Pharmacokinetics of mycophenolic acid in renal transplant patients after first-dosing and in steady-state

Objective To investigate the pharmacokinetic profiles of mycophenolic acid (MPA), an active metabolite of the prodrug mycophenolate mofetil(MMF) after first oral dosing (MMF 1g) and in steady-state, thereby assessing the accumulation of MPA in renal transplant patients. Methods Eight adult kidney recipients(male 3, female 5) were included in the study. MPA pharmacokinetic profiles were obtained after first oral dosing( MMF 1g) and in steady-state (MMF 1g, q12h, 7days), plasma MPA concentrations were determined by HPLC method. The concentration-time curves of MPA were fitted to a two-compartment model. The pharmacokinetic parameters were calculated by 3P87 pharmacokinetic software. Results The main pharmacokinetic parameters after first-dose and steady-state were as follows: f1/2β were,2.78 ±7.29 and 12.30 ±5.57 h(P0.05); Cmaxwere 14.29 +±6.85 and 19.72±5.83 mg-L-1 (P0.01), AUC0-12h were 44.57 ± 9.61 and 64.26 ± 16.59 mg·h·L-1(P0.01); CL(s) were 15.51 ±2.53 and 11.16 ±3.53 L-h-1 (P0.01); the ratio of Cmax and AUC0-12h of steady-state administration to the first dose administration were 1.54 ± 0.56 and 1.48 ± 0.36, respectively. Conclusion The accumulation for MPA after repetitive MMF administration in renal ransplant patients was detected. Plasma MPA concentration should be monitored routinely in clinical practice.