Mycophenolic acid trough levels after kidney transplantation in a cyclosporine-free protocol.
Twenty-seven stable kidney transplant recipients treated with cyclosporine and prednisone were converted to mycophenolate mofetil (MMF) and prednisone 1 year after transplantation. After conversion the patients were treated with a standard daily dose of 1 g MMF b.i.d. and 10 mg prednisone for 4 months. Thereafter, two MMF dose reductions were performed with a 4-month interval. Mycophenolic acid (MPA) trough levels were measured at regular intervals. A relation was found between MPA trough levels and MMF dose. The median MPA trough level for patients treated with 1 g MMF b.i.d. was 4.3 microg/ml (0.95-15.5) and 3.0 microg/ml (0.73-7.8) for patients treated with 750 mg b.i.d. (P = 0.0002). The MPA trough levels further decreased from 3.0 to 2.3 microg/ml (0.6-6.63) in patients treated with 500 mg MMF b.i.d. (P = 0.01). Dose reduction of MMF from 1 g to 750 mg b.i.d. could be performed without acute rejections. A further dose reduction to 500 mg b.i.d. elicited 3 rejections. Patients experiencing an acute rejection had a median MPA trough level of 2.3 microg/ml (1.26-3.38) compared to 3.8 microg/ml (1.48-6.52) in patients without an acute rejection (P = 0.25). We conclude that there is a significant relation between MPA trough levels and MMF dose. MPA trough levels were not predictive of rejection in the present study.
Smak Gregoor
P J
PJ
Department of Internal Medicine I, University Hospital Rotterdam, The Netherlands. SMAKGREGOOR@INW1.AZR.NL
van Gelder
T
T
van Besouw
N M
NM
van der Mast
B J
BJ
Hesse
C J
CJ
IJzermans
J N
JN
Weimar
W
W
D019540:Area Under Curve; D016572:Cyclosporine / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000276:immunology*; D009173:Mycophenolic Acid / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D011241:Prednisone / Q000627:therapeutic use; D011446:Prospective Studies; D013997:Time Factors
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid; D011241:Prednisone