Mycophenolate Mofetil Pharmacokinetic Monitoring in Pediatric Kidney Transplant Recipients

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• 作者：Ghio ; L. ; Ferraresso ; M. ; Viganò ; S.M. ; Ginevri ; F. ; Perfumo ; F. ; Gianoglio ; B. ; Murer ; L. ; et. al.
• 刊名：Transplantation Proceedings
• 出版年：2005
• 出版时间：March, 2005
• 年：2005
• 卷：37
• 期：2
• 页码：856-858
• 全文大小：67.3 K

文摘

This open-label, longitudinal, long-term study of de novo pediatric renal transplant recipients was designed to investigate the pharmacokinetics (PK) of mycophenolic acid (MPA) and its possible interaction with cyclosporine (CsA). Thirty-four children on an immunosuppressive regimen of CsA, prednisone, and mycophenolate mofetil (MMF, 300–400 mg/m² twice daily) were investigated at 6, 30, 180, and 360 days after transplantation. Considerable interindividual variability in the areas under the concentration curve (AUCb>(0–12)b>) of MPA was observed during the follow-up, although the dose of MMF remained the same over the same time. Predose levels (C0) increased significantly during the first 6 months after transplantation: C0 at 6 and 180 days after transplantation was 0.8 &#xb1; 0.6 and 1.9 &#xb1; 1.1 bc;g/mL (P < .0001). A significant time-dependent increase in the AUC of MPA was also observed during the first 6 posttransplant months: AUCb>(0–12)b> at 6 and 180 days after transplantation was 23.3 &#xb1; 10.8 and 40 &#xb1; 11.6 mg*h/L (P = .003). MPA concentrations 3 and 4 hours after MMF intake were the individual time points that best correlated with the full MPA AUC (r = 0.8 and 0.79; P < .001). The abbreviated MPA AUC (0–4 hours) correlated reasonably with the full AUC (r = 0.87; P < .001). Finally, a significant reduction in CsA dose during the first 6 posttransplant months (P < .001) matched the significant increases in both MPA C0 and full MPA AUC, thus demonstrating the interaction of the 2 immunosuppressive drugs. These observations suggest the need for therapeutic drug monitoring when adjusting the dose of MMF in children.