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45 - The use of biomarkers for monitoring the response to immunosuppressive drug therapy

Published online by Cambridge University Press:  20 August 2009

Atholl Johnston
Affiliation:
St Bartholomew's and the Royal London School of Medicine and Dentistry, London, UK
Andrew K. Trull
Affiliation:
Papworth Hospital, Cambridge
Lawrence M. Demers
Affiliation:
Pennsylvania State University
David W. Holt
Affiliation:
St George's Hospital Medical School, University of London
Atholl Johnston
Affiliation:
St. Bartholomew's Hospital and the Royal London School of Medicine and Dentistry
J. Michael Tredger
Affiliation:
Guy's, King's and St Thomas' School of Medicine
Christopher P. Price
Affiliation:
St Bartholomew's Hospital and Royal London School of Medicine & Dentistry
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Summary

Introduction

Immunosuppressive drug therapy is used to prevent acute or chronic rejection of organ allografts in patients who have received a transplant. As with most prophylactic treatments, it only becomes apparent that the treatment has failed when the unwanted event happens. If there is a large safety margin between the dose of drug that prevents the unwanted event and the dose at which unacceptable drug toxicity occurs then the drug dose given can be sufficiently high to ensure treatment effectiveness. However, in transplant patients, the consequences of under- or over-immunosuppression can be equally catastrophic. On the one hand, underimmunosuppression can result in organ rejection that may, in turn, lead to graft loss and even death, while, on the other hand, overimmunosuppression can result in life-threatening infections, carcinoma and a range of drug-related adverse events such as nephrotoxicity. At present, we use plasma or blood drug concentrations as a surrogate measure of immunosuppression in the belief that there is a tight relationship between drug concentration and effect [1]. However, interindividual variation in pharmacological response can make drug concentration data difficult to interpret. For this reason, the use of biomarkers for monitoring the response to immunosuppressive drug therapy has been investigated.

Choice of biomarker

The choice of biomarkers for monitoring the response to immunosuppressive drug therapy is wide. Monitoring the effect of therapy on the primary intracellular drug targets offers the most promise, but these targets are also the most difficult to measure (Table 45.1).

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Information
Biomarkers of Disease
An Evidence-Based Approach
, pp. 451 - 460
Publisher: Cambridge University Press
Print publication year: 2002

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