ABSTRACT
Population pharmacokinetic (popPK) models constitute a valuable tool for characterizing the pharmacokinetic properties of once-monthly long-acting injectable aripiprazole (LAI aripiprazole) and quantifying the sources of variability in drug exposure. Our aim is to develop a popPK model of both aripiprazole and its metabolite dehydro-aripiprazole in patients treated with LAI aripiprazole, and to personalize the dosing regimen of aripiprazole across different sub-groups of patients. This is a prospective study investigating the pharmacokinetics of LAI aripiprazole. A total of 93 patients were included, 21 for model development and 71 for external model evaluation. A one-compartment model with linear absorption and elimination adequately described both aripiprazole and dehydro-aripiprazole concentrations. The weight of the patients has been shown to be the factor that most influences the absorption. However, the metabolizing phenotype for CYP2D6 and the concomitant treatment with strong inhibitors of this cytochrome have been shown to be the covariates that most influence total drug exposure. This is the first popPK model developed for LAI aripiprazole that includes aripiprazole and its main active metabolite, dehydroaripiprazole. It provides a personalized dosage recommendation that maximizes the probability of achieving optimal therapeutic concentrations and minimizes the difficulties associated with trial-and-error therapeutic strategies carried out in clinical practice.
Subject(s)
Antipsychotic Agents , Humans , Aripiprazole/pharmacology , Aripiprazole/therapeutic use , Antipsychotic Agents/therapeutic use , Precision Medicine , Prospective Studies , Cytochrome P-450 CYP2D6/geneticsABSTRACT
El síndrome de fatiga crónica (SFC) es una de las principales causas de absentismo escolar. Presentamos el caso de un varón de 14 años con síndrome de fatiga crónica después de una mononucleosis infecciosa; que le ocasiona gran incapacidad y preocupación sobre la enfermedad. Se discute el mal pronóstico de este paciente e hipotetizamos su posible asociación con la cronicidad de la enfermedad, la psicopatología de la familia y del paciente y el hecho de mantener la creencia de que la enfermedad se debe a una causa orgánica (AU)
Chronic fatigue syndrome (CFS) is a major cause of school absenteeism. A 14-year old boy with CFS following an infectious mononucleosis with great disability and signiicant concerns regarding the origin of the illness is presented. Factors associated with the poor prognosis such as the illness chronicity, the family psychopathology and the longstanding belief by the patient that illness has an organic origin are discussed (AU)
