Pharmacokinetic model equations for the one- and two-compartment models with first-order processes in which the absorption and exponential elimination or distribution rate constants are equal. 1988

H P Wijnand
Organon Scientific Development Group, Oss, The Netherlands.

In fitting the one-compartment open model with first-order processes to empirical data, it has frequently been found for single-dose administration that the absorption and elimination rate constants approach each other. If these rate constants tend to be equal, such combinations are impossible to solve with the general model equation. In 1968, Dost published a special model function by which the problems associated with the general model function can be circumvented. No solution, however, has been published for multiple-dose functions with the one-compartment model in which the absorption and elimination rate constants are equal. For a two-compartment open model with first-order processes, similar problems arise if the absorption and exponential distribution rate constants approach each other. Although this type of problems is often encountered in pharmacokinetic curve-fitting to empirical data, no exact solution has been published. Equations are given for multiple-dose administration with the one-compartment open model in which the absorption and elimination rate constants are equal, and for single-dose and multiple-dose administration with the two-compartment open model in which the absorption and exponential distribution rate constants are equal. Included are criteria to decide whether the new or the classical model functions should be applied in the case of a two-compartment open model.

UI MeSH Term Description Entries
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
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

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