The determination of the absolute bioavailability for drug substances with long elimination half-lives (with PC-programs for the method of truncated areas).
A survey is given of the methods for the determination of the absolute bioavailability for drug substances with long elimination half-lives. All methods depend on the assumption of linear pharmacokinetics. Emphasis is laid on Urso and Aarons' regression method of truncated areas-under-the-curve (AUC) to obtain estimates of the absolute bioavailability, F, and the absorption rate constant, ka, without obeying the otherwise general rule of following blood or plasma levels for at least three times the terminal half-life. It is shown by simulation when the linear and when the logarithmic trapezoidal rule is to be used for the calculation of the AUC. Two PC-programs for the regression method of truncated areas are presented: one program (SIMF&KA.EXE) simulates, based on tentative pharmacokinetic parameters, whether a blood sampling scheme, together with the precision of the analytical assay, is adequate to obtain accurate and precise estimates of F and ka; the method is insensitive to large variations in the tentative value of the elimination half-life. The other program (ESTF&KA.EXE) provides estimates of F and ka, with standard deviations of the estimates, from empirical data.
Wijnand
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D001682:Biological Availability; D005069:Evaluation Studies as Topic; D017408:Guidelines as Topic / Q000592:standards; D006801:Humans; D009716:Numerical Analysis, Computer-Assisted; D010599:Pharmacokinetics; D012044:Regression Analysis; D015203:Reproducibility of Results; D012986:Software Validation