Why do therapeutic drug monitoring
Although pharmacokinetic differences in drug handling between patients produce wide variabilities in serum drug concentration measurements, dosage adjustments are generally only required if there is serious organ damage, such as severe renal impairment. Dosage requirements of individual patients can also vary significantly if a drug has a narrow therapeutic index. In such circumstances, dose titration based on the response to the drug would be ideal. For example, the dose of warfarin can be adjusted according tothe international normalised ratio.
However, for other drugs, therapeutic effects are not easily measured and toxic effects may be non-specific. In these circumstances, assuming the relationship between the drug concentration and the response is known, measuring the concentration of the drug in the patient’s blood can provide useful information.
When to collect a sample
Drug concentrations are usually measured in whole blood or serum, although saliva, which gives a measure of the unbound drug concentration, may be a useful alternative when blood samples are difficult to collect. For example, measuring phenytoin concentrations in children.
Unlike most sampling for biochemistry and haematology, the timing of the sample (in relation to the previous dose) influences the interpretation of a drug concentration measurement. For most drugs, the relationship between response and concentration (and, therefore, target concentrations) are based on steady-state samples (see PJ, 19 June, p769) taken at specific times after the dose. “Trough” concentrations (at the end of the dosage interval) are commonly used for anticonvulsant drugs, whereas “peak” concentration measurements may be useful for some antibiotics. The relationship between concentration and response is sometimes determined by the time above a threshold value (for example, the minimum inhibitory concentration [MIC]).
Responses to some anticancer drugs and immunosuppressants have been related to the patient’s overall exposure to the drug, as measured by the area under the concentration-time curve (AUC). The AUC takes into account both the dose and the patient’s ability to clear the drug. So:
AUC = dose ÷ clearance
Figure 1 illustrates that, despite being given the same dose, a patient whose clearance is 4L/h has an overall exposure to the drug that is twice that of a patient whose clearance is 8L/h. Note, however, that in this case their trough concentration measurements are similar. This means that if only trough samples are taken, both patients would appear to have the same dosage requirements. Similar problems occur when there is wide variability in bioavailability.
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Citation: The Pharmaceutical Journal URI: 10997177
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