Pharmacokinetics Study and Modelling of Amoxicillin After Intramuscular Administration in Veal Calves Suffering From
Morgane Moustaghfir1, Bernadette Espana2, Karine Hauray3
1ANSES-Université de Lyon, Unité Antibiorésistance et Virulence Bactériennes, Lyon, France.
Abstract:
The objective of this study was to estimate plasma pharmacokinetic parameters for amoxicillin (AMX) in calves (n = 7) suffering from omphalitis after a single intramuscular (IM) administration of 8.75 mg/kg of amoxicillin and clavulanic acid (AMC) (7 mg/kg of AMX and 1.75 mg/kg of clavulanic acid). Plasma samples were collected over 6 h. AMX concentrations were measured via liquid chromatography/mass spectrometry (LC-MS/MS). A non-compartmental analysis was first used to determine pharmacokinetic parameters; then a population pharmacokinetic and a Monte Carlo simulation were performed on a hypothetical herd of 1000 calves. After a single IM administration, we observed a correlation between Cl and Vd and a high variability of PK parameters among individuals. Maximum plasma concentration was between 1.22 and 5.99 μg/mL and Tmax was between 0.75 and 2 h. The plasma concentration values of AMX fit to a one-compartment model with linear elimination and administration by extravascular route with a zero-order process (duration Tk0) with a lag time (Tlag). Results showed that the plasma concentration never reached 4 mg/L, which is the breakpoint of AMX-susceptible Escherichia coli or Pasteurella spp. isolates, even after simulation of repeated administration.
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