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Fitting discordant models among individuals

Deterministic simulation will be used to illustrate the effect of fitting a less complex to model to data arising from a more complex model. Concentrationtime data were simulated from a 3-compartment model with the following parameters CL = 1.5 Q2 = 0.15 Q3 = 0.015 VI = 1, V2 = 0.5 V3 = 0.25. A bolus unit dose of 100 was injected into the central compartment (VI). A total of 50 samples were collected equally spaced for 48-time units. The data are shown in Fig. 3.15 and clearly demonstrate triphasic elimination kinetics. Now suppose the LLOQ of the assay was 0.01. Data above this line are consistent with biphasic elimination kinetics. What hap- [Pg.122]

This simple simulation can be expanded to different combinations of parameters, using a 1-compartment model to fit data simulated through a 2-compartment model, or even expanding the model to include an absorption compartment. The end result is the same— all parameters related to the central compartment will be unbiased estimates of the true values, whereas parameters related to the peripheral compartments will be biased. In going back to the original problem, it is okay to report data from individuals having fewer compartments but the limitations of the results and the interpretation of the results must be kept in mind. [Pg.122]

The choice of computer processor may also have an impact on the results of fitting a nonlinear regression model. Wakelkamp solved an indirect response model described by three differential equations on four computers with different central processing units using the [Pg.123]

3 Although Adapt II is free, in order to use the program, a Fortran compiler must be available to compile the Adapt II source code. All the supported compilers for the most recent version (Version 4), however, are commercial and must be bought for a fee. [Pg.123]

Pharmacokinetic and pharmacodynamic modeling is not something that is taught, but something that is caught, and while this chapter is a didactic presentation of nonlinear modeling, only through practical experience and trial and error will the real nuances of how these variables interact will be understood. [Pg.123]


See other pages where Fitting discordant models among individuals is mentioned: [Pg.121]    [Pg.121]   
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