Biomaterial Database

Disposition characteristics of coumarin as a function of age in the beagle dog model. 1993

W A Ritschel, and N N Vachharajani

Division of Pharmaceutics and Drug Delivery Systems, College of Pharmacy, University of Cincinnati Medical Center, Ohio.

Coumarin (C, CAS 91-64-5) is a high extraction ratio drug, and its clearance reflects the liver blood flow. The purpose of this study was to investigate the alterations in the pharmacokinetics of C as a function of age, and to evaluate the suitability of beagle dog model to study age dependent changes in the hepatic function. In this longitudinal study, C was administered intravenously to male beagle dogs, ranging in age from < 1 to 15 years. The total clearance decreased significantly from 30.67 +/- 9.58 to 16.61 +/- 2.35 ml/min/kg and the ratio of AUC of glucuronide metabolite to parent drug decreased from 1.26 +/- 0.52 to 0.72 +/- 0.17 in old dogs. No significant changes were observed in apparent volume of distribution and elimination half-life. The changes in clearance of C parallels the observed reduction in the liver blood flow in man, suggesting that the beagle dog appears to be a good model for drug disposition studies in gerontokinetics.

UI	MeSH Term	Description	Entries
D007275	Injections, Intravenous	Injections made into a vein for therapeutic or experimental purposes.	Intravenous Injections,Injection, Intravenous,Intravenous Injection
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
D008102	Liver Circulation	The circulation of BLOOD through the LIVER.	Hepatic Circulation,Circulation, Liver,Circulation, Hepatic
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
D003374	Coumarins	Synthetic or naturally occurring substances related to coumarin, the delta-lactone of coumarinic acid.	1,2-Benzopyrone Derivatives,1,2-Benzopyrones,Coumarin Derivative,Coumarine,1,2-Benzo-Pyrones,Benzopyran-2-ones,Coumarin Derivatives,Coumarines,1,2 Benzo Pyrones,1,2 Benzopyrone Derivatives,1,2 Benzopyrones,Benzopyran 2 ones,Derivative, Coumarin,Derivatives, 1,2-Benzopyrone,Derivatives, Coumarin
D004285	Dogs	The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065)	Canis familiaris,Dog
D006207	Half-Life	The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity.	Halflife,Half Life,Half-Lifes,Halflifes
D000375	Aging	The gradual irreversible changes in structure and function of an organism that occur as a result of the passage of time.	Senescence,Aging, Biological,Biological Aging
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