Biomaterial Database

A method of determining the in vivo drug release rate constant of sustained-release preparation. 1995

H Sun, and M S Chow

Drug Information Center, Hartford Hospital, CT, USA.

Assuming a one-compartment model and first-order processes for drug release, absorption, and elimination, a new equation to describe the fraction of drug to be absorbed (1-Ft) for a sustained-release product is derived. Based on this equation, when In(1-Ft) vs. time is plotted, the slopes yield the drug release rate constant (Kr), the drug absorption rate constant (Ka), and two intercepts that are a mixed function of Ka, Kr, and the fraction of sustained-release (Fs). The accuracy of this equation to generate pharmacokinetic parameters, such as Ka, Kr, Fs, and the bioavailability-volume of distribution ratio (FD/V) was tested by fitting this equation to multiple simulated plasma concentration-time data (5 sets errorless and 75 sets errant data). The absolute percentage error of Ka and FD/V estimated by this equation is much less than that of traditional polyexponential equation, whereas the absolute percentage error of Kr estimated by this equation is statistically significantly less than that of traditional polyexponential equation. Furthermore, with this equation, it is easier to estimate Fs than with traditional equation. An application of this equation in generating these parameters is illustrated for a quinidine sustained-release dosage form-quinidex.

UI	MeSH Term	Description	Entries
D007408	Intestinal Absorption	Uptake of substances through the lining of the INTESTINES.	Absorption, Intestinal
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
D011802	Quinidine	An optical isomer of quinine, extracted from the bark of the CHINCHONA tree and similar plant species. This alkaloid dampens the excitability of cardiac and skeletal muscles by blocking sodium and potassium currents across cellular membranes. It prolongs cellular ACTION POTENTIALS, and decreases automaticity. Quinidine also blocks muscarinic and alpha-adrenergic neurotransmission.	Adaquin,Apo-Quinidine,Chinidin,Quincardine,Quinidex,Quinidine Sulfate,Quinora,Apo Quinidine,Sulfate, Quinidine
D012044	Regression Analysis	Procedures for finding the mathematical function which best describes the relationship between a dependent variable and one or more independent variables. In linear regression (see LINEAR MODELS) the relationship is constrained to be a straight line and LEAST-SQUARES ANALYSIS is used to determine the best fit. In logistic regression (see LOGISTIC MODELS) the dependent variable is qualitative rather than continuously variable and LIKELIHOOD FUNCTIONS are used to find the best relationship. In multiple regression, the dependent variable is considered to depend on more than a single independent variable.	Regression Diagnostics,Statistical Regression,Analysis, Regression,Analyses, Regression,Diagnostics, Regression,Regression Analyses,Regression, Statistical,Regressions, Statistical,Statistical Regressions
D003692	Delayed-Action Preparations	Dosage forms of a drug that act over a period of time by controlled-release processes or technology.	Controlled Release Formulation,Controlled-Release Formulation,Controlled-Release Preparation,Delayed-Action Preparation,Depot Preparation,Depot Preparations,Extended Release Formulation,Extended Release Preparation,Prolonged-Action Preparation,Prolonged-Action Preparations,Sustained Release Formulation,Sustained-Release Preparation,Sustained-Release Preparations,Timed-Release Preparation,Timed-Release Preparations,Controlled-Release Formulations,Controlled-Release Preparations,Extended Release Formulations,Extended Release Preparations,Slow Release Formulation,Sustained Release Formulations,Controlled Release Formulations,Controlled Release Preparation,Controlled Release Preparations,Delayed Action Preparation,Delayed Action Preparations,Formulation, Controlled Release,Formulations, Controlled Release,Prolonged Action Preparation,Release Formulation, Controlled,Release Formulations, Controlled,Sustained Release Preparation,Timed Release Preparation,Timed Release Preparations