title: The use of a physiologically based pharmacokinetic model to evaluate deconvolution measurements of systemic absorption.
abstract: BACKGROUND
  An unknown input function can be determined by deconvolution using the systemic bolus input function (r) determined using an experimental input of duration ranging from a few seconds to many minutes. The quantitative relation between the duration of the input and the accuracy of r is unknown. Although a large number of deconvolution procedures have been described, these routines are not available in a convenient software package.
  
  
  METHODS
  Four deconvolution methods are implemented in a new, user-friendly software program (PKQuest, http://www.pkquest.com). Three of these methods are characterized by input parameters that are adjusted by the user to provide the "best" fit. A new approach is used to determine these parameters, based on the assumption that the input can be approximated by a gamma distribution. Deconvolution methodologies are evaluated using data generated from a physiologically based pharmacokinetic model (PBPK).
  
  
  CONCLUSIONS
  The 11-compartment PBPK model is accurately described by either a 2 or 3-exponential function, depending on whether or not there is significant tissue binding. For an accurate estimate of r the first venous sample should be at or before the end of the constant infusion and a long (10 minute) constant infusion is preferable to a bolus injection. For noisy data, a gamma distribution deconvolution provides the best result if the input has the form of a gamma distribution. For other input functions, good results are obtained using deconvolution methods based on modeling the input with either a B-spline or uniform dense set of time points.
authors.affiliation: Department of Physiology University of Minnesota, Minneapolis, MN 55455, USA. levit001@umn.edu
authors.forename: David G
authors.initials: DG
authors.lastname: Levitt
mesh_terms: D000042:Absorption; D000465:Algorithms; D001682:Biological Availability; D003198:Computer Simulation; D006801:Humans; D008954:Models, Biological; D004364:Pharmaceutical Preparations; D010599:Pharmacokinetics; D012107:Research Design; D014018:Tissue Distribution
chemical_list: D004364:Pharmaceutical Preparations