Identification of specific intrinsic liver clearance from a precision-cut liver-slice experiment
Eijkeren JCH van
Eijkeren JCH van
Citations
Altmetric:
Series / Report no.
Open Access
Type
Report
Language
en
Date of publication
2000-06-20
Year of publication
Research Projects
Organizational Units
Journal Issue
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
Published in
Abstract
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.
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.
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.
Description
Publisher
Sponsors
RIVM