Kinetics noncompartmental model

The kinetic parameters of the noncompartmental model are those defined previously for the accessible pool and system. However/ the formulas depend upon the experimental protocol/ especially on the mode of drug administration. In this chapter/ only the canonical inputs will be considered/ such as an intravenous bolus (or multiple boluses) or constant infusion (or multiple constant infusions). References will be given for those interested in more complex protocols. 

If one has pharmacokinetic data and knows that the situation calls for nonlinear kinetics, then compartmental models, no matter how difficult to postulate, are really required. Noncompartmental models cannot deal with the time-varying situation. 

As discussed, the noncompartmental model divides the system into two components an accessible pool and nonaccessible pools. The kinetics of the nonacces-sible pools are lumped into the recirculation-exchange arrows. From this, as has been discussed, we can estimate pharmacokinetic parameters describing the accessible pool and system. 

With the noncompartmental model, there are two kinetic spaces of interest, the sampling or central kinetic space and the peripheral kinetic space. The average length of time that all drug molecules spend in a specific kinetic space is the mean residence time of that kinetic space. 

One of the most common transformations is the natural logarithmic transformation of multiplicative models. Many pharmacokinetic parameters, such as area under the curve (AUC) and maximal concentration, are log-normal in distribution (Lacey et al., 1997), and hence, using the Ln-transformation results in approximate normality. The rationale is as follows (Westlake, 1988). For a drug that has linear kinetics and elimination occurs from the central compartment (the usual assumptions for a noncompartmental analysis) then... 

Plotting the mean data suggested the kinetics of DFMO to be at least biphasic. First, the intravenous data were fit using SAAM II to a 2-compartment model using the noncompartmental estimate for clearance (CL) as the initial value, 1.2 mL/(min/kg). The initial estimates for central volume (VI) and peripheral volume (V2) were divided equally between the noncompartmental estimate for volume of distribution at steady-... 

Cobehi, C., Toffolo, G., and Ferrannini, E. 1984b. A model of glucose kinetics and their control by insuhn. Compartmental and noncompartmental approaches. Math. Biosci. 72 291-315. 

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