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

New York University School of Medicine, New York City, NY, USA.
Expert Opinion on Drug Metabolism & Toxicology (Impact Factor: 2.83). 11/2010; 6(12):1551-64. DOI: 10.1517/17425255.2010.531259
Source: PubMed


Iloperidone is a newly commercialized second-generation (atypical) antipsychotic approved for the acute treatment of schizophrenia in adults.
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.
the reader will have an understanding of the pharmacokinetics and overall metabolism of iloperidone within the context of efficacy and safety.
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.

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    • "Its elimination half-life (t1/2) ranges from 18 hours for extensive cytochrome P450 2D6 (CYP2D6) metabolizers to 33 hours for poor metabolizers. The bioavailability of iloperidone is 96%.6 It is metabolized in the liver by the CYP3A4 and CYP2D6 enzyme pathways and circulates 95% bound to serum proteins.6 "
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    ABSTRACT: Schizophrenia is a devastating neuropsychiatric disease with a worldwide prevalence of approximately 0.5%-1%. Since many patients do not achieve adequate symptom relief from available agents, alternate pharmacotherapeutic approaches are needed. In this context, iloperidone was recently approved by the US Food and Drug Administration for the treatment of schizophrenia. This paper first reviews its pharmacodynamic and pharmacokinetic profiles, emphasizing their clinical relevance. Next, it summarizes the literature on its acute and maintenance efficacy, safety, and tolerability. It then considers pharmacogenetic data which may help to predict response and risk of cardiac arrhythmias with this agent. Finally, it critically positions iloperidone relative to other first- and second-generation antipsychotics.
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    ABSTRACT: In this article we investigate the post-launch retail prescription trends of asenapine (Saphris(®), Merck and Co.) and iloperidone (Fanapt(®), Vanda Pharmaceuticals Inc./Novartis), two new atypical antipsychotics to launch in the United States market in October 2009 and January 2010, respectively. In the first 12 months following the asenapine launch, and in the nine months since the iloperidone launch, asenapine and iloperidone have secured 0.22 and 0.10 percent of the total prescription market; however, both products nearly double those respective shares when total prescriptions are isolated to new patient prescriptions (0.44% for asenapine and 0.17% for iloperidone). Since launch, asenapine has shown stronger signs of growth, largely attributed to its approval in multiple indications as compared to iloperidone's single indication.
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