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.

Medienart:

Artikel

Erscheinungsjahr:

1992

Erschienen:

1992

Enthalten in:

Zur Gesamtaufnahme - volume:39

Enthalten in:

Computer methods and programs in biomedicine - 39(1992), 1-2 vom: 28. Sept., Seite 61-73

Sprache:

Englisch

Beteiligte Personen:

Wijnand, H P [VerfasserIn]

Themen:

Journal Article

Anmerkungen:

Date Completed 17.06.1993

Date Revised 11.09.2019

published: Print

Citation Status MEDLINE

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM012836214