Pharmacokinetic–Pharmacodynamic Modeling of Severity levels of extrapyramidal Side effects with Markov elements

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.
[2012]

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