THE MYCOPHENOLATE THERAPEUTIC DRUG MONITORING BY AREA UNDER THE CURVE IS AFFECTED BY SERUM CREATININE AND TIME!

Introduction:

Introduction: Underexposure and overexposure to immunosuppression leads to increased rejection and infection respectively. Measuring Mycophenolate drug levels is currently not standard of care. Hence the factors affecting the Mycophenolate drug levels are not understood by the transplant fraternity. This study attempts to make the transplant fraternity aware of some of the clinically significant factors to help them make decisions even if therapeutic drug monitoring for Mycophenolate is not their transplant unit protocol.

Methods:

Aims & Objectives: To determine if serum creatinine and time after kidney transplant affect the Mycophenolate Area Under the curve (MPA AUC).

Methods: Single arm, observation study of post kidney transplant patients. The MPA trough is measured 12 hr after last dose of Mycophenolate mofetil and AUC constructed by 8 sample strategy.1 The total plasma level of mycophenolic acid was measured by HPLC. Patients received triple immunosuppression with oral prednisolone, Tacrolimus and Mycophenolate mofetil. Descriptive analysis for demographic data, transformation of data for stabilizing inter-patient variation by Boxcox to fix threshold limits for MPA-AUC, ANOVA for significance between levels of immunosuppressive agents, generalized linear regression and mixed factor analysis to find mean levels of immunosuppressive agents with concomitant drugs with contour plot, factorial plot and control charts were carried out.

Results:

Results: 52 patients (7 females + 45 males) were observed since 2016 to 2024. All were alive with zero graft loss or patient loss. The mean MPA AUC was 36.7±16.8 mg.hr/L (15.3 – 85.4). The mean serum creatinine before the MPA AUC testing was 1.26±0.52 mg/dl (0.75-4.43). The immediate tacrolimus trough at the time of MPA AUC was 11.2±5.7 ng/ml. There was 13 units increase in MPA AUC for every 1 mg/dl increase in creatinine (p=0.004) (Figure 1) . There was no correlation between Tacrolimus trough and MPA AUC. The MPA AUC variation is high (Figure 2) between 18.35 – 70.42 mg.hr/L (95%CI). The MPA AUC increased with time especially after 1 year with mean MPA AUC increasing 50%  for same dose of Mycophenolate. Hence to optimise the level to a mean of 40 mg.hr/L or a range of 30-60 mg.hr/L it needed the MPA AUC is done and dose modified at least 2 times in 6 months and once after 1 year.

Conclusions:

Conclusion: MPA AUC increases by 13 units for every 1 mg/dl increase in serum creatinine. The dose of MPA AUC needs to be adjusted for increase in serum creatinine to avoid mycophenolate toxicity whenever there is acute or chronic graft dysfunction. MPA AUC increases by 50% after 1 year compared to a value in the first 3 months post kidney transplantation.

I have no potential conflict of interest to disclose.

I did not use generative AI and AI-assisted technologies in the writing process.