Biomaterial Database

Local disposition of a new xanthine oxidase/xanthine dehydrogenase inhibitor, BOF-4272, in rat liver. 1994

M Nishimura, and K Yamaoka, and H Yasui, and S Naito, and T Nakagawa

Faculty of Pharmaceutical Sciences, Kyoto University, Japan.

The local hepatic disposition of BOF-4272, a newly developed xanthine oxidase (XO)/xanthine dehydrogenase (XDH) inhibitor, was evaluated in the rat perfusion system following pulse input of the drug into the portal vein. The elution time profiles from the liver into the hepatic vein were analyzed by dispersion models. The disposition of BOF-4272 through the rat liver was represented by a two-compartment dispersion model based on the Akaike's Information Criterion (AIC). The area under the concentration time curve (aucH) of BOF-4272 was proportional to the dosing amount, and the mean transit time was constant from 62.5 up to 500 micrograms/liver, which demonstrates that the local hepatic disposition of BOF-4272 is linear in this dosing range. The local disposition parameters were precisely estimated at the dosing amount of 250 micrograms/liver using several rats. These parameters in the dispersion model were correlated to the local moment characteristics. The hepatic recovery ratio (FH) was 22.8 +/- 3.2% and the mean transit time (tH) was 0.112 +/- 0.008 min, which show that the influx of BOF-4272 into the liver is efficiently large.

UI	MeSH Term	Description	Entries
D008099	Liver	A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.	Livers
D008297	Male		Males
D008954	Models, Biological	Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.	Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D009929	Organ Size	The measurement of an organ in volume, mass, or heaviness.	Organ Volume,Organ Weight,Size, Organ,Weight, Organ
D010477	Perfusion	Treatment process involving the injection of fluid into an organ or tissue.	Perfusions
D001835	Body Weight	The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms.	Body Weights,Weight, Body,Weights, Body
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D013056	Spectrophotometry, Ultraviolet	Determination of the spectra of ultraviolet absorption by specific molecules in gases or liquids, for example Cl2, SO2, NO2, CS2, ozone, mercury vapor, and various unsaturated compounds. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)	Ultraviolet Spectrophotometry
D014227	Triazines	Heterocyclic rings containing three nitrogen atoms, commonly in 1,2,4 or 1,3,5 or 2,4,6 formats. Some are used as HERBICIDES.	Triazine,Benzotriazines
D014968	Xanthine Dehydrogenase	An enzyme that catalyzes the oxidation of XANTHINE in the presence of NAD+ to form URIC ACID and NADH. It acts also on a variety of other purines and aldehydes.	Purine Hydroxylase I,Xanthine Oxidoreductase,Dehydrogenase, Xanthine,Oxidoreductase, Xanthine