Browsing by Author "Mohammadpur, Amir-Houshang"

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    Influence of Renal Graft Function on Mycophenolic Acid Pharmacokinetics During the Early Period After Kidney Transplant
    (Başkent Üniversitesi, 2008-12) Mohammadpur, Amir-Houshang; Naghibi, Massih; Abtahi, Bahareh; Nazemian, Fatemeh
    Objectives: 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. Materials and 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.
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    Pharmacokinetics of Mycophenolic Acid During the Early Period After Renal Transplant
    (Başkent Üniversitesi, 2007-12) Nazemian, Fatemeh; Mohammadpur, Amir-Houshang; Abtahi, Bahareh; Naghibi, Massih
    Objectives: 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 with mycophenolic acid pharmacokinetics during the early posttransplant period. Patients and 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.