Relationship between mycophenolate mofetil side effects and mycophenolic acid plasma trough levels in renal transplant patients

There has been limited experience with routine therapeutic monitoring of my cophenolic acid (MPA: CAS 24280-93-1). which is the active metabolite of th e new immunosuppressive prodrug mycophenolate mofetil (MMF, CAS 115007-34-6 ). MMF was introduced with recommendation for fixed oral dosing (1 g twice daily) in combination with cyclosporin A (CSA) and a glucocorticoid for the prevention of renal allograft rejection. In the course of routine CSA moni toring a MPA monitoring was performed in adult renal transplant patients re ceiving MMF in combination with CSA and methylprednisolone (MEP). For 30 co nsecutive patients with 234 plasma samples the relationship of MMF doses us ed and MPA plasma through levels estimated at steady state (C-ss min) to cl inical outcome was evaluated retrospectively. The MPA concentrations were d etermined with the enzyme-multiplied immunoassay technique (EMIT(R) mycophe nolic acid assay) on a Cobas Mira Plus analyzer. The within-run (n = 10) an d between-run (n = 10) coefficients of variation were 3.6 %, 3.5 %, 3.1 % a nd 3.6 %, 5.1 %, 6.7 % analysing three MPA level plasma controls (1.25 mg/l , 7.5 mg/l, 12.5 mg/l), respectively. The data analysis of the MPA plasma t rough levels resulted in a high variability between patients (0.3 to 3.4 mg /l) received the recommended fixed MMF dose (2 g/day). There was a higher i ncidence of adverse reactions with increasing MPA plasma trough levels (2.1 3 +/- 1.35 mg/l in 13 patients with side effects versus 1.53 +/- 0.67 mdl i n 17 patients without side effects: p < 0.001). regardless of reduction of MMF dose (1.77 +/- 0.3 g/day versus 1.89 +/- 0.2 g/day NS, respectively. No acute rejection episodes occured under MMF administration in combination w ith CSA and MEP. The study shows that the to date recommended MMF dose resu lted in individual, quite different MPA plasma trough levels, which were as sociated with incidence of side effects rather than the MMF doses. Therefor e, monitoring of plasma MPA trough levels and individual dose adjustment co uld be helpful to reduce the incidence of adverse reactions and to increase the safety of MMF therapy.