Pharmacokinetic/Pharmacodynamic Modelling of Cefquinome in Lactating Sheep and Lactating Goats After Intravenous, Subcutaneous and Long-Acting Administrations

Abstract

The pharmacokinetics (PK) and pharmacokinetic-pharmacodynamic (PK/PD) relationships of cefquinome in small ruminants remain incompletely characterized, particularly for long-acting (LA) formulations. This study evaluated cefquinome disposition after intravenous (IV), subcutaneous (SC) and LA subcutaneous (SC-LA) administration in lactating sheep and goats using nonlinear mixed-effects models (NLMEs) and Monte Carlo (MC) simulations. Cefquinome exhibited low volumes of distribution (0.21-0.31 L/kg), with goats showing higher clearance and shorter terminal half-lives than sheep. The SC-LA formulation reduced the absorption rate constant and increased both the mean absorption time and terminal half-life by 4-6-fold, resulting in sustained systemic exposure over 48 h. PK/PD analysis showed higher PK/PD cut-off values for the LA formulation, with values of 0.125 ?g/mL for the fT > MIC index and 0.25 ?g/mL for the fAUC/MIC index, respectively, whereas IV and SC regimens achieved lower thresholds. MC simulations indicated that only the LA formulation achieved ? 90% probability of target attainment (PTA) values at MICs equivalent to tentative epidemiological cut-off values (TECOFF) for respiratory pathogens. Notably, fAUC/MIC provided a more informative descriptor of efficacy for the LA formulation. These findings highlight the advantage of LA formulations and demonstrate improved performance compared with conventional dosing regimens in sheep and goats.