RESUMO
The aim of the present study was to determinate the factors affecting carbamazepine (CBZ) clearance (CL) in adults with epilepsy using a mixed-effect model and sparse data collected during routine clinical care. The patient population comprised 104 adults receiving CBZ. A total of 161 CBZ steady state serum concentration samples were analyzed. Population CL was calculated by using NONMEM with a one compartment model with first-order absorption and elimination. The following covariates were tested for their influence on clearance (CL): total body weight, age, dose/day, sex, surface area (SA) and comedication with primidone (PRIM), ualproic acid or phenytoin (DFH). The final regression model for carbamazepine clearance found best to describe the data was: CL = (0.614 SA + 0.0016 dose/day)(1 + 0.278 DFH)(1 + 0.326 PRIM).
Assuntos
Carbamazepina/farmacocinética , Epilepsia/metabolismo , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
The aim of the present study was to determinate the factors affecting carbamazepine (CBZ) clearance (CL) in adults with epilepsy using a mixed-effect model and sparse data collected during routine clinical care. The patient population comprised 104 adults receiving CBZ. A total of 161 CBZ steady state serum concentration samples were analyzed. Population CL was calculated by using NONMEM with a one compartment model with first-order absorption and elimination. The following covariates were tested for their influence on clearance (CL): total body weight, age, dose/day, sex, surface area (SA) and comedication with primidone (PRIM), valproic acid or phenytoin (DFH). The final regression model for carbamazepine clearance found best to describe the data was: CL = (0.614 SA + 0.0016 dose/day)(1 + 0.278 DFH)(1 + 0.326 PRIM).
El objetivo de este trabajo es determinar los factores que influyen en el aclaramiento (CL) de carbamacepina (CBZ) en pacientes epilépticos adultos usando un modelo de efectos mixtos y datos de concentraciones séricas de CBZ generados del cuidado rutinario de los pacientes. El número de pacientes incluidos en el estudio fue de 104. Se analizaron un total de 161 concentraciones séricas de CBZ en el estado estacionario. El aclaramiento poblacional se determinó con el programa NONMEM aplicando un modelo monocompartimental con absorción y eliminación de primer orden. Se analizó la influencia de las siguientes covariables sobre el CL: peso corporal total, edad, dosis/día, sexo, superficie corporal (SC) y la comedicación con primidona (PRIM), ácido valproico o difenilhidantoína (DFH). El modelo final de regresión obtenido es el siguiente: CL = (0.614 SC + 0.0016 dosis/día)( 1+ 0.278 DFH)(1 + 0.326 PRIM).