ISSN:
1432-1041
Keywords:
Linear pharmacokinetics
;
ill-posed problem
;
Tikhonov regularization
;
parameter estimation
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
,
Medicine
Notes:
Summary 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 λi and associated coefficients Ci. Least-square fitting procedures are used to estimate the coefficients Ci and the corresponding discrete locations λi on the λ-axes. This work presents an alternative approach. It does not assume that the non-zero coefficients are located at sharply defined values of λ, but that they are represented by a continuous function h(λ), 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”. Regularisation methods have been developed in recent years as suitable tools for the treatment of such ill-posed problems. Application of Tikhonov regularisation 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(λ). The method used is described and the results are compared with those of conventional compartment analysis.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00315312
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