The influence of calcineurin inhibitors on mycophenolic acid pharmacokinetics.
Despite the fact that concentrations of mycophenolic acid (MPA) are not routinely measured, accumulating data suggest the usefulness of this monitoring to optimize therapy. The aim of this study was to assess the influence of CsA and tacrolimus on MPA pharmacokinetics. Concentrations of MPA were measured using HPLC. An assay was performed before dose (the C(0)), as well as at 40 minutes and 1, 2, 4, 6, 8, 10, 12 hours after administration of mycophenolate mofetil (MMF). MPA profiles were assessed in 51 patients receiving tacrolimus at a dose of 1.0 g/d and prednisone as well as in 97 patients receiving CsA (2.0 g/d) and prednisone. Significant correlations of MPA levels with serum albumin and GFR were observed in both groups. Women presented with higher levels of MPA than men. C(0) MPA level among the tacrolimus group were significantly higher than those in CsA group: 3.18 +/- 2.21 microg/mL versus 1.68 +/- 1.03 microg/mL (P </=.001). The level of MPA AUC((0-12)) in the tacrolimus group was nonsignificantly higher than that in the CsA group. There was no second peak of MPA level in a group of patients receiving CsA. We developed a limited sampling strategy to estimate MPA AUC((0-12)) in both tacrolimus and CsA groups. We observed a correlation between C(0) MPA and C(0) CsA (r =.35; P </=.001) as well as, between tacrolimus dose and MPA C(40) and MPA C(max) (r =.24; P </=.05; r =.27; P </= 0.05, respectively). No relationship between MPA pharmacokinetics and tacrolimus blood concentrations was noticed. Tacrolimus and CsA both affect the pharmacokinetics of MPA; high MPA concentrations in patients treated with tacrolimus justify MMF dose reduction in this group. Alterations of CsA concentrations must be used to guide MMF dose adjustments.
Kuriata-Kordek
M
M
Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Wroclaw, Poland.
Boratynska
M
M
Falkiewicz
K
K
Porazko
T
T
Urbaniak
J
J
Wozniak
M
M
Patrzalek
D
D
Szyber
P
P
Klinger
M
M
D000328:Adult; D065095:Calcineurin Inhibitors; D016572:Cyclosporine / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D005919:Glomerular Filtration Rate / Q000502:physiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008657:Metabolic Clearance Rate; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011241:Prednisone / Q000627:therapeutic use; D012189:Retrospective Studies; D012709:Serum Albumin / Q000378:metabolism; D016559:Tacrolimus / Q000627:therapeutic use; D013997:Time Factors
D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D012709:Serum Albumin; D016572:Cyclosporine; D009173:Mycophenolic Acid; D011241:Prednisone; D016559:Tacrolimus