ISSN:
1573-8744
Keywords:
pharmacokinetics
;
perfusion models
;
sampling
;
parameter estimation
;
computer program
;
Org GB 94
;
mianserin
;
Org GC 94
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
Notes:
Abstract A mathematical treatment of the influence of sampling on drug kinetics in liver perfusion is presented. Based on the derived equations, a Fortran IV computer program (PERFUS) is given, by which the time course of drug concentrations can be simulated for any sampling scheme. The simulations show that the withdrawal of large samples from the reservoir, i.e., larger than 5% of the reservoir volume, results in substantially biased parameters for drugs that are rapidly distributed and/or metabolized. For the fitting of empirical data, a Fortran IV computer program is given, based on BMDX85 nonlinear least squares by Gauss-Newton iterations. This program (PERFIT) estimates model parameters corrected as if no sampling had occurred, no matter how distorted the drug disappearance curve mày be as a result of sampling or due to degeneration of the two-compartment model into a one-compartment model. The conditions under which this degeneration occurs are discussed.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF01061695
