Clinical pharmacokinetics of atypical antipsychotics: a critical review of the relationship between plasma concentrations and clinical response.

摘要: In the past, information about dose-clinical effectiveness of typical antipsychotics was not complete and this led to risk extrapyramidal adverse effects. This, together with intention improving patients' quality life therapeutic compliance, resulted in development atypical or second-generation (SGAs). This review will concentrate on pharmacokinetics metabolism clozapine, risperidone, olanzapine, quetiapine, amisulpride, ziprasidone, aripiprazole sertindole, discuss main aspects their pharmacodynamics. psychopharmacology, drug monitoring studies have generally concentrated controlling compliance avoiding effects by keeping long-term exposure minimal effective blood concentration. The rationale for using relation SGAs is still a matter debate, but there growing evidence that it can improve efficacy, especially when patients do respond doses they develop Here, we literature concerning relationships between plasma concentrations clinical responses dividing basis length observation periods. Studies clozapine evidenced positive relationship response, threshold 350-420 ng/mL associated good response. usefulness well established because high increase epileptic seizures. Plasma seem be influenced many factors such as altered cytochrome P450 1A4 activity, age, sex smoking. pharmacological risperidone depend sum its 9-hydroxyrisperidone metabolite, so parent compound alone lead erroneous interpretations. Despite large variability concentrations, lack fixed dosages, discrepancies results, seems active moiety may useful. However, no concentration range has yet been clearly established. A parkinsonian side found 74 ng/mL. Moreover, particularly useful switch oral long-acting injectable form. reviewed olanzapine strongly indicate outcomes concentrations. Olanzapine considered very assessing efficacy events. 20-50 found. There little favour existence quetiapine responses, an optimal identified. Positron emission tomography receptor blockade indicated discrepancy time course occupancy value practice controversial. Preliminary data suggested amisulpride 367 improvement. 100-400 proposed from non-systematic experience. direct ranges sertindole.