Influence of renal graft function on mycophenolic acid pharmacokinetics during the early period after kidney transplant.
OBJECTIVE
Mycophenolate mofetil, the prodrug of mycophenolic acid, is widely used for maintenance immunosuppressive therapy in renal transplant recipients. The effect of renal graft function on mycophenolic acid pharmacokinetics parameters is still controversial. The aim of this study is to investigate the impact of renal graft function on mycophenolic acid pharmacokinetics during the early posttransplant period.


METHODS
Our study was done on 13 patients with severe renal impairment (glomerular filtration rate < 30 mL/min, impaired group) and 13 patients with normal graft function (glomerular filtration rate < 70 mL/min, control group), at a steady mycophenolic acid plasma level, during the first month after transplant. All patients received a fixed dose of mycophenolate mofetil (1 g twice daily) in combination with cyclosporine and steroids. Mycophenolic acid plasma levels were determined by a validated high-performance liquid chromatography method. Mycophenolic acid area under the time concentration curve from 0 to 12 hours and apparent mycophenolic acid plasma clearance (CL/f) were measured for each patient.


RESULTS
Mycophenolic acid area under the time-concentration curve (0-12 h), mycophenolic acid area under the time-concentration curve (6-10 h), first peak concentration (Cmax1), and secondary peak concentration (Cmax2) were higher in the impaired group, while mycophenolic acid plasma clearance was higher in the control group (P < .05). Trough levels (C0) were similar for both groups (P < .05). There was a negative correlation between glomerular filtration rate and area under the time-concentration curve (r=-0.422, P = .04), while there was a positive correlation between glomerular filtration rate and mycophenolic acid plasma clearance (r=0.463, P = .02).


CONCLUSIONS
Mycophenolic acid pharmacokinetics parameters in normal renal function patients and severe renal impairment patients are different, and renal graft function correlates with total mycophenolic acid area under the time-concentration curve and apparent mycophenolic acid plasma clearance. However, the necessity of dosage adjustment based on renal graft function requires further studies.
Mohammadpur
Amir-Houshang
AH
Mashad University of Medical Sciences - Department of Medicinal Chemistry, Iran.
Nazemian
Fatemeh
F
Abtahi
Bahareh
B
Naghibi
Massih
M