Simple Method for the Estimation of Absorption Rate Constant (ka) After Oral Administration

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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 kaF, 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.

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