Simple method for the estimation of absorption rate constant(ka) after oral administration. 1998

I Mahmood
Office of clinical Pharmacology and Biopharmaceutics, Food and Drug Administration, Rockville, MD 20852, USA.

This article describes a simple method for the estimation of absorption rate constant (ka ) after oral administration and compares the proposed method with some of the existing methods. The proposed method is based on a previous work of Urso and Aarons known as the regression method of truncated areas for the estimation of absolute bioavailability for drugs with a long elimination half-life. The following equation was used to estimate ka : Y(t) = ka. F - ka. X(t). Simple linear regression of Y(t) on X(t) results in a straight line with a slope of -ka, intercept on y-axis of ka F, and abscissa intercept F (absolute bioavailability). Different sets of plasma concentration versus time data for a hypothetical drug were generated by simulation. The estimated ka from the proposed method was compared with the Wagner-Nelson, Loo-Riegelman, and statistical moments methods. The results of this study indicated that the proposed regression method performed satisfactorily for a hypothetical drug that follows a one-compartment or two-compartment model with short or long half-life when tested under variable conditions (different absorption and elimination rate constants). The regression method of truncated areas can be used for the accurate estimation of ka for both short and long half-life drugs.

UI MeSH Term Description Entries
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
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
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
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000042 Absorption The physical or physiological processes by which substances, tissue, cells, etc. take up or take in other substances or energy.
D000284 Administration, Oral The giving of drugs, chemicals, or other substances by mouth. Drug Administration, Oral,Administration, Oral Drug,Oral Administration,Oral Drug Administration,Administrations, Oral,Administrations, Oral Drug,Drug Administrations, Oral,Oral Administrations,Oral Drug Administrations

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