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A Note on Population Analysis of Dissolution‐Absorption Models Using the Inverse Gaussian Function
Author(s) -
Wang Jian,
Weiss Michael,
D'Argenio David Z.
Publication year - 2008
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270008315956
Subject(s) - inverse , function (biology) , gaussian , population , inverse gaussian distribution , mathematics , dissolution , absorption (acoustics) , statistics , econometrics , statistical physics , chemistry , physics , mathematical analysis , medicine , computational chemistry , distribution (mathematics) , optics , biology , genetics , environmental health , geometry
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.