Two Compartment Model

Compounds exhibiting kinetics described by a two-compartment model have a log concentration-time profile that is biphasic in nature (see Fig. 1.7).

1.3.2.1 Intravenous Dosing k - first-order elimination rate constant (units of time-1)

k12 - intercompartment rate constant from central to peripheral compartment (units of time-1)

k21 - intercompartment rate constant from peripheral to central compartment (units of time-1)

Figure 1.7. Two-compartment model following a single intravenous dose.

Concentration following an intravenous dose can be calculated using the following equation:

where

C is concentration a is distribution rate constant b is terminal elimination rate constant A is y-axis intercept for distribution phase B is y-axis intercept for elimination phase t is time

Relationships of a, b, A, and B (macroconstants) to k12, k21, and k (microconstants) are as follows:

Vc(b

where VC is the volume of the central compartment.

Many of these parameters can be estimated using commercial pharmacokinetic software such as WinNonlin® and Kinetica®. For more detailed information about compartmental models, please refer to references at the end of this chapter.

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