A pilot study on area under curve of mycophenolic acid as a guide for its optimal use in renal transplant recipients.

Background & objectives: The immunosuppressants administered to renal transplant subjects are usually monitored therapeutically to prevent graft rejection and drug toxicity. Mycophenolic acid (MPA) is an immunosuppressant. The present prospective study was undertaken to establish the utility of plasma level monitoring of MPA and to correlate it with clinical outcomes in renal transplant receipients. Methods: MPA plasma level at 2, 4 and 9 h and the area under concentration-time curve (AUC) were estimated using high performance liquid chromatography in 24 renal transplant recipients receiving immunosuppressant MPA plus tacrolimus and steroid. Results: There was wide inter-individual variation in MPA plasma level and the AUC. The incidences of gastrointestinal adverse drug events (diarrhoea and acidity) were significantly more in the high MPA AUC patients. Though biopsy proven acute rejection was not found, of the six subjects with lower MPA AUC (<30 mg.h/l), three were clinically diagnosed to develop tacrolimus nephrotoxicity. The Gastrointestinal Symptom Rating Scale (GSRS) and Gastrointestinal Quality of Life Index (GIQLI) scores represented better health related quality of life in lower MPA AUC than in the higher MPA AUC (>60 mg.h/l). Interpretation & conclusions: The present findings suggest the MPA AUC of 30 - 60 mg.h/l in the maintenance stage of renal transplant patients to have optimum clinical benefit and relegated adverse events profile indicating the usefulness of AUC of MPA with limited sampling strategy in optimizing its use.

A six-hour extrapolated sampling strategy for monitoring mycophenolic acid in renal transplant patients in the Indian subcontinent.

BACKGROUND: Therapeutic drug monitoring for mycophenolic acid (MPA) is increasingly being advocated. The present therapeutic range relates to the 12-hour area under the serum concentration time profile (AUC).However, this is a cumbersome, tedious, cost restricting procedure. Is it possible to reduce this sampling period? AIM: To compare the AUC from a reduced sampling strategy with the full 12-hour profile for MPA. SETTINGS AND DESIGN: Clinical Pharmacology Unit of a tertiary care hospital in South India. Retrospective, paired data. MATERIALS AND METHODS: Thirty-four 12-hour profiles from post-renal transplant patients on Cellcept were evaluated. Profiles were grouped according to steroid and immunosuppressant co-medication and the time after transplant. MPA was estimated by high performance liquid chromatography with UV detection. From the 12-hour profiles the AUC up to only six hours was calculated by the trapezoidal rule and a correction factor applied. These two AUCs were then compared. STATISTICAL ANALYSIS: Linear regression, intra-class correlations (ICC) and a two-tailed paired t-test were applied to the data. RESULTS: Comparing the 12-hour AUC with the paired 6-hour extrapolated AUC, the ICC and linear regression(r2) were very good for all three groups. No statistical difference was found by a two-tailed paired t-test. No bias was seen with a Bland Altman plot or by calculation. CONCLUSION: For patients on Cellcept with prednisolone +/- cyclosporine the 6-hour corrected is an accurate measure of the full 12-hour AUC.