Biomaterial Database

Relationships between steady-state and single-dose plasma drug concentrations for pharmacokinetic systems with nonlinear elimination. 1989

H Y Cheng, and W J Jusko

Department of Pharmaceutics, School of Pharmacy, State University of New York, Buffalo 14260.

Equations were examined to predict or correlate steady-state (SS) plasma concentrations and single-dose (SD) data for pharmacokinetic systems with various types of input and nonlinear elimination. The effects of variation of the Michaelis-Menten parameters, input rate of drug, or bioavailability on the predictability of steady-state plasma concentrations from single-dose data were demonstrated by computer simulations for a one-compartment model. Use of apparently linear equations with Michaelis-Menten parameters to predict steady-state plasma concentrations from single dose data is adequate only in limiting low single-dose cases. Linear SS versus SD correlations for both intravenous and oral dosing can be observed in population data only when Km is the principal variable; other conditions produce curvilinear behavior. Equations to calculate values of the Michaelis-Menten parameters from dual single-dose and steady-state AUC values are derived and tested for drugs which are intravenously administered. These equations and simulations provide insight into factors determining the relationship between SS and SD AUC for drugs with nonlinear elimination.

UI	MeSH Term	Description	Entries
D007262	Infusions, Intravenous	The long-term (minutes to hours) administration of a fluid into the vein through venipuncture, either by letting the fluid flow by gravity or by pumping it.	Drip Infusions,Intravenous Drip,Intravenous Infusions,Drip Infusion,Drip, Intravenous,Infusion, Drip,Infusion, Intravenous,Infusions, Drip,Intravenous Infusion
D007275	Injections, Intravenous	Injections made into a vein for therapeutic or experimental purposes.	Intravenous Injections,Injection, Intravenous,Intravenous Injection
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