Optimisation of in vitro experimental design for human cytochrome P450 mechanisms-based inhibition

Optimisation of in vitro experimental design for human cytochrome P450 mechanisms-based inhibition

Critical evaluation of the published literature showed that there are considerable variations in the experimental procedures and methods of data analysis used to characterise MBI. These variations may have contributed to reports of differing values of MBI kinetic parameters for a number of compounds...

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Main Author: Ghanbari, Fatemeh
Published: University of Sheffield 2008
Subjects:
615.70045
Online Access:http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.489050
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spelling ndltd-bl.uk-oai-ethos.bl.uk-4890502015-03-20T05:12:05ZOptimisation of in vitro experimental design for human cytochrome P450 mechanisms-based inhibitionGhanbari, Fatemeh2008Critical evaluation of the published literature showed that there are considerable variations in the experimental procedures and methods of data analysis used to characterise MBI. These variations may have contributed to reports of differing values of MBI kinetic parameters for a number of compounds. The influence of applying different values of MBI kinetic parameter on the predicted maximal fold reduction in in vivo intrinsic clearance is likely to be greatest for those compounds of intermediate inhibitory potency. However, such an effect also depends on the fraction of net clearance of substrate subject to MBI, and the pre-systemic exposure to the inhibitor.615.70045University of Sheffieldhttp://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.489050Electronic Thesis or Dissertation
collection NDLTD
sources NDLTD
topic 615.70045
spellingShingle 615.70045
Ghanbari, Fatemeh
Optimisation of in vitro experimental design for human cytochrome P450 mechanisms-based inhibition
description Critical evaluation of the published literature showed that there are considerable variations in the experimental procedures and methods of data analysis used to characterise MBI. These variations may have contributed to reports of differing values of MBI kinetic parameters for a number of compounds. The influence of applying different values of MBI kinetic parameter on the predicted maximal fold reduction in in vivo intrinsic clearance is likely to be greatest for those compounds of intermediate inhibitory potency. However, such an effect also depends on the fraction of net clearance of substrate subject to MBI, and the pre-systemic exposure to the inhibitor.
author Ghanbari, Fatemeh
author_facet Ghanbari, Fatemeh
author_sort Ghanbari, Fatemeh
title Optimisation of in vitro experimental design for human cytochrome P450 mechanisms-based inhibition
title_short Optimisation of in vitro experimental design for human cytochrome P450 mechanisms-based inhibition
title_full Optimisation of in vitro experimental design for human cytochrome P450 mechanisms-based inhibition
title_fullStr Optimisation of in vitro experimental design for human cytochrome P450 mechanisms-based inhibition
title_full_unstemmed Optimisation of in vitro experimental design for human cytochrome P450 mechanisms-based inhibition
title_sort optimisation of in vitro experimental design for human cytochrome p450 mechanisms-based inhibition
publisher University of Sheffield
publishDate 2008
url http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.489050
work_keys_str_mv AT ghanbarifatemeh optimisationofinvitroexperimentaldesignforhumancytochromep450mechanismsbasedinhibition
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