Biomaterial Database

A physiologically based pharmacokinetic model incorporating dispersion principles to describe solute distribution in the perfused rat hindlimb preparation. 1997

R E Oliver, and A C Heatherington, and A F Jones, and M Rowland

School of Pharmacy and Pharmaceutical Sciences, University of Manchester, England.

A physiologically based pharmacokinetic model incorporating dispersion principles has been developed to describe outflow data from the isolated perfused rat hindlimb preparation, for the three reference markers 14C-sucrose, 14C-urea, and 3H-water and three 14C-labeled 5-n-alkyl-5-ethyl barbiturates; the methyl, butyl, and nonyl homologues. Also 51Cr-RBC and 125I-albumin were studied. The model consists of four parallel components representing each of the tissues comprising the hindlimb: skeletal muscle, skin, bone, and adipose. Attempts to simplify the model by using the principle of tissue lumping were made by examining the tissue equilibration rate constant k tau for each of respective tissues for each compound. It was found that simplification was only possible in the case of 3H-water data. The model took into account a possible shunting component in the skin tissue and incomplete mass but not volumetric recovery from the system. The dispersion model characterizes the relative spreading of solute on transit through a tissue bed by a dimension-less parameter DN. The estimated dispersion numbers (DN) obtained were in the region of 2.7-4.72, 8.39-15.54, 0.61-2.74, and 6.02-14.0 for skeletal muscle, skin, bone, and adipose, respectively, and were independent of the compound studied. These values are much larger than the range reported in the literature for hepatic outflow data, DN = 0.2-0.5, and suggest a greater heterogeneity of vascular flow in the different component tissues of the rat hindlimb.

UI	MeSH Term	Description	Entries
D008433	Mathematics	The deductive study of shape, quantity, and dependence. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)	Mathematic
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
D010477	Perfusion	Treatment process involving the injection of fluid into an organ or tissue.	Perfusions
D010599	Pharmacokinetics	Dynamic and kinetic mechanisms of exogenous chemical DRUG LIBERATION; ABSORPTION; BIOLOGICAL TRANSPORT; TISSUE DISTRIBUTION; BIOTRANSFORMATION; elimination; and DRUG TOXICITY as a function of dosage, and rate of METABOLISM. LADMER, ADME and ADMET are abbreviations for liberation, absorption, distribution, metabolism, elimination, and toxicology.	ADME,ADME-Tox,ADMET,Absorption, Distribution, Metabolism, Elimination, and Toxicology,Absorption, Distribution, Metabolism, and Elimination,Drug Kinetics,Kinetics, Drug,LADMER,Liberation, Absorption, Distribution, Metabolism, Elimination, and Response
D004912	Erythrocytes	Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing HEMOGLOBIN whose function is to transport OXYGEN.	Blood Cells, Red,Blood Corpuscles, Red,Red Blood Cells,Red Blood Corpuscles,Blood Cell, Red,Blood Corpuscle, Red,Erythrocyte,Red Blood Cell,Red Blood Corpuscle
D006614	Hindlimb	Either of two extremities of four-footed non-primate land animals. It usually consists of a FEMUR; TIBIA; and FIBULA; tarsals; METATARSALS; and TOES. (From Storer et al., General Zoology, 6th ed, p73)	Hindlimbs
D000418	Albumins	Water-soluble proteins found in egg whites, blood, lymph, and other tissues and fluids. They coagulate upon heating.	Albumin
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
D051381	Rats	The common name for the genus Rattus.	Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus
D018482	Muscle, Skeletal	A subtype of striated muscle, attached by TENDONS to the SKELETON. Skeletal muscles are innervated and their movement can be consciously controlled. They are also called voluntary muscles.	Anterior Tibial Muscle,Gastrocnemius Muscle,Muscle, Voluntary,Plantaris Muscle,Skeletal Muscle,Soleus Muscle,Muscle, Anterior Tibial,Muscle, Gastrocnemius,Muscle, Plantaris,Muscle, Soleus,Muscles, Skeletal,Muscles, Voluntary,Skeletal Muscles,Tibial Muscle, Anterior,Voluntary Muscle,Voluntary Muscles