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A note on population analysis of dissolution-absorption models using the inverse Gaussian function.

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 absorp...

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Published in:Journal of Clinical Pharmacology Vol. 48; no. 6; pp. 719 - 726
Main Authors: Wang J, Weiss M, D'Argenio DZ
Format: equations & formulas research tables/charts Journal Article
Published: Wiley-Blackwell Jun2008
Online Access:View this record in EBSCOhost
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      dt: Jun2008
      vid: 48
      iid: 6
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      pub: Wiley-Blackwell
      place: Malden, Massachusetts
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        atl: A note on population analysis of dissolution-absorption models using the inverse Gaussian function.
      aug:
        au:
          Wang J
          Weiss M
          D'Argenio DZ
        affil: Department of Biomedical Engineering, University of Southern California, 1042 Downey Way, DRB 140, Los Angeles, CA 90089; dargenio@bmsr.usc.edu.
      sug:
        subj:
          Absorption
          Biological Availability
          Delayed-Action Preparations
          Drugs Pharmacokinetics
          Drug Design
          Funding Source
          Human
      ab: 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.
      pubtype: Academic Journal
      doctype:
        equations & formulas
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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