Pharmacokinetics of mycophenolate sodium co-administered with tacrolimus in the first year after renal transplantation
2016
We assessed the relations between MPA, free MPA (fMPA) and MPA glucuronide (MPAG) pharmacokinetics and the clinical condition of renal transplant recipients treated with EC-MPS and tacrolimus (Tac) in the first post-transplant year. In 18 adult patients blood samples were collected up to 12 h after EC-MPS oral administration. EC-MPS metabolites’ plasma concentrations were determined using validated HPLC methods. All patients reached MPA area under the time–concentration curve (AUC0–12) above 30 µg h/mL. Most of the MPA, fMPA and all MPAG concentrations correlated significantly with respective AUC0–12 values. Some fMPA and all MPAG pharmacokinetic parameters correlated negatively with creatinine clearance and positively with creatinine concentration, whereas no such correlation was observed for MPA. Lower hemoglobin concentrations were observed in patients with higher MPA or fMPA C 0. The significant correlations between MPA C 3 as well as MPA C 4 and MPA AUC0–4 and MPA AUC0–12 may be of importance in further studies including larger number of patients in regard to establishing LSS. In patients treated with EC-MPS and Tac, monitoring MPA C 0 may be important, as too high MPA C 0 may contribute to anemia onset. In EC-MPS treated patients, MPAG concentration is related to renal function as MPAG pharmacokinetics were higher in patients with renal impairment.
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