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Figure 18.11 Typical concentration-time plot for two-compartment model. The systemic compartment typically represents blood concentration. The peripheral compartment can represent another tissue or organ, such as the brain or muscle. C and V are the concentration and volume, respectively, of the compartments. In this simulation ke, Kp, and V2 = 1.0, and Vi = 3.0.

Figure 18.11 Typical concentration-time plot for two-compartment model. The systemic compartment typically represents blood concentration. The peripheral compartment can represent another tissue or organ, such as the brain or muscle. C and V are the concentration and volume, respectively, of the compartments. In this simulation ke, Kp, and V2 = 1.0, and Vi = 3.0.

effects would take longer to appear. Biotransformation reactions are neglected in these examples. If the system behaved more like a one-compartment model, the toxicant would be cleared in a depuration process similar to that shown in the second part of Figure 18.8.

Figure 18.12 shows a similar plot for the second two cases. Intermittent exposure results in higher peak concentrations, which may cause a greater effect either if the effect is concentration associated or if there is a threshold. On the other hand, the periodic decrease in concentration may enable repair mechanisms to eliminate previous damage. This has been observed in exposing rats to ozone. A concentration that caused pulmonary edema when applied continuously had no effect when applied intermittently. However, if damage is cumulative, the integral of both curves will be similar, as will be their effect. An example is the application of organophosphate pesticides, which cumulatively deplete acetocholinesterase. There is a repair mechanism, in the form of hydrolysis of the enzyme-OP compound and replacement of the enzyme, but it can be overwhelmed at moderate doses.

Time

Figure 18.13 Effect of differing pharmacokinetics on the time course of concentration in an organism. ke, Kp, and V1 = 1.0, and V2 = 1-0 or 0.1 as indicated.

Finally, the same dosing regimen could result in very different concentration-time relationships, depending on the pharmacokinetics involved. Slow adsorption and elimination or the presence of a large storage compartment could smooth out changes in concentration. In Figure 18.13 the concentration in the peripheral compartment does not vary greatly when the two compartments have the same volume (V1 = V2 = 1.0). But when the peripheral compartment is much smaller (V2 = 0.1), large concentration swings occur.

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