Pharmacodynamic Variability

Individuals vary in the magnitude of their response to the same concentration of a single drug or to similar drugs, and a given individual may not always respond in the same way to the same drug

FIGURE 5-3 The Log concentration—effect relationship. Representative log concentration-effect curve illustrating its four characterizing variables. Here, the effect is measured as a function of increasing drug concentration in the plasma. Similar relationships also can be plotted as a function of the dose of drug administered. These plots are referred to as dose-effect curves. (See text for further discussion.)

FIGURE 5-3 The Log concentration—effect relationship. Representative log concentration-effect curve illustrating its four characterizing variables. Here, the effect is measured as a function of increasing drug concentration in the plasma. Similar relationships also can be plotted as a function of the dose of drug administered. These plots are referred to as dose-effect curves. (See text for further discussion.)

concentration. A concentration-effect curve applies only to a single individual at one time or to an average individual. The intersecting brackets in Figure 5-3 indicate that an effect of varying intensity will occur in different individuals at a specified drug concentration or that a range of concentrations is required to produce an effect of specified intensity in all patients.

Attempts have been made to define and measure individual "sensitivity" to drugs in the clinical setting, and progress has been made in understanding some of the determinants of sensitivity to drugs that act at specific receptors. Drug responsiveness may change because of disease or because of previous drug administration. Receptors are dynamic, and their concentration and function may be up- or down-regulated by endogenous and exogenous factors.

Data on the association of drug levels with efficacy and toxicity must be interpreted in the context of the pharmacodynamic variability in the population (e.g., genetics, age, disease, and other drugs). The variability in pharmacodynamic response in the population may be analyzed by constructing a quantal concentration-effect curve (Figure 5-4A).

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