Long-term efficacy and safety of iloperidone: an update

Rado, Jeffrey; Janicak, Philip G.

doi:10.2147/ndt.s37824

Cited by 5 publications

(5 citation statements)

References 24 publications

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“…Although some differences were observed between the significances of M 1 and M 2 at different time points (particularly in the C 28-4 /D and C 28-12 /D ratio), which may have been due to the limited sample size, patients with the CYP2D6*10 T/T genotype were generally observed to exhibit a higher steady-state plasma concentration of M 1 and a lower steady-state plasma concentration of M 2 relative to the other genotype groups at all of the time points. Therefore, the CYP2D6*10 genotypes affected the steady-state concentrations of iloperidone and its metabolites, which is consistent with the fact that M 2 is primarily formed by CYP2D6 [19,20] .…”

Section: Discussionsupporting

confidence: 81%

Influences of CYP2D6*10 polymorphisms on the pharmacokinetics of iloperidone and its metabolites in Chinese patients with schizophrenia: a population pharmacokinetic analysis

Pei

Huang

et al. 2016

Acta Pharmacol Sin

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Aim: Iloperidone is an atypical antipsychotic drug that is mainly metabolized by CYP2D6, CYP3A4, and cytosolic enzymes. Previous studies show that extensive and poor metabolizers of CYP2D6 exhibit different plasma concentrations of iloperidone and its metabolites. The aim of this study was to develop a parent-metabolite population pharmacokinetic (PPK) model to quantify the effects of CYP2D6*10 allele on the pharmacokinetics of iloperidone and its metabolites in Chinese schizophrenia patients. Methods: Seventy Chinese schizophrenia patients were enrolled, from whom limited blood samples were collected on d 15 (0 h) and d 28 (0, 4 and 12 h after drug administration). The plasma concentrations of iloperidone and its metabolites M 1 (P-88) and M 2 (P-95) were simultaneously detected using a validated HPLC-MS assay. CYP2D6*10 (rs1065852) genotyping was performed. A PPK model was developed based on data from the patients using the NONMEM software (version 7.2). A one-compartment model with first-order absorption and elimination was used to describe the pharmacokinetic data related to iloperidone and its metabolites. Results: Patients with the CYP2D6*10 T/T genotype had significantly higher concentrations of iloperidone and M 1 , and lower concentrations of M 2 than the patients with C/C or C/T genotypes. The CYP2D6*10 genotype affected the elimination constants for transformation of iloperidone to the metabolites M 1 (K 23 ) and M 2 (K 24 ). The K 23 value of the patients with T/T genotype was 1.34-fold as great as that of the patients with C/C or C/T genotype. The K 24 value of the patients with C/T and T/T genotypes was 0.693-and 0.492-fold, respectively, as low as that of the patients with C/C genotype. Conclusion: CYP2D6*10 mutations affect the pharmacokinetics of iloperidone and its metabolites in Chinese schizophrenia patients, suggesting that the clinical doses of iloperidone for patients with CYP2D6*10 mutations need to be optimized.

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Section: Discussionsupporting

confidence: 81%

Influences of CYP2D6*10 polymorphisms on the pharmacokinetics of iloperidone and its metabolites in Chinese patients with schizophrenia: a population pharmacokinetic analysis

Pei

Huang

et al. 2016

Acta Pharmacol Sin

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“…Iloperidone (ILP) was recently approved by the US Food and Drug Administration for the acute treatment of schizophrenia (Arif and Mitchell, 2011[4]; Rado and Janicak, 2014[125]).…”

Section: Introductionmentioning

confidence: 99%

“…Moreover ILP shows low affinity for norepinephrine α 2A , α 2B , ß 1 , ß 2 , receptors, histamine H 1 receptors, dopamine D 1 and D 5 receptors. Negligible affinity is for muscarinic µ1–µ5 receptors, dopamine and norepinephrine re-uptake transporters (Rado and Janicak, 2014[125]).…”

Section: Introductionmentioning

confidence: 99%

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Clinical Pharmacokinetics of Atypical Antipsychotics: An Update

et al. 2018

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Therapeutic drug monitoring studies have generally concentrated on controlling compliance and avoiding side effects by maintaining long-term exposure to minimally effective blood concentrations. The rationale for using therapeutic drug monitoring in relation to second-generation antipsychotics is still being discussed at least with regard to the real clinical utility, but there is evidence that it can improve efficacy, especially when patients do not respond or develop side effects using therapeutic doses. Furthermore, drug plasma concentration determinations can be of some utility in medico-legal problems. This review concentrates on the clinical pharmacokinetic data related to clozapine, risperidone, paliperidone, olanzapine, quetiapine, amisulpride, ziprasidone, aripiprazole, sertindole, asenapine, iloperidone, lurasidone, brexpiprazole and cariprazine and briefly considers the main aspects of their pharmacodynamics. Optimal plasma concentration ranges are proposed for clozapine, risperidone, paliperidone and olanzapine because the studies of quetiapine, amisulpride, asenapine, iloperidone and lurasidone provide only limited information and there is no direct evidence concerning ziprasidone, aripiprazole, sertindole, brexpiprazole and cariprazine: the few reported investigations need to be confirmed and extended.

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“…Schizophrenia occurs worldwide and is among the most severe devastating mental disorders [Rado and Janicak, 2014]. This severe mental disorder affects 1% of the world population and is characterized by psychotic symptoms such as hallucinations, delusions or disorganized thinking and cognitive, affective and psychosocial impairment [Schultz and Andreasen, 1999].…”

Section: Introductionmentioning

confidence: 99%