What is it about?
MMF therapy was introduced in the 90ies as a replacement therapy for azathioprine with concomitant cyclosporine for immunosuppression. There are substantial drug drug interactions between both drugs, and the active compound of MMF, mycophenolic acid (MPA) exposure could only be assessed with a pharmacokinetic profile. Even with limited sampling strategies, this is not feasible for the follow-up of renal transplant recipients. The utility of the trough level for concomitant tacrolimus has been understudied, and we found it to be quite useful as a surrogate for the MPA exposure. The intrapatient variability, however, was greater than that of tacrolimus. Regardless, MPA trough level monitoring may help to improve the safety and efficacy of MMF therapy with concomitant tacrolimus therapy.
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Why is it important?
There is evidence for increased rejection if MPA exposure (measured as 12-hour AUC) is below 30 mg x h/L, and measuring MPA trough levels can help to avoid MPA underexposure. Maintaining an MPA trough level > 1.3 mg/L may also help to reduce donor-specific antibody formation. Overexposure also needs to be avoided, but the upper therapeutic window has not been well defined.
Perspectives
To date, there is no effective strategy to prevent donor specific antibody (DSA) formation. DSA formation is associated with poorer graft survival and makes retransplantation more difficult. There is some preliminary evidence that MPA monitoring and maintaining a trough level > 1.3 mg/L may serve as a strategy to reduce DSA formation. The intrapatient variability is also a tool for measuring compliance or adherence, which is a major problem in adolescent renal transplant recipients.
Professor Guido Filler
Western University
Read the Original
This page is a summary of: What is the intrapatient variability of mycophenolic acid trough levels?, Pediatric Transplantation, July 2015, Wiley,
DOI: 10.1111/petr.12559.
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