Abstract
Over the last two decades, pharmacogenetics and pharmacokinetics have been increasingly used in clinical practice in Psychiatry due to the high variability regarding response and side effects of antipsychotic drugs. Specifically, long-acting injectable (LAI) antipsychotics have different pharmacokinetic profile than oral formulations due to their sustained release characteristics. In addition, most of these drugs are metabolized by CYP2D6, whose interindividual genetic variability results in different metabolizer status and, consequently, into different plasma concentrations of the drugs. In this context, there is consistent evidence which supports the use of therapeutic drug monitoring (TDM) along with pharmacogenetic tests to improve safety and efficacy of antipsychotic pharmacotherapy. This comprehensive review aims to compile all the available pharmacokinetic and pharmacogenetic data regarding the three major LAI atypical antipsychotics: risperidone, paliperidone and aripiprazole. On the one hand, CYP2D6 metabolizer status influences the pharmacokinetics of LAI aripiprazole, but this relation remains a matter of debate for LAI risperidone and LAI paliperidone. On the other hand, developed population pharmacokinetic (popPK) models showed the influence of body weight or administration site on the pharmacokinetics of these LAI antipsychotics. The combination of pharmacogenetics and pharmacokinetics (including popPK models) leads to a personalized antipsychotic therapy. In this sense, the optimization of these treatments improves the benefit–risk balance and, consequently, patients’ quality of life.
Highlights
Schizophrenia is a severe mental disorder that is presented clinically heterogeneously in patients
Limited evidence has restricted the proper characterization of their pharmacokinetic properties, regarding long-acting injectable (LAI) of risperidone, paliperidone and aripiprazole
The role of CYP2D6 has been demonstrated on the PK of LAI. Aripriprazole, it remains uncertain for LAI risperidone and LAI paliperidone
Summary
Schizophrenia is a severe mental disorder that is presented clinically heterogeneously in patients. The pharmacological treatment of schizophrenia is based on antipsychotics, a family of drugs which are classified into two separate groups: first generation or typical (i.e., haloperidol, chlorpromazine) and second generation or atypical (i.e., risperidone, paliperidone, aripiprazole) Both of them present affinity toward D2 receptors and reduce positive symptoms. Compared to classical pharmacokinetics, where several samples at different time points are collected from a patient to estimate their individual pharmacokinetic parameters (clearance, distribution volume, half-life, etc.), population pharmacokinetics (popPK) analyzes the pooled data available of several patients in order to estimate pharmacokinetic parameter values and their variance, identify covariates and study the random effects (parameter variance which cannot be explained by covariates) All this information implemented in a mathematical model (popPK models) plus Bayesian computational methods allows us to estimate our patients’ individual pK parameters, which can be a very helpful tool to individualize dosing and optimize the treatment efficacy and safety. LAI-antipsychotics pharmacogenetics and pharmacokinetics, including the existing popPK models as a crucial tool for predicting drug exposure, focusing on risperidone, paliperidone and aripiprazole
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
