Pharmacokinetic-pharmacodynamic modeling of severity levels of extrapyramidal side effects with markov elements.

ABSTRACT: A major problem in the treatment of schizophrenic patients with current antipsychotic drugs, mainly acting as dopamine-2 receptor antagonists, is the occurrence of side effects such as extrapyramidal symptoms (EPS). Meta-analyses of summary data of EPS occurrence, and receptor occupancies inferred from mean plasma concentrations, have shown the incidence of EPS to rise when receptor occupancy is above ~80%. In this analysis, individual longitudinal EPS data from 2,630 patients participating in one of seven different trials and treated with haloperidol, paliperidone, ziprasidone, olanzapine, JNJ-37822681, or placebo were analyzed using a continuous time probability model with Markov elements. The developed pharmacokinetic-pharmacodynamic model describes the longitudinal changes of spontaneo

SUBMITTER: Pilla Reddy V 

PROVIDER: S-EPMC3603470 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature