISTRIBUTION VETERINARY-MEDICINE RESPIRATORY-DISEASE CATTLE MODEL EFFLUX PLASMA
Research teams:	ICR divisions > Clinical Studies > Clinical Trials & Statistics Unit
Depositing User:	Barry Jenkins
Date Deposited:	25 Apr 2017 12:54
Last Modified:	25 Apr 2017 12:54
URI:	http://publications.icr.ac.uk/id/eprint/15790

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