The use of a sum of inverse Gaussian functions to describe the absorption profile of drugs exhibiting complex absorption.
OBJECTIVE
The aim of this study was to evaluate the utility of a parametric deconvolution method using a sum of inverse Gaussian functions (IG) to characterize the absorption and concentrations vs. time profile of drugs exhibiting complex absorption.


METHODS
For a linear time-invariant system the response, Y(t), following an arbitrary input function I(t), is the convolution of I(t) with the disposition function, H(t), of the system: [Formula: see text]. The method proposed uses a sum of n inverse Gaussian functions to characterize I(t). The approach was compared with a standard nonparametric method using linear splines. Data were provided from previously published studies on two drugs (hydromorphone and veralipride) showing complex absorption and analyzed with NONMEM.


RESULTS
A satisfactory fit for hydromorphone and veralipride data following oral administration was achieved by fitting a sum of two or three IG functions. The predictions of the input functions were very similar to those using linear splines.


CONCLUSIONS
The use of a sum of IG as opposed to nonparametric functions, such as splines, offers a simpler implementation, a more intuitive interpretation of the results, a built-in extrapolation, and an easier implementation in a population context. Disadvantages are an apparent greater sensitivity to initial value estimates (when used with NONMEM).
Csajka
Chantal
C
Department of Biopharmaceutical Sciences, University of California, San Francisco, California 94143, USA.
Drover
David
D
Verotta
Davide
D
D000465:Algorithms; D001682:Biological Availability; D004091:Hydromorphone / Q000737:chemistry; D007408:Intestinal Absorption / Q000502:physiology*; D016014:Linear Models; D015233:Models, Statistical; D009294:Narcotics / Q000737:chemistry; D016011:Normal Distribution; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D018709:Statistics, Nonparametric; D013469:Sulpiride / Q000031:analogs & derivatives / Q000737:chemistry
D009294:Narcotics; D004364:Pharmaceutical Preparations; D013469:Sulpiride; D004091:Hydromorphone; C027429:veralipride