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This study was performed in 145 pigs to develop a population pharmacokinetics (PPK) model by i.m. administration of cefquinome (CEQ) at the dose of 2 mg/kg in the neck muscle. Serum physiological and biochemical parameters for each pig were determined before administration. After administration, 2–4 samples were collected at random, with the sampling point evenly distributed in the three periods (<1 h, 1–4 h and >4 h). The plasma concentration of CEQ was determined by high performance liquid chromatography with UV detector. The pharmacostatistical analyses of concentration-time data, weight, age, gender, serum physiological and biochemical parameters were performed with nonlinear mixed effect modeling (NONMEM). A one-compartmental model with first-order absorption and elimination adequately described the data from the study group. The optimal random effect model of pharmacokinetics parameters was of log-normal distribution and the residual errors assumed a mixed-type model (proportional and additive) to best explain intra-individual variability. Covariate analysis showed that body weight is positively correlated with apparent volume of distribution (V/F) and body clearance (CL/F). The typical PPK parameters of Ka, CL, and V were 0.564/h, 5.15 L/h, and 1.36 L, respectively.