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Pharmacokinetic model identification and parameter estimation as an ill-posed problem.

Abstract：

:For model identification and parameter estimation in the framework of linear pharmacokinetics it is most often assumed that the disposition function is a finite sum of exponential functions with time constants lambda i and associated coefficients Ci. Least-square fitting procedures are used to estimate the coefficients Ci and the corresponding discrete locations lambda i on the lambda-axes. This work presents an alternative approach. It does not assume that the non-zero coefficients are located at sharply defined values of lambda, but that they are represented by a continuous function h(lambda), the spectrum of the disposition function. This turns the non-linear least-square problem into a linear problem, which is known to be as so-called "ill-posed". Regularization methods have been developed in recent years as suitable tools for the treatment of such ill-posed problems. Application of Tikhonov regularization to the case of the bolus kinetics of propofol in 8 volunteers is demonstrated. In 7 of the 8 cases a spectrum with 4 to 5 peaks was found, and in one volunteer there were only 2 peaks. All spectra with more than 2 peaks showed negative values of h(lambda). The method used is described and the results are compared with those of conventional compartment analysis.

journal_name

Eur J Clin Pharmacol

journal_title

European journal of clinical pharmacology

authors

Schwilden H,Honerkamp J,Elster C

doi

10.1007/BF00315312

subject

Has Abstract

pub_date

1993-01-01 00:00:00

pages

545-50

issue

6

eissn

0031-6970

issn

1432-1041

journal_volume

45

pub_type

杂志文章

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