Abstract
The pharmacokinetics of mycophenolic acid (MPA) and its glucuronide (mycophenolic acid phenolic glucuronide, MPAG) in lupus nephritis (LN) have not been fully characterized. The aim of this study was to evaluate the pharmacokinetics of MPA and MPAG in LN patients by comparing the pharmacokinetics with those of kidney transplant (KT) recipients. Six LN patients (World Health Organization class IV and V) and 24 KT recipients [8 recipients treated with tacrolimus (Tac) and 16 with cyclosporine (CyA)] during the early posttransplantation period were enrolled. Pharmacokinetic parameters of MPA and MPAG were compared between LN patients and Tac-treated or CyA-treated KT recipients. The area under the concentration-time curve (AUC0-12) of MPA normalized to mycophenolate mofetil (MMF) dose (mg/kg) was significantly lower in LN patients and CyA-treated KT recipients than in Tac-treated KT recipients [median (range), 2.19 (0.87-4.23), 2.36 (1.13-5.74), and 4.86 (3.25-6.75) microg x h/mL per mg/kg, P < 0.05 and P < 0.01, respectively]. Dose-normalized MPAG AUC0-12 was significantly lower in LN patients and slightly lower in Tac-treated KT recipients than in CyA-treated KT recipients [median (range), 35.0 (8.34-69.8), 51.6 (34.4-94.8), and 84.1 (34.7-152) microg x h/mL per mg/kg, P < 0.05 and P = 0.13, respectively]. The ratio of MPA AUC5-12 to AUC0-12, an estimate of MPA enterohepatic recirculation, was slightly higher in LN patients and Tac-treated KT recipients than in CyA-treated KT recipients [median (range), 0.44 (0.35-0.56), 0.45 (0.42-0.61), and 0.34 (0.22-0.55), P = 0.29 and P = 0.10, respectively]. Serum creatinine was significantly lower in LN patients than in Tac-treated and CyA-treated KT recipients. In conclusion, the pharmacokinetics of MPA in LN patients is characterized by high MPA clearance and in CyA-treated KT recipients. Despite this higher clearance of MPA, MPAG AUC0-12 was lower in LN patients most likely due to better renal function in LN patients.
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