Individualizing Immunosuppressive Therapy for Transplant Patients

Therapeutic drug monitoring (TDM),2 the quantitative determination of compounds administered with therapeutic intent, is one way personalized medicine is practiced. Traditionally, medications are measured in the appropriate matrix (serum, plasma, or whole blood) and are used to individualize the dosage regimen with the intent to maximize efficacy and minimize toxicity. There are numerous classes of medications (e.g., antiarrhythmics, antibiotics, antiepileptics, psychiatric drugs) for which TDM is routinely used. Immunosuppressive drugs (e.g., tacrolimus, cyclosporine) given after transplant represent another class of drugs that have narrow therapeutic ranges and significant inter- and intraindividual variability in dosing requirements. Tacrolimus, a mainstay immunosuppressant drug used in solid-organ transplants, is one example of a drug for which TDM is important. Underdosing of tacrolimus may result in inadequate immunosuppression and acute rejection, while overdosing puts patients at risk for considerable neuro- and nephrotoxicity. For decades, the standard of care has been for clinicians to adjust the dose of an immunosuppressant drug in response to a whole blood trough concentration and established target therapeutic ranges. These decisions are made largely on the basis of clinical experience, and patients frequently deviate from the target range, running the alternate risks of toxicity and graft rejection. With the use of this strategy, a 78% 5-year survival rate for liver transplant recipients has been achieved [http://www.mayoclinic.org/tests-procedures/liver-transplant/basics/results/prc-20014076 (accessed July 2016)], but these success rates indicate there is still room for improvement.