Pharmacokinetics Study and Modelling of Amoxicillin After Intramuscular Administration in Veal Calves Suffering From Omphalitis

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 V_d and a high variability of PK parameters among individuals. Maximum plasma concentration was between 1.22 and 5.99 μg/mL and T_max 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.