Dosificación individualizada de ciclosporina en niños transplantados renal.
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Fecha
2008
Autores
Profesor/a Guía
Idioma
es
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Universidad Andrés Bello
Nombre de Curso
Licencia CC
Licencia CC
Resumen
RESUMEN:
En transplante renal, la ciclosporina es el fármaco más empleado corno agente
inrnunosupresor.
La gran variabilidad interindividual e intraindividual de su farrnacocinética y su estrecho
margen terapéutico, indican la necesidad de monitorear las concentraciones sanguíneas
(TDM) y de individualizar las dosis de ciclosporina que aseguren la sobrevida del
transplante, evitando la toxicidad por sobredosificación, o el rechazo por sub-dosificación.
El conocimiento del clearance oral individual de ciclosporina (CLIP) y de la AUC(O-12hrs),
permite el cálculo de dosis individualizada de Neoral®.
En el año 2005, el equipo del Dr Ke-Hua Wu, estudió la farrnacocinética poblacional de la
ciclosporina en un modelo monocompartimental con absorción y eliminación de orden 1 y
empleando el programa computacional NüNMEM, encontró una fórmula para el cálculo
del CLIP individual de la ciclosporina, que contempla la inclusión de las seis co-variables
más significativas que influyen en su farrnacocinética.
La muestra de sangre (C2), constituye en la actualidad, el mejor parámetro para monitorear
la dosificación de ciclosporina en Neoral®.
En un grupq de 16 adultos transplantados renal estables tratados con azatioprina,
prednisona y Neoral® se encontró la fórmula de regresión lineal que relaciona el AUC(O-12 hr)
y C2 y se pudo demostrar la estrecha relación que existe entre ellas (r = 0,92).
A través de un estudio retrospectivo realizado en dos grupos de niños transplantados renal
del Hospital Luis Calvo Mackenna se calcularon las dosis de Neoral® empleando el valor
del CLIP individual y la AUC(O-12 hrs), correspondientes a las C2 medidas en el laboratorio.
Estas dosis calculadas fueron comparadas con las dosis inicialmente administradas al
paciente de acuerdo al peso del enfermo.
En el grupo control de 13 niños, en que las muestras de C2 se tornaron respetando
rigurosamente los tiempos de torna de muestra, se encontró una correlación de 0,92 entre
dosis calculada y dosis administrada. En cambio en el grupo "Realidad Hospitalaria" de 17
pacientes en que se analizaron 229 muestras de C2 recolectadas durante los controles
médicos rutinarios, la correlación en.contrada fue más pobre con promedio de 0,50.
Con correctas muestras de C2, el modelo propuesto de cálculo de dosis de Neoral® tiene
una predicción de dosis del 85%.
ABSTRACT: Cyclosporine drug is the backbone of irnmunosuppressive treatments in kidney transplant. Its large inter- and intra-variability pharmacokinetic and the narrow therapeutic window, render the therapeutic drug monitoring (TDM) and the need of individualized doses of cyclosporine to ensure thesurvival oftransplantation, avoiding toxicity by overdose and the graft loss by a low-dosing. Knowledge of the individual cyclosporine oral clearance (CL/F) and AUC(O-12 hrs), allows the calculation of individualized Neoral® doses. In 2005, Dr Wu Ke-Hua and col. investigating population pharmacokinetics of cyclosporine, using a one-compartment model with first-order absorption and elimination, and using the (NONMEM) program, found a formula for calculating individual CL/F that includes the influence of six significant co-variables that affect their pharmacokinetics. The C2 sample is considered now the best parameter to monitor the CsA dosage in Neoral®. In a group of 16 adults stable kidney transplanted, treated with prednisone, azathioprine and Neoral®' was possible to find a linear relatioship between AUC(O-12 hrs) and C2, and demonstrate the close relationship between them(r=0,92). Through a retrospective study conducted on two groups of pediatric kidney transplant patients at Luis Calvo Mackenna Hospital, were calculated the Neoral® doses using the calculated individual CL/F value and the AUC(O-12 hrs), according the C2 measured in the laboratory. The calculated Neoral® doses were compared with doses administered to these patients, according the body weight. In the control group of 13 pediatric kidney transplants, in which samples were collected in accurate C2 time sampling, we found a good correlation 0,92, between predicted doses and administered dose. Not so in the group of 17 kidney transplanted patients denominated "Hospital Reality". In this group 229 C2 samples were recolected during routine medical controls and the analysis indicated a poor relationship between them. The proposed model to calculate Neoral doses, employing accurate C2 samples predicts 85% of calculated doses.
ABSTRACT: Cyclosporine drug is the backbone of irnmunosuppressive treatments in kidney transplant. Its large inter- and intra-variability pharmacokinetic and the narrow therapeutic window, render the therapeutic drug monitoring (TDM) and the need of individualized doses of cyclosporine to ensure thesurvival oftransplantation, avoiding toxicity by overdose and the graft loss by a low-dosing. Knowledge of the individual cyclosporine oral clearance (CL/F) and AUC(O-12 hrs), allows the calculation of individualized Neoral® doses. In 2005, Dr Wu Ke-Hua and col. investigating population pharmacokinetics of cyclosporine, using a one-compartment model with first-order absorption and elimination, and using the (NONMEM) program, found a formula for calculating individual CL/F that includes the influence of six significant co-variables that affect their pharmacokinetics. The C2 sample is considered now the best parameter to monitor the CsA dosage in Neoral®. In a group of 16 adults stable kidney transplanted, treated with prednisone, azathioprine and Neoral®' was possible to find a linear relatioship between AUC(O-12 hrs) and C2, and demonstrate the close relationship between them(r=0,92). Through a retrospective study conducted on two groups of pediatric kidney transplant patients at Luis Calvo Mackenna Hospital, were calculated the Neoral® doses using the calculated individual CL/F value and the AUC(O-12 hrs), according the C2 measured in the laboratory. The calculated Neoral® doses were compared with doses administered to these patients, according the body weight. In the control group of 13 pediatric kidney transplants, in which samples were collected in accurate C2 time sampling, we found a good correlation 0,92, between predicted doses and administered dose. Not so in the group of 17 kidney transplanted patients denominated "Hospital Reality". In this group 229 C2 samples were recolected during routine medical controls and the analysis indicated a poor relationship between them. The proposed model to calculate Neoral doses, employing accurate C2 samples predicts 85% of calculated doses.
Notas
Tesis (Químico Farmacéutico)
Palabras clave
Medicamentos -- Administración y Dosificación.