Therapeutic Drug Monitoring

Given the multiple factors that alter drug disposition, measurement of the concentration in body fluids can assist in individualizing therapy with selected drugs. Determination of the concentration of a drug is particularly useful when well-defined criteria are met:

1. A demonstrated relationship exists between the concentration of drug in plasma and the desired therapeutic effect or the toxic effect to be avoided. The range of plasma levels between that required for efficacy and that at which toxicity occurs for a given individual is designated the therapeutic window.

2. There is sufficient variability in plasma level that the level cannot be predicted from the dose alone.

3. The drug produces effects, intended or unwanted, that are difficult to monitor.

4. The concentration required to produce the therapeutic effect is close to the level that causes toxicity (i.e., there is a low therapeutic index).

A clear demonstration of the relation of drug concentration to efficacy or toxicity is not achievable for many drugs; even when such a relationship can be determined, it usually predicts only

FIGURE 5-5 The relation of the therapeutic window of drug concentrations to the therapeutic and adverse effects in the population. Ordinate is linear; abcissa is logarithmic.

Concentration of drug in plasma (ng/mL)

FIGURE 5-5 The relation of the therapeutic window of drug concentrations to the therapeutic and adverse effects in the population. Ordinate is linear; abcissa is logarithmic.

a probability of efficacy or toxicity. In trials of antidepressant drugs, such a high proportion of patients respond to placebo that it is difficult to determine the plasma level associated with efficacy. There is a quantal concentration-response curve for efficacy and adverse effects (Figure 5-5); for many drugs, the concentration that achieves efficacy in all the population may produce adverse effects in some individuals. Thus, a population therapeutic window expresses a range of concentrations at which the Likelihood of efficacy is high and the probability of adverse effects is low. It does not guarantee either efficacy or safety. Therefore, use of the population therapeutic window to adjust dosage of a drug should be complemented by monitoring appropriate clinical and surrogate markers for drug effect.

Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

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