Pharmacokinetics of mycophenolic acid and its phenyl glucuronide metabolite in kidney transplant recipients with renal impairment Table II. Dose-corrected PK parameters* of MPA and MPAG classified by renal function PK – pharmacokinetic, MPA – mycophenolic acid, MPAG – 7-O-mycophenolic acid glucuronide, CV – coefficient of variation, Ccr – creatinine clear- ance, AUC – area under the concentration-time curve, C0 – pre-dose concentration, Cmax – maximum concentration, *the results are presented as median (range), **comparison between patients with Ccr > 60 ml/min and < 60 ml/min, Mann-Whitney test Table III. Dose-corrected PK parameters* of MPA and MPAG in patients treated with Tac or CsA classified by renal function Tac (n = 22) Value of p* CsA (n = 21) Value of p** CV (%) Ccr > 60 ml/min (n = 17) CV (%) Ccr < 60 ml/min (n = 26) CV (%) Value of p** 31.0 60.4 40.9 57.0 72.9 58.2 19.01 (14.45-30.48) 1.48 (0.44-2.39) 10.35 (5.50-24.13) 172.47 (112.67-306.15) 29.65 (8.26-53.63) 50.94 (33.95-87.49) 23.4 43.3 42.0 29.3 41.8 27.6 21.25 (8.71-35.46) 2.24 (0.50-5.26) 10.07 (3.74-18.92) 299.94 (170.11-857.26) 61.01 (29.63-185.90) 103.92 (44.81-240.30) 34.7 55.6 39.9 47.8 60.8 47.6 Parameter MPA AUC0-4 h [μg × h/ml] C0 [μg/ml] Cmax [μg/ml] MPAG AUC0-4 h [μg × h/ml] C0 [μg/ml] Cmax [μg/ml] MPA AUC0-4 h [μg × h/ml] C0 [μg/ml] Cmax [μg/ml] MPAG AUC0-4 h [μg × h/ml] C0 [μg/ml] Cmax [μg/ml] All (n = 43) 19.40 (8.71-35.46) 1.93 (0.44-5.26) 10.35 (3.74-24.13) 235.68 (112.67-857.26) 36.44 (8.26-185.90) 68.21 (33.95-240.30) Ccr > 60 ml/min (n = 9) Ccr < 60 ml/min (n = 13) Ccr > 60 ml/min (n = 8) Ccr < 60 ml/min (n = 13) 19.96 (14.83-30.48) 1.98 (0.73-2.30) 13.96 (5.50-24.13) 189.06 (112.67-229.25) 31.06 (10.70-42.47) 50.94 (33.95-68.21) 21.91 (11.83-35.46) 2.46 (0.76-5.26) 9.20 (5.63-18.92) 298.05 (170.11-588.54) 39.07 (29.63-133.84) 100.43 (44.81-226.41) 0.537 0.037 0.643 0.014 0.014 0.021 16.51 (14.45-23.71) 1.11 (0.44-2.39) 8.90 (6.20-18.08) 168.36 (124.12-306.15) 25.66 (8.26-53.63) 52.13 (39.77-87.49) 20.58 (8.71-32.47) 1.90 (0.50-4.37) 10.49 (3.74-17.17) 359.29 (195.42-857.26) 66.80 (33.99-185.90) 115.50 (61.67-240.30) PK – pharmacokinetic, MPA – mycophenolic acid, MPAG – 7-O-mycophenolic acid glucuronide, Tac – tacrolimus, CsA – cyclosporine, Ccr – creati- nine clearance, AUC – area under the concentration-time curve, C0 – pre-dose concentration, Cmax – maximum concentration, *the results are presented as median (range), **comparison between patients with Ccr > 60 ml/min and < 60 ml/min, Mann-Whitney test renal function exceeded 30% for all PK parameters evaluated. The CV values were lower for MPA AUC0-4 h compared to MPA C0 (Table II). Discussion In our study we analysed the influence of renal function on MPA and MPAG PK in patients during the maintenance period following renal transplan- tation. The concentrations of both MMF metabo- lites (MPA and MPAG) varied widely, particularly in patients with impaired renal function, despite MMF dose correction. Similar variability was also pre- sented by other authors [11-13]. Total drug exposure is best demonstrated by AUC0-12 h. In clinical practice this parameter is diffi- cult to assess, especially in patients treated in clin- ics during the maintenance period following renal transplantation. In our study, blood samples were collected within 4 h after drug administration due to the short duration of the patient’s stay in hos- pital during a routine appointment in a transplant Arch Med Sci 1, February / 2012 91 0.285 0.010 0.650 < 0.001 < 0.001 < 0.001 0.311 0.060 0.717 0.002 0.003 0.002