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- Title
Pharmacokinetic/pharmacodynamic evaluation of marbofloxacin as a single injection for Pasteurellaceae respiratory infections in cattle using population pharmacokinetics and Monte Carlo simulations.
- Authors
Paulin, A.; Schneider, M.; Dron, F.; Woehrle, F.
- Abstract
Population pharmacokinetic of marbofloxacin was investigated with 52 plasma concentration-time profiles obtained after intramuscular administration of Forcyl® in cattle. Animal's status, pre-ruminant, ruminant, or dairy cow, was retained as a relevant covariate for clearance. Monte Carlo simulations were performed using a stratification by status, and 1000 virtual disposition curves were generated in each bovine subpopulation for the recommended dosage regimen of 10 mg/kg as a single injection. The probability of target attainment ( PTA) of pharmacokinetic/pharmacodynamic ( PK/ PD) ratios associated with clinical efficacy and prevention of resistance was determined in each simulated subpopulation. The cumulative fraction of response ( CFR) of animals achieving a PK/ PD ratio predictive of positive clinical outcome was then calculated for the simulated dosage regimen, taking into account the minimum inhibitory concentration ( MIC) distribution of Pasteurella multocida, Mannheimia haemolytica, and Histophilus somni. When considering a ratio of AUC0-24 hr/ MIC (area under the curve/minimum inhibitory concentration) greater than 125 hr, CFRs ranging from 85% to 100% against the three Pasteurellaceae in each bovine subpopulation were achieved. The PTA of the PK/ PD threshold reflecting the prevention of resistances was greater than 90% up to MPC (mutant prevention concentration) values of 1 μg/ml in pre-ruminants and ruminants and 0.5 μg/ml in dairy cows.
- Subjects
ANTI-infective agents; PHARMACOKINETICS; PHARMACODYNAMICS; PASTEURELLACEAE; TREATMENT of cattle diseases; MONTE Carlo method; VETERINARY medicine
- Publication
Journal of Veterinary Pharmacology & Therapeutics, 2018, Vol 41, Issue 1, p39
- ISSN
0140-7783
- Publication type
Article
- DOI
10.1111/jvp.12418