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. Thepresent 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 samplingperiod?
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, paireddata.
Materials and Methods : Thirty-four 12-hour profiles from post-renal transplant patients on Cellcept ® wereevaluated. Profiles were grouped according to steroid and immunosuppressant co-medication and the timeafter transplant. MPA was estimated by high performance liquid chromatography with UV detection. From the12-hour profiles the AUC up to only six hours was calculated by the trapezoidal rule and a correction factorapplied. These two AUCs were then compared.
Statistical Analysis : Linear regression, intra-class correlations (ICC) and a two-tailed paired t-test were appliedto 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. Nobias was seen with a Bland Altman plot or by calculation.
Conclusion : For patients on Cellcept ® with prednisolone ± cyclosporine the 6-hour corrected is an accuratemeasure of the full 12-hour AUC.