Abstract
The pharmacokinetics of mycophenolic acid (MPA) was studied in 23 kidney transplant recipients with stable, long-term graft function who were receiving mycophenolate mofetil (MMF) in combination with either tacrolimus or sirolimus therapy. After 500 mg MMF, the mean MPA area under the curve (AUC) was significantly lower in sirolimus-treated patients than in those treated with tacrolimus (35.4 +/- 32.3 vs. 77.1 +/- 67.5 mg/l). MPA peak plasma concentration (C(max)) and MPA trough plasma concentration (C(min)) were significantly higher in patients who received tacrolimus than in those who received sirolimus. There were no significant differences between the two groups with respect to MPA time to maximum concentration (T(max)), MPA-glucuronide (MPAG) AUC, MPAG C(max), MPAG C(min), MPAG T(max), MPA-acyl-glucuronide (AcMPAG) AUC, AcMPAG C(max), AcMPAG C(min), and AcMPAG T(max). In conclusion, MPA exposure is greater in tacrolimus-treated patients than in those treated with sirolimus during maintenance immunosuppression after kidney transplant. It is suggested that the influence of tacrolimus on the pharmacokinetics of MPA reflects an interaction of the two agents at the level of their intestinal absorption.
Published Version
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