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A Note on Population Analysis of Dissolution-Absorption Models Using the Inverse Gaussian Function

From the Department of Biomedical Engineering, University of Southern California, Los Angeles (Dr Wang, Dr D'Argenio) and the Section of Pharmacokinetics, Department of Pharmacology, Martin Luther University, Halle-Wittenberg, Germany (Dr Weiss).

Because conventional absorption models often fail to describe plasma concentration–time profiles following oral administration, empirical input functions such as the inverse Gaussian function have been successfully used. The purpose of this note is to extend this model by adding a first-order absorption process and to demonstrate the application of population analysis using maximum likelihood estimation via the EM algorithm (implemented in ADAPT 5). In one example, the analysis of bioavailability data of an extended-release formulation, as well as the mean dissolution times estimated in vivo and in vitro with the use of the inverse Gaussian function, is well in accordance, suggesting that the inverse Gaussian function indeed accounts for the in vivo dissolution process. In the other example, the kinetics of trapidil in patients with liver disease, the absorption/dissolution parameters are characterized by a high interindividual variability. Adding a first-order absorption process to the inverse Gaussian function improved the fit in both cases.

Key Words: Bioavailability • drug absorption • extended release • population pharmacokinetics • ADAPT

Address for reprints: David D'Argenio, PhD, Department of Biomedical Engineering, University of Southern California, 1042 Downey Way, DRB 140, Los Angeles, CA 90089; e-mail: dargenio{at}bmsr.usc.edu.

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