INSTITUTO DE INVESTIGACIONES EN RECURSOS NATURALES Y SUSTENTABILIDAD JOSE SANCHEZ LABRADOR S.J.
Unidad Ejecutora - UE
congresos y reuniones científicas
Context sensitive pharmacokinetics of cephalothin after intravenous administration in anesthetized dogs undergoing ovariohysterectomy by nonlinear mixed-effect modelling analysis
ZARAZAGA MARÍA DEL PILAR; HIMELFARB MARTÍN ALEJANDRO; SAN ANDRÉS MANUEL IGNACIO; LORENZUTTI AUGUSTO MATÍAS; TINTI MARIANO GUILLERMO; SERRANO-RODRÍGUEZ JUAN MANUEL; LITTERIO NICOLÁS JAVIER; RUBIO-LANGRE SONIA
Congreso; Ninth International Conference on Antimicrobial Agents in Veterinary Medicine (AAVM); 2018
Department of Health, Animal Science and Food Safety (VESPA)
Cephalothin (CPH) is a first generation cephalosporin indicated for antimicrobial prophylaxis of non-contaminated surgery. The recommended dose regimens are based on pharmacokinetic data obtained from awake animals, in which anesthesia or surgery effects are not present. Since CPH is eliminated by renal excretion, and it is known that anesthesia and surgery could affect the cardiac output, renal blood flow and glomerular filtration rate, pharmacokinetics of CPH may be context-sensitive when these factors are present. Sixteen healthy female dogs were included in the study. Six dogs were randomly assigned to a pharmacokinetic study of CPH by IV route without anesthesia and surgery. Moreover, the other ten dogs undergoing ovariohysterectomy, with anesthetic risk ASA I, were included in the pharmacokinetic study of CPH after IV administration under anesthesia and surgery conditions. CPH was administered IV at a dose of 25 mg/kg in both pharmacokinetic studies. Blood samples were collected at different time points until 12h. All animals finished the study and surgery without complications. CPH quantification in serum samples was determined by high performance liquid chromatography with UV detector (HPLC/uv). Concentration vs. time data was analyzed with a nonlinear mixed-effect modelling using Monolix (Lixoft, Batiment D, Antony, France), using the Stochastic Approximation Expectation-Maximization (SAEM) algorithm. A bi-compartmental pharmacokinetic model with a combined error model was selected. The pharmacokinetic parameters estimated by the model were Cl (clearance of the central compartment), V1 (volume of distribution of central compartment), Q (inter-compartmental clearance) and V2 (volume of distribution of peripheral compartment). The following covariates were included in the model to evaluate its effect on pharmacokinetics of CPH: age, weight and anesthesia/surgery conditions. The covariates were included in the model if showed statistical significance (pMIC is the main PK/PD parameter to assess antimicrobial efficacy.