Therapeutic Drug Monitoring: Will It Ever Be a Useful Clinical Tool?

By Brian Boyle, MD

Therapeutic drug monitoring (TDM) has received significant attention over the past few years, but has yet to move into common clinical use. Several problems have held back TDM and these were discussed, along with potential solutions, by David Burger of University Medical Centre St Radboud in the Netherlands.

Dr. Burger listed areas where TDM may be of particular use such as virological failure, drug intoxication, concerns regarding drug-drug interactions, and nonadherence. He admitted, however, that to this point there has been no consensus among pharmacologists about the best way of using TDM of antiretroviral agents. He pointed out that there are several studies now underway that will give us information how to use TDM in the near future.

During the plenary session, Dr. Burger listed some of his "commandments" regarding TDM and discussed their implications. This discussion included the following points:

(1) The large variability in accuracy of doing TDM measurements by different laboratories requires that assays need to be optimized and validated.

(2) The person doing TDM must have adequate information so that adequate advice can be given (e.g., patient weight, indication for TDM, time between last dose and time of sampling, etc.).

(3) Sampling of troughs is probably the most appropriate use of TDM since it is probably the best indicator of viral efficacy, but this remains uncertain regarding some of the antiretrovirals.

(4) The need to make sure that there is adequate information regarding the timing of dosing; without this the data from TDM are virtually worthless.

(5) The need to know critical levels when sampling for toxicity. Peak levels most likely related to toxicity, but information in this area is limited.

(6) Know the therapeutic range of the medication, but again there is not a lot of information.

(7) Recognize the difference between treatment naïve and experienced patients, since different drug levels may be important in these patients, especially if resistance is present.

(8) Recognize hat TDM is a probabilistic concept, not a guarantee for efficacy or toxicity.

(10)Use the inhibitory quotient (IQ) concept, although we need more information about these before we can use effectively. The best way to use TDM is to consult an expert on resistance and IQ, otherwise value of data may be extremely limited.

(11)Plan for the appropriate management of abnormal levels. Pay attention to incorrect dosing, and whether the patient is taking the medication according to food restrictions or if there are problems with drug interactions or non-adherence.

(12) Talk about and act to correct non-adherence. Recognize that a detectable or appropriate drug level at on time point is not necessarily reflective of overall adherence. Further, evaluate your adherence intervention and see that it is effective.

(13) Consider the frequency of TDM and recognize that it is likely that it must be done more than once, with intermittent monitoring, to be effective. Dr. Burger pointed out that further information can be obtained at www.hivpharmacology.com.

It appears to be his opinion, shared by many in attendance at the session, that TDM is going to be a valuable tool for clinicians once some of the issues surrounding it are resolved.

11/22/02

Reference
D Burger. Therapeutic drug monitoring - does it make a difference? 6th International Congress on Drug Therapy in HIV Infection. Plenary session 8.1. November 17-21, 2002. Glasgow, UK.