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    Identification of specific intrinsic liver clearance from a precision-cut liver-slice experiment

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    Authors
    Eijkeren JCH van
    Series/Report no.
    RIVM Rapport 630020002
    Type
    Report
    Language
    en
    
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    Title
    Identification of specific intrinsic liver clearance from a precision-cut liver-slice experiment
    Translated Title
    Identificatie van de specifieke intrinsieke leverklaring uit een liver-slice experiment
    Publiekssamenvatting
    A model describing metabolism experiments with precision-cut liver-slices incubated in a culture medium is developed. Formal mathematical techniques are presented that solve the problem of identifying the specific intrinsic liver clearance from the experimental data. The formal solution is discussed from the perspective of experimental practice. A necessary condition for identification is sampling parent compound in slice or culture medium. However, sampling parent compound in slice and additionally metabolite pooled from medium and slice is required by experimental limitations. Moreover it appears that identification is unreliable when the value of the slice's intrinsic clearance exceeds the diffusion rate of transport of the parent compound from the culture medium to the slice, a condition to be verified only afterwards.
    Er wordt een model ontwikkeld dat metabolisme experimenten met liver-slices beschrijft die geincubeerd worden in een kweekmedium. Er worden formele wiskundige technieken geintroduceerd die het probleem van de identificatie van de specifieke intrinsieke leverklaring oplossen. Deze formele oplossing wordt bediscussieerd vanuit het oogpunt van de experimentele praktijk. Een nodige voorwaarde voor identificatie is de bemonstering van de moederstof in de slice of het kweekmedium. Maar door de experimentele limitaties is het vereist de moederstof in de slice te bemonsteren en daarnaast ook de metabolieten samengevoegd uit slice en kweekmedium. Bovendien blijkt dat de gevonden waarde voor de klaring onbetrouwbaar is als deze groter is dan de diffusiesnelheid van transport van moederstof van kweekmedium naar slice.
    Publisher
    Rijksinstituut voor Volksgezondheid en Milieu RIVM
    URI
    http://hdl.handle.net/10029/9612
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