Developing In Vitro–In Vivo Correlation of Risperidone Immediate Release Tablet

Saibi, Yardi; Sato, Hitoshi; Tachiki, Hidehisa

doi:10.1208/s12249-012-9814-3

Cited by 32 publications

(19 citation statements)

References 12 publications

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“…As the second-generation antipsychotics, risperidone, is one of the most frequently prescribed antipsychotics, and it has potent antagonistic properties for serotonin-5HT 2 and dopamine D 2 receptors [10,11] . In vivo, risperidone is extensively metabolized to 9-hydroxyrisperidone mainly by human CYP450 CYP2D6 and partly by CYP3A4 [12] .…”

Section: Effects Of 24 Cyp2d6 Variants Found In the Chinese Populatiomentioning

confidence: 99%

Effects of 24 CYP2D6 Variants Found in the Chinese Population on the Metabolism of Risperidone

Wang

Zhan

et al. 2015

Pharmacology

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Aims: Cytochrome P450 (CYP450) 2D6 is an important member of the P450 enzyme superfamily and responsible for clearing 25% of clinically important drugs. The aim of this study was to assess the catalytic characteristics of 24 CYP2D6 allelic isoforms found in the Chinese population and their effects on the metabolism of risperidone in vitro. Methods: Insect microsomes expressing wild-type CYP2D6 and 24 CYP2D6 allelic variants were incubated with 20-1,000 μmol/l risperidone for 40 min at 37°C. After termination, risperidone and 9-OH risperidone, the metabolite of risperidone, were precipitated and used for signal collection by ultra-performance liquid-chromatography tandem mass spectrometry. Results: Among 24 CYP2D6 variants tested, 2 variants (CYP2D6*92 and CYP2D6*96) were found to be with no detectable activity. Two variants (E215K and R440C) exhibited higher intrinsic clearance values than the wild-type protein, while the remaining 20 CYP2D6 allelic variants exhibited significantly decreased clearance values (2.01-87.56%) compared to CYP2D6*1. Conclusion: These findings suggest that more attention should be directed to subjects carrying these infrequent CYP2D6 alleles when administering risperidone in the clinic. This is the first report of all these novel alleles for risperidone metabolism, providing fundamental data for further clinical studies on CYP2D6 alleles.

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Section: Effects Of 24 Cyp2d6 Variants Found In the Chinese Populatiomentioning

confidence: 99%

Effects of 24 CYP2D6 Variants Found in the Chinese Population on the Metabolism of Risperidone

Wang

Zhan

et al. 2015

Pharmacology

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“…As Dunne et al 97 published, the relationship between the in vivo and in vitro dissolution may be expressed in terms of a relationship between the related functions such as the odds functions [Equation (13)], the hazard functions [Equation (14)] or the reversed hazard functions [Equation (15)]. …”

Section: Two-stage Methodsmentioning

confidence: 99%

“…As a model-independent approach, deconvolution have gained popularity in the last years because it refuses the assumption of model-dependency, allowing more flexibility 2,3,9,10,11,[14][15][16][17]38,55,56,96,97,103,104,[119][120][121][122][123][124][125][126][127][128] (see Table 7). However, the use of averaged data in some articles is still controversial and it has become itself an important research field.…”

Section: Advantages and Limitations Of Ivivc Modeling Approachesmentioning

confidence: 99%

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In vitro–in vivocorrelations: general concepts, methodologies and regulatory applications

González‐García

Mangas‐Sanjuán

Merino-Sanjuán

et al. 2015

Drug Development and Industrial Pharmacy

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The major objective of in vitro-in vivo correlations is to be able to use in vitro data to predict in vivo performance serving as a surrogate for an in vivo bioavailability test and to support biowaivers. Therefore, the aims of this review are: (i) to clarify the factors involved during bio-predictive dissolution method development; and (ii) the elements that may affect the mathematical analysis in order to exploit all information available. This article covers the basic aspects of dissolution media and apparatus used in the development of in vivo predictive dissolution methods, including the latest proposals in this field as well as the summary of the mathematical methods for establishing the in vitro-in vivo relationship and their scope and limitations. The incorporation of physiological relevant factors in the in vitro dissolution method is essential to get accurate in vivo predictions. Standard quality control dissolution methods do not necessarily reflect the in vivo behavior, so they rarely are useful for predicting in vivo performance. The combination of physiological based dissolution methods with physiological-based pharmacokinetics models incorporating gastrointestinal variables will lead to robust tools for drug and formulation development, nevertheless their regulatory use for biowaiver application still require harmonization of the mathematical methods proposed and more detailed recommendations about the procedures for setting up dissolution specifications.

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“…Recently, with the development of mechanistic oral absorption models, scientists have started to explore deconvolution of the plasma concentration vs. time profiles against mechanistic absorption models to obtain in vivo dissolution (Saibi et al 2012;Turner 2012;Zhang et al 2011;Grbic et al 2011;Lionberger et al 2012). Deconvolution against physiologically based absorption models considers factors such as pH in the GI tract, GI transit, permeability, first pass, etc.…”

Section: Mathematical Approachesmentioning

confidence: 99%