Farmacocinética poblacional en el manejo empírico de infecciones en pacientes con neoplasias hematológicas y neutropenia febril pos-quimioterapia

dc.contributorSaavedra Trujillo, Carlos Humberto
dc.contributorDíaz Rojas, Jorge Augusto
dc.contributorGrupo de Investigacion en Enfermedades Infecciosas
dc.creatorParra González, Daniel Sebastián
dc.date.accessioned2022-02-03T20:46:25Z
dc.date.available2022-02-03T20:46:25Z
dc.date.created2022-02-03T20:46:25Z
dc.date.issued2021
dc.identifierhttps://repositorio.unal.edu.co/handle/unal/80871
dc.identifierUniversidad Nacional de Colombia
dc.identifierRepositorio Institucional Universidad Nacional de Colombia
dc.identifierhttps://repositorio.unal.edu.co/
dc.description.abstractLos pacientes con neoplasias hematológicas y neutropenia febril postquimioterapia podrían presentar alteraciones fisiológicas que lleven a cambios en la farmacocinética (PK) de los fármacos comparado a individuos sin cáncer o neutropenia. Estos cambios, en la PK de antibióticos, podrían resultar en fallos terapéuticos y esto a su vez en hospitalizaciones prolongadas, empeoramiento en la severidad de la infección e inclusive en la muerte. En este estudio, se desarrollaron modelos de PK poblacional para cefepime (FEP) y vancomicina (VAN) en el tratamiento empírico de infecciones en pacientes con neutropenia post-quimioterapia. La farmacocinética de FEP fue descrita por un modelo de dos compartimentos con aclaramiento dependiente del nivel de creatinina sérica (SCR), variabilidad interindividual en todos los parámetros y variabilidad residual con una función aditiva. Por otra parte, la farmacocinética de VAN fue descrita con un modelo de dos compartimentos con aclaramiento dependiente del aclaramiento renal de creatinina (ClCr), variabilidad interindividual en todos los parámetros, correlación entre los parámetros V1 y V2 y una variabilidad residual con funciones aditivas dependientes del método de determinación de VAN. Mediante simulaciones de Monte Carlo se encontró que para FEP, el alcance de los objetivos PK/PD (60%fT>MIC y 100%fT>MIC) es muy dependiente de la duración de infusión, así como del efecto de SCR. Para VAN se encuentra que el alcance del indicador AUC/MIC ≥ 400 se ve afectado por cambios en la dosis diaria total y la prolongación de la duración de infusión no afecta el PTA. Se realizó una comparación entre objetivos dependientes de AUC vs Cmin, y se encuentró que el último no es un predictor adecuado del primero. (Texto tomado de la fuente).
dc.description.abstractPatients with haematological malignancies and post-chemotherapy febrile neutropenia may present with physiological alterations that could lead to changes in the pharmacokinetics (PK) of drugs compared to individuals without cancer or neutropenia. These changes, in the PK of antibiotics, could result in therapeutic failures and this in turn in prolonged hospitalizations, worsening the severity of infection and even death. In this study, population PK models were developed for cefepime (FEP) and vancomycin (VAN) in the empirical treatment of infections in patients with post-chemotherapy neutropenia. FEP pharmacokinetics was described by a two-compartment model with clearance dependent on serum creatinine level (SCR), interindividual variability in all parameters, and residual variability with an additive function. On the other hand, the PK of VAN was described with a two-compartment model with clearance dependent on renal creatinine clearance (CrCl), interindividual variability in all parameters, correlation between parameters V1 and V2, and a residual variability with additive functions dependent on the VAN determination method. Through Monte Carlo simulations, it was found that the achievement of PK/PD objectives (60%fT>MIC and 100%fT>MIC) for FEP is highly dependent on the duration of the infusion, as well as the effect of SCR. It was found that the achievement of the PK/PD objective AUC/MIC ≥ 400 with VAN was affected by changes in the total daily dose and the prolongation of the duration of the infusion does not affect the PTA. A comparison was made between targets relying on AUC or Cmin, and it was found that the latter is not an adequate predictor of the former.
dc.languagespa
dc.publisherUniversidad Nacional de Colombia
dc.publisherBogotá - Ciencias - Maestría en Ciencias - Farmacología
dc.publisherDepartamento de Farmacia
dc.publisherFacultad de Ciencias
dc.publisherBogotá, Colombia
dc.publisherUniversidad Nacional de Colombia - Sede Bogotá
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dc.rightsReconocimiento 4.0 Internacional
dc.rightshttp://creativecommons.org/licenses/by/4.0/
dc.rightsinfo:eu-repo/semantics/openAccess
dc.titleFarmacocinética poblacional en el manejo empírico de infecciones en pacientes con neoplasias hematológicas y neutropenia febril pos-quimioterapia
dc.typeTrabajo de grado - Maestría


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