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'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. , 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.
authors.forename: Lydia
authors.initials: L
authors.lastname: Hill
authors.forename: Mark A J
authors.initials: MAJ
authors.lastname: Chaplain
authors.forename: Roland
authors.initials: R
authors.lastname: Wolf
authors.forename: Yury
authors.initials: Y
authors.lastname: Kapelyukh
mesh_terms: D020533:Angiogenesis Inhibitors / Q000378:metabolism; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004195:Disease Models, Animal; D018757:GABA Modulators / Q000378:metabolism; D000077156:Gefitinib; D008099:Liver / Q000201:enzymology*; D051379:Mice; D008822:Mice, Transgenic / Q000378:metabolism; D008874:Midazolam / Q000378:metabolism; D008954:Models, Biological; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000378:metabolism; D011799:Quinazolines / Q000378:metabolism; D013792:Thalidomide / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D018757:GABA Modulators; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D013792:Thalidomide; D003577:Cytochrome P-450 Enzyme System; D009251:NADPH-Ferrihemoprotein Reductase; D008874:Midazolam; D000077156:Gefitinib
keywords: compartment models; cytochrome P450 enzymes; drug metabolism; hepatic reductase null mice