Ex Vivo Pharmacokinetic/Pharmacodynamic Integration Model of Cefquinome Against Escherichia coli in Foals

Cefquinome is used to treat septicemia caused by <i>Escherichia coli</i> (<i>E. coli</i>) and respiratory infections caused by <i>Streptococcus equi</i> subsp. <i>zooepidemicus</i> in foals. However, studies reporting the use of cefquinome to target <i>E. coli</i> as pathogens of sepsis are lacking. Therefore, this study aimed to determine the optimal dosage regimen for cefquinome against <i>E. coli</i> using a PK/PD model. After the administration of 1 mg/kg cefquinome (intramuscularly or intravenously), blood samples were collected at different time points to determine the serum concentration of cefquinome via HPLC. The pharmacokinetic parameters were evaluated via NCA (WinNonlin 5.2.1 software). The main pharmacokinetic parameters of cefquinome in foals were as follows: after intravenous administration, the elimination half-life (T_1/2β) was 2.35 h, the area under the curve (AUC_0-last) was 12.33 μg·h/mL, the mean residence time (MRT_0-last) was 2.67 h, and the clearance rate (CL) was 0.09 L/h/kg. After intramuscular administration, the peak concentration (C_max) was 0.89 μg/mL, the time to reach the maximum serum concentration (T_max) was 2.16 h, T_1/2β was 4.16 h, AUC_0-last was 5.41 μg·h/mL, MRT_0-last was 4.92 h, CL was 0.15 L/h/kg, and the absolute bioavailability (F) was 43.86%. An inhibitory sigmoid Emax model was used to integrate the PK/PD indices with ex vivo antimicrobial effects to identify pharmacodynamic targets (PDTs). According to the dose calculation formula, the doses of intramuscularly administered cefquinome required to achieve bacteriostatic effects, bactericidal effects, and bactericidal elimination were 1.10, 1.66, and 2.28 mg/kg, respectively. However, further studies are warranted to verify the therapeutic efficacy of cefquinome in clinical settings.