Comparison of mycophenolic acid pharmacokinetic parameters in kidney transplant patients within the first 3 months post-transplant

• Published in: Journal of clinical pharmacy and therapeutics Vol. 31; no. 1; pp. 27 - 34
• Main Authors: Pawinski, T., Durlik, M., Szlaska, I., Urbanowicz, A., Majchrnak, J., Gralak, B.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-02-2006; Blackwell; Hindawi Limited
• Subjects: Adolescent; Adult; Area Under Curve; Biological and medical sciences; Creatinine - classification; Cyclosporine - therapeutic use; Female; Glucuronides - blood; Graft Rejection - prevention & control; Hematocrit; Humans; immunosuppressive agents; Immunosuppressive Agents - blood; Immunosuppressive Agents - pharmacokinetics; Immunosuppressive Agents - therapeutic use; Kidney Transplantation; Leukocyte Count; Male; Medical sciences; Middle Aged; mycophenolic acid; Mycophenolic Acid - analogs & derivatives; Mycophenolic Acid - blood; Mycophenolic Acid - pharmacokinetics; Mycophenolic Acid - therapeutic use; pharmacokinetics; Pharmacology. Drug treatments; receiver operating characteristic curve analysis; renal transplant; Tacrolimus - therapeutic use; Time Factors; Human; Mycophenolic acid; renal transplant; Transplantation; Kidney; Immunomodulator; immunosuppressive agents; Treatment; Urinary system; Surgery; Receiver operating characteristic curves; Graft; Parameter; Immunosuppressive agent; receiver operating characteristic curve analysis; Pharmacokinetics; Comparative study
• ISSN: 0269-4727; 1365-2710
• DOI: 10.1111/j.1365-2710.2006.00713.x

Summary
Objective:  The aim of this study was to investigate the effect of time on pharmacokinetic (PK) parameters of mycophenolic acid (MPA) in the early post‐transplant period in kidney recipients. MPA is the active metabolite of mycophenolate mofetil (MMF), which was introduced into clinical practice ten years ago.
Method:  Mycophenolate mofetil was co‐administered with cyclosporin (CsA) in a subgroup of 23 patients and with tacrolimus (Tac) in a subgroup of 10 patients. MPA plasma concentration profiles were measured by a validated high performance liquid chromatography method 1 week, 2 and 3 months after transplantation.
Results:  Despite a comparable MMF dose, a large inter‐patient variability in both MPA area under the curve (AUC) from 0 to 12 h (range 10·03–135·4 μg h/mL) and in predose concentrations (0·31–6·09 μg/mL) was observed. Patients with AUC > 35 μg h/mL showed better (P < 0·1) renal function than patients with AUC < 20 μg h/mL (mean creatinine concentration 1·48 ± 0·12 vs. 3·35 ± 0·4 mg/dL respectively). The total MPA trough and AUC did not correlate with biochemical parameters: leucocyte cell count and haematocrit. A higher trough level of the metabolite MPA glucuronide (MPAG) in the 1 week after transplantation was found when compared with the 3‐month level (mean 150·1 ± 146·7; range 17·1 to 560 vs. 75·8 ± 40·0; range 27·3 to 174·2 μg/mL). The concentration of MPA, and MPA AUC values were significantly lower in patients receiving MMF and CsA than those receiving MMF and Tac during all three periods studied (P < 0·02). The influence of C0 and MPA AUC values on the risk of graft rejection was investigated using receiver operating characteristic (ROC) curve analysis. The area under the ROC curve for AUC was 0·847, whereas that of C0 was 0·632.
Conclusions:  The MPA AUC0−12h appeared to be the more effective PK parameter for predicting acute rejection. We recommend that routine MPA and MPAG therapeutic drug level monitoring should be an important part of MMF therapy.