Premium
Standard PK / PD concepts can be applied to determine a dosage regimen for a macrolide: the case of tulathromycin in the calf
Author(s) -
Toutain P.L.,
Potter T.,
Pelligand L.,
Lacroix M.,
Illambas J.,
Lees P.
Publication year - 2017
Publication title -
journal of veterinary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.527
H-Index - 60
eISSN - 1365-2885
pISSN - 0140-7783
DOI - 10.1111/jvp.12333
Subject(s) - minimum inhibitory concentration , pasteurella multocida , pharmacokinetics , pharmacodynamics , population , regimen , medicine , pharmacology , biology , antibiotics , microbiology and biotechnology , bacteria , genetics , environmental health
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.