Mycophenolic acid monitoring in HTX patients: a preliminary report.

Mycophenolic acid (MPA) is a new immunosuppressive drug used in clinical trials in combination with cyclosporine A (CsA) and prednisolone. Its immunosuppressive mechanism consists in a non-competitive inhibition of the inosine monophosphate (IMP) dehydrogenase which is the key enzyme in the conversion of inosine monophosphate to guanosine monophosphate. Depletion of the guanine nucleotide pool impairs DNA synthesis and thus inhibits the cell cycle progression of T- and B-lymphocytes. For monitoring of MPA and its metabolite mycophenolic acid glucuronide (MPAG), a high performance liquid chromatography (HPLC) method, and for MPA an EMIT-immunoassay, were established. MPA HPLC and EMIT exhibit a linearity up to 10.00 mumol/l (3.20 micrograms/ml) and 46.95 mumol/l (15.00 micrograms/ml) respectively. Coefficients of variation for intra /inter-assay bias were 5.3/14.1 per cent for HPLC and 4.8/12.3 percent for the EMIT assay. The correlation between both methods was: HPLC = 0.82 EMIT -1.85 (r = 0.955); limits of agreement between the methods were 13.6 and -5.12 mumol/l. In 8 stable heart transplant recipients treated with 2 g mofetil/day, mean and median steady-state MPA concentrations for HPLC and EMIT were 6.86 mumol/l (2.19 micrograms/ml), 4.77 mumol/l (1.52 micrograms/ml) and 10.88 mumol/l (3.48 micrograms/ml), 7.42 mumol/l (2.37 micrograms/ml) respectively, during a period of 3 months. Mean and median MPAG concentrations were 141.21 mumol/l (61.40 micrograms/ml) and 100.70 mumol/l (43.78 micrograms/ml) respectively.