geoscience.net logo
+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

P450 humanized mice for the study of xenobiotics CYP3A4 as a paradigm


, : P450 humanized mice for the study of xenobiotics CYP3A4 as a paradigm. FASEB Journal 18(4-5): Abst 793 2

Animal models are widely used to examine metabolism, pharmacology and toxicology of xenobiotics including therapeutic agents. However, there are marked notable species differences in the expression and enzymatic functions of P450s between mice and rats, and humans. This is especially notable between mice and rats, commonly used experimental models, and humans. Human P450-expressing transgenic mice were generated using genomic clones, and mouse lines expressing the CYP2D6 and CYP3A4 genes were characterized and found to accurately express the corresponding enzymes higher than those found in human tissues. Highly sensitive LC-MS/MS was developed to perform drug metabolism and pharmacokinetic analyses using probe drugs. These novel P450 humanized mouse lines overcome the gap of species differences and offer a better system to study drug metabolism and disposition, and drug-drug interactions for the prediction of drug/chemical effects in humans. Moreover, these mice can serve as whole intact animal models for exploring endogenous substrates for human P450s, examining their biotransformations, and elucidating physiological consequences of human P450 expression in an integrated whole animal system. A CYP3A4 humanized mouse was produced that expressed high levels of enzymatically active protein in the gut. These mice exhibited altered pharmacokinetics to orally administered CYP3A4 substrates. They might be useful for the preclinical evaluation of orally administered drugs that are CYP3A4 substrates and to determine the effects of inhibitors of CYP3A4 on pharmacokinetics.

US$29.90


Other references

Böcher, W.O.; Schuchmann, M.; Link, R.; Hillenbrand, H.; Rahman, F.; Sprinzl, M.; Mudter, J.; Löhr, H.F.; Galle, P.R., 2006: Consensus interferon and ribavirin for patients with chronic hepatitis C and failure of previous interferon-alpha therapy. Background: The efficacy of consensus interferon (CIFN), a synthetic IFN with optimised in vitro activity, was assessed in chronic hepatitis C virus (HCV) patients who had failed the pretreatment with interferon-alpha (IFN alpha) and ribavirin. Me...

Risica, P.Markham.; Viner-Brown, S.; Hesser, J., 2006: Obesity and overweight among adults in Rhode Island. Medicine and Health, Rhode Island 89(7): 257-258

Sherrod, Theodore R., 1961: The action of hydroxyzine on the pressor responses to epinephrine and norepinephrine. FED PROC 20(1 Pt 1): 111

Speare, R., 2001: Hot water kills head lice experimentally placed on brushes. International Journal of Dermatology 39(12): 954-956

Foley, R.K.; Kirkaldy-Willis, W.H., 1979: Chronic venous hypertension in the tail of the Wistar rat. Venous hypertension in the extremities has been associated with new bone formation and with degenerative joint disease. The relationship between increased intraosseous pressure and bone remodeling was investigated in the vertebrae of the tail of t...

Bennett, J., 2003: Learning circles: collaborating to promote RN and LPN role enhancement. Recent events in the Newfoundland and Labrador healthcare system, including changes to nursing scope of practice, have had a profound effect on practice environments for direct care registered nurses (RNs) and Licensed practical nurses (LPNs). Thi...

Mazzoni, V., 2001: Catalogue of Auchenorrhycha (Rhynchota Homoptera) of the collection of the Dipartimento di Coltivazione e Difesa delle Specie Legnose G. Scaramuzzi, Section of Agricultural Entomology, University of Pisa. A revision of the Auchenorrhyncha of the entomological collection of the Dept. "C.D.S.L.", Sect. Agricultural Entomology of the University of Pisa, has been done. Some 221 species, belonging to 8 families, have been revised and catalogue...

Yoshikawa, M.; Uchida, E.; Chatani, N.; Kobayashi, H.; Naitoh, Y.; Okuno, Y.; Matsuda, H.; Yamahara, J.; Murakami, N., 1992: Thunberginols C, D, and E, new antiallergic and antimicrobial dihydroisocoumarins, and thunberginol G 3'-O-glucoside and (-)-hydrangenol 4'-O-glucoside, new dihydroisocoumarin glycosides, from Hydrangeae Dulcis Folium. Three dihydroisocoumarins (thunberginols C, D and E), and 2 new dihydroisocoumarin glycosides, named thunberginol G 3'-O-glucoside and (-)-hydrangenol 4'-O-glucoside, were isolated from Hydrangeae Dulcis Folium, the fermented and dried l...

Warner, C.B.; Martin, M.K., 1999: eXpTools: a C++ class library for animation, tachistoscopic presentation, and response timing. The eXpTools Library is a general-purpose tool for developing psychological experiments that combine animation with tachistoscopic presentation. The library's C++ classes and assembly language functions are specialized for the creation of vis...

Olsewski, T., 1985: The agricultural regions of Poland. The variety of locations forming Poland's agricultural production structure are outlined.