Iloperidone: chemistry, pharmacodynamics, pharmacokinetics and metabolism, clinical efficacy, safety and tolerability, regulatory affairs, and an opinion.

IMPORTANCE OF THE FIELD: Iloperidone is a newly commercialized second-generation (atypical) antipsychotic approved for the acute treatment of schizophrenia in adults. AREAS COVERED IN THIS REVIEW: the purpose of this review is to describe the pharmacokinetic profile of iloperidone and its clinical implications in the treatment of schizophrenia. Background information is also provided regarding chemistry, pharmacodynamics, clinical efficacy and safety data, and regulatory affairs. WHAT THE READER WILL GAIN: the reader will have an understanding of the pharmacokinetics and overall metabolism of iloperidone within the context of efficacy and safety. TAKE HOME MESSAGE: time to peak plasma concentration occurs in 2 - 4 h but elimination half-life is 18 h for extensive CYP2D6 metabolizers and 33 h for poor CYP2D6 metabolizers, suggesting that once or twice daily dosing would be feasible. Dizziness and/or postural hypotension are the limiting factors for how fast iloperidone can be titrated, and is explained by iloperidone and its metabolites' norepinephrine alpha 1 antagonism. Efficacy of iloperidone appears similar to that for ziprasidone and haloperidol, but iloperidone may be inferior in efficacy to risperidone. Iloperidone can prolong the ECG QT interval. The tolerability profile of iloperidone is noteworthy in terms of modest weight gain, no medically important changes in lipid and glucose, little in the way of prolactin elevation, and an absence of extrapyramidal adverse effects, including akathisia.