The usage of a three-compartment model to investigate the metabolic differences between hepatic reductase null and wild-type mice

Lydia Hill; Mark Andrew Joseph Chaplain; Roland Wolf; Yury Kapelyukh

doi:10.1093/imammb/dqv029

The usage of a three-compartment model to investigate the metabolic differences between hepatic reductase null and wild-type mice

Lydia Hill, Mark Andrew Joseph Chaplain, Roland Wolf, Yury Kapelyukh

Applied Mathematics

Research output: Contribution to journal › Article › peer-review

Abstract

The Cytochrome P450 (CYP) system is involved in 90% of the human body’s interactions with xenobiotics and due to this, it has become an area of avid research including the creation of transgenic mice. This paper proposes a three-compartment model which is used to explain the drug metabolism in the Hepatic Reductase Null (HRN) mouse developed by the University of Dundee (Henderson, C. J., Otto, D. M. E., Carrie, D., Magnuson, M. A., McLaren, A. W., Rosewell, I. and Wolf, C. R. (2003) Inactivation of the hepatic cytochrome p450 system by conditional deletion of hepatic cytochrome p450 reductase. J. Biol. Chem. 278, 13480–13486). The model is compared with a two-compartment model using experimental data from studies using wild-type and HRN mice. This comparison allowed for metabolic differences between the two types of mice to be isolated. The three sets of drug data (Gefitinib, Midazolam and Thalidomide) showed that the transgenic mouse has a decreased rate of metabolism.

Original language	English
Number of pages	13
Journal	Mathematical Medicine and Biology
Volume	Advance Access
DOIs	https://doi.org/10.1093/imammb/dqv029
Publication status	Published - 5 Oct 2015

Keywords

cytochrome P450 enzymes
compartment models
hepatic reductase null mice
drug metabolism

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© 2015, the Author(s). Published by Oxford University Press on behalf of the Institute of Mathematics and its Applications. All rights reserved. This work is made available online in accordance with the publisher’s policies. This is the author created, accepted version manuscript following peer review and may differ slightly from the final published version. The final published version of this work is available at http://imammb.oxfordjournals.org/content/early/2015/10/04/imammb.dqv029.full
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title = "The usage of a three-compartment model to investigate the metabolic differences between hepatic reductase null and wild-type mice",

abstract = "The Cytochrome P450 (CYP) system is involved in 90% of the human body{\textquoteright}s interactions with xenobiotics and due to this, it has become an area of avid research including the creation of transgenic mice. This paper proposes a three-compartment model which is used to explain the drug metabolism in the Hepatic Reductase Null (HRN) mouse developed by the University of Dundee (Henderson, C. J., Otto, D. M. E., Carrie, D., Magnuson, M. A., McLaren, A. W., Rosewell, I. and Wolf, C. R. (2003) Inactivation of the hepatic cytochrome p450 system by conditional deletion of hepatic cytochrome p450 reductase. J. Biol. Chem. 278, 13480–13486). The model is compared with a two-compartment model using experimental data from studies using wild-type and HRN mice. This comparison allowed for metabolic differences between the two types of mice to be isolated. The three sets of drug data (Gefitinib, Midazolam and Thalidomide) showed that the transgenic mouse has a decreased rate of metabolism.",

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author = "Lydia Hill and Chaplain, {Mark Andrew Joseph} and Roland Wolf and Yury Kapelyukh",

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AU - Chaplain, Mark Andrew Joseph

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AU - Kapelyukh, Yury

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N2 - The Cytochrome P450 (CYP) system is involved in 90% of the human body’s interactions with xenobiotics and due to this, it has become an area of avid research including the creation of transgenic mice. This paper proposes a three-compartment model which is used to explain the drug metabolism in the Hepatic Reductase Null (HRN) mouse developed by the University of Dundee (Henderson, C. J., Otto, D. M. E., Carrie, D., Magnuson, M. A., McLaren, A. W., Rosewell, I. and Wolf, C. R. (2003) Inactivation of the hepatic cytochrome p450 system by conditional deletion of hepatic cytochrome p450 reductase. J. Biol. Chem. 278, 13480–13486). The model is compared with a two-compartment model using experimental data from studies using wild-type and HRN mice. This comparison allowed for metabolic differences between the two types of mice to be isolated. The three sets of drug data (Gefitinib, Midazolam and Thalidomide) showed that the transgenic mouse has a decreased rate of metabolism.

AB - The Cytochrome P450 (CYP) system is involved in 90% of the human body’s interactions with xenobiotics and due to this, it has become an area of avid research including the creation of transgenic mice. This paper proposes a three-compartment model which is used to explain the drug metabolism in the Hepatic Reductase Null (HRN) mouse developed by the University of Dundee (Henderson, C. J., Otto, D. M. E., Carrie, D., Magnuson, M. A., McLaren, A. W., Rosewell, I. and Wolf, C. R. (2003) Inactivation of the hepatic cytochrome p450 system by conditional deletion of hepatic cytochrome p450 reductase. J. Biol. Chem. 278, 13480–13486). The model is compared with a two-compartment model using experimental data from studies using wild-type and HRN mice. This comparison allowed for metabolic differences between the two types of mice to be isolated. The three sets of drug data (Gefitinib, Midazolam and Thalidomide) showed that the transgenic mouse has a decreased rate of metabolism.

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DO - 10.1093/imammb/dqv029

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VL - Advance Access

JO - Mathematical Medicine and Biology

JF - Mathematical Medicine and Biology

ER -

The usage of a three-compartment model to investigate the metabolic differences between hepatic reductase null and wild-type mice

Abstract

Keywords

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