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

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

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 languageEnglish
Number of pages13
JournalMathematical Medicine and Biology
VolumeAdvance Access
DOIs
Publication statusPublished - 5 Oct 2015

Keywords

  • cytochrome P450 enzymes
  • compartment models
  • hepatic reductase null mice
  • drug metabolism

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