Pharmacokinetics of mycophenolic acid during the early period after renal transplant.
OBJECTIVE
Mycophenolic acid, the active metabolite of mycophenolate mofetil, is administered with cyclosporine and oral steroids to prevent acute rejection after renal transplant. The aim of this study was to investigate correlations among time after transplant, subjects' demographics, and mycophenolate mofetil dosage according to body weight withmycophenolic acid pharmacokinetics during the early posttransplant period.


METHODS
Mycophenolic acid plasma levels of 19 patients were determined by a validated high-performance liquid chromatographic method at the steady state soon after transplant when graft function was good (glomerular filtration rate = 70 mL/min). All patients received a fixed dosage of mycophenolate mofetil (1 g b.i.d.) in combination with cyclosporine and steroids. The area under the time-concentration curve (AUC) and mycophenolic acid plasma clearance were measured for each patient.


RESULTS
The AUC from zero to 12 hours and trough levels increased as the time after transplant increased (P < .05), but mycophenolic acid plasma clearance decreased over time (P = .02). There was a correlation between total body weight and the AUC (P = .01, r2 = -0.627) as well as between total body weight and mycophenolic acid clearance (P = .04, r2 = 0.555). No statistically significant differences were found regarding mycophenolic acid plasma level, AUC, and mycophenolic acid plasma clearance with regard to sex or age of the subjects (P > .05). The mycophenolate mofetil dosage according to body weight correlated positively with the AUC (P = .01, r2 = 0.628), but there was a negative correlation between total body weight and mycophenolic acid plasma clearance (P = .02, r2 = -0.604).


CONCLUSIONS
Our results demonstrate that total body weight, time after transplant, and mycophenolate mofetil dosage according to body weight affect mycophenolic acid pharmacokinetics. We suggest that mycophenolic acid pharmacokinetics monitoring is necessary to individualize mycophenolate mofetil dosing during the early posttransplant period.
Nazemian
Fatemeh
F
Department of Internal Medicine, Mashad University of Medical Sciences, Mashhad, Iran. fatemah_nazemian@yahoo.ca
Mohammadpur
Amir-Houshang
AH
Abtahi
Bahareh
B
Naghibi
Massih
M
D000293:Adolescent; D000328:Adult; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D007668:Kidney / Q000378:metabolism*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid