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Optimizing Mycophenolic Acid Exposure in Kidney Transplant Recipients: Time for Target Concentration Intervention.
David K Metz1,2,3,4, Nick Holford5, Joshua Y Kausman1,2,3
1Department of Nephrology, Royal Children's Hospital, Melbourne, VIC, Australia.
Transplantation
|October 5, 2019
Summary
Fixed mycophenolate dosing in kidney transplants leads to poor outcomes. Concentration-controlled dosing (CCD) optimizes exposure, improving efficacy and reducing toxicity, making it a superior strategy.
Area of Science:
- Immunology
- Pharmacology
- Nephrology
Background:
- Mycophenolate is a key immunosuppressant in kidney transplantation.
- Current dosing strategies vary, including fixed dosing and concentration monitoring.
- Inconsistent trial results have hindered widespread adoption of concentration-controlled dosing (CCD).
Purpose of the Study:
- To review evidence supporting mycophenolate CCD in kidney transplantation.
- To evaluate the impact of different dosing strategies on efficacy and toxicity.
- To provide recommendations for optimizing mycophenolate therapy.
Main Methods:
- Comprehensive review of pharmacological data.
- Analysis of observational studies linking mycophenolic acid (MPA) exposure to outcomes.
- Examination of randomized controlled trials of CCD.
Main Results:
- Fixed dosing is associated with both under- and overexposure, leading to rejection and toxicity.
- Pharmacokinetic-guided CCD successfully controls MPA exposure and improves clinical outcomes.
- Target concentration intervention demonstrates clear clinical benefits.
Conclusions:
- Fixed mycophenolate dosing is suboptimal for kidney transplant recipients.
- Clinically proven MPA target concentration strategies should replace fixed dosing.
- Further research is needed to define optimal maintenance phase targets for CCD.
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