Effect of mycophenolate mofetil on IMP dehydrogenase after the first dose and after long-term treatment in renal transplant recipients

P Glander, P Hambach, K P Braun, L Fritsche, J Waiser, I Mai, H H Neumayer, K Budde
International Journal of Clinical Pharmacology and Therapeutics 2003, 41 (10): 470-6

OBJECTIVE: Mycophenolate mofetil (MMF) is routinely used as an immunosuppressant in a fixed daily dose regimen although it shows marked fluctuations in pharmacokinetics, and despite the fact that in regard to the active metabolite, mycophenolic acid (MPA), there is a well-known association between the pharmacokinetic parameters and clinical outcome.

METHOD: In order to determine the time course and the variability in cellular target of MPA after renal transplantation, we investigated the pharmacodynamic response in 8 patients receiving 1 g MMF for the first time prior to renal transplantation and in 8 stable renal transplant patients maintained on long-term MMF therapy (1 g b.i.d.) for more than 1 year. The pharmacodynamic response was measured using inosine 5'-monophosphate dehydrogenase (IMPDH) activity in peripheral mononuclear cells. MPA plasma concentrations were measured in parallel, IMPDH activity in 89 healthy blood donors was used as a control.

RESULTS: We observed a high interindividual variability in IMPDH activity in the 89 untreated healthy volunteers (4.0 - 32.9 nmol/h/mg protein), in 8 patients on dialysis (5.3 - 18.9 nmol/h/mg protein) and in 8 renal transplant patients under long-term MMF treatment (2.3 - 14.4 nmol/h/mg protein). The mean AUC0-12h for mycophenolic acid was 2-fold higher in patients receiving long-term treatment with MMF (62.2 +/- 16.6 mg x h/ml) compared to dialysis patients receiving 1 g MMF for the first time (31.5 +/- 15.6 mg x h/ml). Despite this pharmacokinetic difference there were no statistically significant differences in the cellular pharmacodynamic response. Minimal IMPDH activity (1.62 +/- 1.23 vs. 1.77 +/- 1.49 nmol/h/mg protein) and maximal IMPDH inhibition (87.5 +/- 0.08 vs. 77.4 +/- 18.8%) during the dosing interval were similar.

CONCLUSIONS: The considerable interindividual variability in the pharmacokinetics of MMF as well as in the drug target support the use of pharmacodynamic drug monitoring to optimize MMF dosing and to reduce the risk of graft rejection and side effects.

Full Text Links

Find Full Text Links for this Article


You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read

Save your favorite articles in one place with a free QxMD account.


Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"