ABC of monitoring drug therapy. Making the most of plasma drug concentration measurements.
Authors: D J Reynolds, J K Aronson
Journal: BMJ (1993)

Criteria that a drug should satisfy for plasma concentration measurements to be useful * Difficulty in interpreting clinical evidenceIn the previous articles in this series we have outlined the principles of of therapeutic or toxic effects monitoring drug therapy by measuring the plasma drug concentration and * A good relation between the plasma drug shown how they can be applied to specific drugs (digoxin, lithium, concentration and the therapeutic or toxic theophylline, phenytoin, aminoglycoside antibiotics, and cyclosporin), for effect, or both which the criteria in the box are sufficiently fulfilled to justify monitoring.* A low toxic:therapeutic ratio * Does not metabolise to important active metabolites Usefulness ofmeasurementWhen the criteria are not rigorously met the regular use ofplasma drug concentration measurements is hard to justify.None the less, measurements are sometimes made for other drugs, including anticonvulsants such as carbamazepine and ethosuximide; antiarrhythmic drugs; tricyclic antidepressants; and methotrexate.These are drugs which fulfil some but not all ofthe criteria.In some circumstances, however, their Indications for measuring plasma | measurement may be helpful (for example, in monitoring compliance).drug concentrations * Monitoring complianceEven for drugs that fulfil the criteria there is some controversy about the * Individualising therapy usefulness of monitoring their plasma concentrations.-during early therapy -during dosage changes Firstly, it has been argued that there is no good evidence that targeting * Diagnosing undertreatment plasma concentrations improves the therapeutic outcome' 2 and that the * Avoiding toxicity hypothesis that it is oftherapeutic value needs to be tested.3These * Diagnosing toxicity arguments ignore the axiom, which implies that there is a better relation * Monitoring and detecting drug between concentration and effect than between dose and effect, implying interactions that it should be possible to improve therapy with a drug by monitoring its * Guiding withdrawal of therapy plasma concentrations.In practice, however, the benefit to be gained is likely to be small when the drug does not fulfil the necessary criteria.There is certainly a need for prospective studies to determine the benefit of monitoring drug concentrations, though there would be considerable practical and ethical difficulties in designing such studies.Secondly, it is argued that the value ofthe technique is reduced by problems in defining therapeutic ranges-for example, when there are ,PL d conditions that alter a drug's pharmacodynamic effects.3But this argument merely emphasises the need for proper interpretation of plasma drug concentrations in these conditions.Thirdly, it has been said that too often it is the plasma concentration which is treated rather than the patient4 and that much monitoring is rendered useless by, for example, inappropriate timing of sampling.'That this is so is evidence that plasma drug concentration monitoring is being misused rather than that it is ofno use.