The influence of calcineurin inhibitors on mycophenolic acid pharmacokinetics
ABSTRACT 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.
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ABSTRACT: To observe the different concentrations of mycophenolic acid (MPA) during the early post-transplant phase for various combinations of cyclosporine A (CsA) and tacrolimus (Tac) with enteric-coated mycophenolate sodium (EC-MPS). A total of 42 Chinese adults receiving live related donor kidney transplants were studied. All received a triple immunosuppressive regimen of EC-MPS, CsA/Tac and corticosteroids and were divided randomly into CsA (n = 21) and Tac (n = 21) combination groups. The dosage of EC-MPS was the same (1440 mg/day) in the two groups. The MPA concentration was evaluated with an enzyme-multiplied immunoassay technique (EMIT) and the pharmacokinetic characteristics were investigated in both groups. The mean maximum plasma concentrations (Cmax ) of MPA in the CsA and Tac groups were 11.365 ± 9.522 and 9.748 ± 7.523 μg/ml, respectively (p = 0.137). The maximum times to Cmax (Tmax ) were 2.54 ± 1.53 and 2.67 ± 1.08 h, respectively (p = 0.341). The mean MPA 12-h areas under the curve (MPA-AUC0-12 h ) were 59.463 ± 16.252 and 77.535 ± 33.615 μg h/ml (p = 0.003) and the mean residence times (MRT) were 3.71 ± 0.829 and 3.928 ± 0.923 h (p = 0.038). Combined with the same EC-MPS dosage (1440 mg/day), the MPA-AUC0-12 of the Tac group was higher than that of the CsA group, and the Tac group had a longer MRT after kidney transplantation. Our data indicate that the concentration of MPA should be monitored in clinical therapy when EC-MPS is combined with different calcineurin inhibitors to reduce acute allograft rejection and avoid adverse events.International journal of clinical practice. Supplement 04/2014; 68(181):4-9. DOI:10.1111/ijcp.12400
Liver Transplantation 07/2006; 12(7). DOI:10.1002/lt.20842 · 3.79 Impact Factor