Therapeutic drug monitoring
This is a clinical service available to physicians when a patient is being prescribed a drug (a) that has a relatively small therapeutic window and (b) where the consequences of drug concentrations falling below the minimum effective concentration, or exceeding the maximum tolerated concentration of the therapeutic window, are serious. In addition, monitoring is most often done when the patient suffers from a condition that might make predicting the steady state concentration difficult – for example, a disease condition that alters the degree of drug absorption. Plasma samples may be taken at several time points early in the dosing regimen and drug concentrations can be analysed by clinical pharmacists or clinical pharmacologists to predict whether the steady state concentration that will eventually be reached will lie within or outside the therapeutic window. Patient-specific advice on alterations to the dosing regimen can then be offered in order to avoid problems that would otherwise occur.
Monitoring is more routinely done once steady state has been reached, to ensure target concentrations have been achieved and to give warning of any change in the patient’s handling of the drug over time. Again, this would allow dosing adjustments to be made before problems become evident, or before they result in more serious consequences.
In a repeated administration dosing regimen, the point during the dosing cycle at which plasma is sampled and drug (or metabolite) quantified depends upon the drug and upon the clinical reason for monitoring plasma concentrations. Measurement of peak (Cmax) concentrations requires some knowledge of absorption and distribution pharmacokinetics while trough (Cmin) concentrations are obtained from samples taken immediately before the next scheduled drug dose. For drugs with short half-lives, both peak and trough concentrations may be determined to obtain a clear understanding of the profile at steady state, while trough concentrations are often sufficient to understand profiles for drugs with longer half-lives. Trough concentrations are the most reproducible of the measurements that can be made.
Where it is necessary to ensure that plasma concentrations of drug do not fall below a minimum effective concentration, such as with some antibiotics, trough concentrations are usually determined. On the other hand, if toxicity at higher concentrations is the major concern, peak concentrations are more likely to be quantified.
