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16 - Therapeutic drug monitoring

Published online by Cambridge University Press:  23 December 2009

By
Stephen C. Piscitelli
Edited by
Steven L. Zeichner  and
Jennifer S. Read
Stephen C. Piscitelli
Affiliation:
Discovery Medicine – Antivirals, GlaxoSmithKline, Research Triangle Park, NC
Steven L. Zeichner
Affiliation:
National Cancer Institute, Bethesda, Maryland
Jennifer S. Read
Affiliation:
National Institutes of Health, Bethesda, Maryland
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Summary

Therapeutic drug monitoring (TDM) refers to the adjustment of drug doses based on measured plasma concentrations to attain values within a “therapeutic window.” Clinicians have used these principles for years to adjust doses of many drugs, however, TDM has not generally been used for monitoring the treatment of chronic infectious diseases. There is growing evidence that TDM may be useful in some circumstances to ensure HIV-infected patients have adequate blood concentrations for efficacy without producing toxicity. This may be especially true for children where there is wide variability in plasma concentrations. A number of critical questions remain to be addressed before TDM is used routinely in HIV infection.

Retrospective studies have demonstrated plasma concentrations of antiretroviral drugs correlate with antiviral activity [1–4]. It is clear that drug concentrations are an important predictor of response to HIV treatment. However, these findings are quite different than assessing the value of using TDM in the clinic to guide antiretroviral therapy for an individual.

Drugs as TDM candidates

Some antiretrovirals share many of the characteristics of drugs that require monitoring of plasma levels, including variable inter-subject pharmacokinetics, serious consequences if there is a lack of effect or drug toxicity, documented relationships between drug concentration and effect or toxicity, identification of a therapeutic range, and the availability of rapid and accurate assays.

Plasma concentrations of protease inhibitors (PIs) may vary by more than ten-fold between individuals receiving the same dose [5].

Type
Chapter
Information
Handbook of Pediatric HIV Care , pp. 439 - 449
Publisher: Cambridge University Press
Print publication year: 2006

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References

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