RESUMEN
Pathophysiological changes involved in drug disposition in critically ill patients should be considered in order to optimize the dosing of vancomycin administered by continuous infusion, and certain strategies must be applied to reach therapeutic targets on the first day of treatment. The aim of this study was to develop a population pharmacokinetic model of vancomycin to determine clinical covariates, including mechanical ventilation, that influence the wide variability of this antimicrobial. Plasma vancomycin concentrations from 54 critically ill patients were analyzed simultaneously by a population pharmacokinetic approach. A nomogram for dosing recommendations was developed and was internally evaluated through stochastic simulations. The plasma vancomycin concentration-versus-time data were best described by a one-compartment open model with exponential interindividual variability associated with vancomycin clearance and the volume of distribution. Residual error followed a homoscedastic trend. Creatinine clearance and body weight significantly dropped the objective function value, showing their influence on vancomycin clearance and the volume of distribution, respectively. Characterization based on the presence of mechanical ventilation demonstrated a 20% decrease in vancomycin clearance. External validation (n = 18) was performed to evaluate the predictive ability of the model; median bias and precision values were 0.7 mg/liter (95% confidence interval [CI], -0.4, 1.7) and 5.9 mg/liter (95% CI, 5.4, 6.4), respectively. A population pharmacokinetic model was developed for the administration of vancomycin by continuous infusion to critically ill patients, demonstrating the influence of creatinine clearance and mechanical ventilation on vancomycin clearance, as well as the implications for targeting dosing rates to reach the therapeutic range (20 to 30 mg/liter).
Asunto(s)
Antibacterianos/farmacocinética , Antibacterianos/uso terapéutico , Creatinina/metabolismo , Enfermedad Crítica/terapia , Respiración Artificial , Vancomicina , Anciano , Monitoreo de Drogas , Femenino , Humanos , Infusiones Intravenosas , Unidades de Cuidados Intensivos , Masculino , Nomogramas , Vancomicina/sangre , Vancomicina/farmacocinética , Vancomicina/uso terapéuticoAsunto(s)
Antidepresivos/efectos adversos , Síndrome de QT Prolongado/inducido químicamente , Clorhidrato de Venlafaxina/efectos adversos , Síndrome Coronario Agudo/diagnóstico , Síndrome Coronario Agudo/tratamiento farmacológico , Adulto , Fármacos Cardiovasculares/uso terapéutico , Errores Diagnósticos , Sustitución de Medicamentos , Electrocardiografía , Humanos , Síndrome de QT Prolongado/diagnóstico , Masculino , Sertralina/uso terapéutico , Bloqueadores de los Canales de Sodio/efectos adversos , Taquicardia Sinusal/inducido químicamente , Taquicardia Sinusal/diagnóstico , Taquicardia Sinusal/tratamiento farmacológicoRESUMEN
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