Pharmacokinetics of mycophenolate mofetil in stable pediatric liver transplant recipients receiving mycophenolate mofetil and cyclosporine

✍ Scribed by Steven J. Lobritto; Philip Rosenthal; Rene Bouw; Mimi Leung; Paul Snell; Richard D. Mamelok

• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: English
• Weight: 152 KB
• Volume: 13
• Category: Article
• ISSN: 1527-6465
• DOI: 10.1002/lt.21274

✦ Synopsis

There are few pharmacokinetic data for mycophenolate mofetil (MMF) when used in combination with cyclosporine (CsA) in pediatric liver transplant recipients. The aim of this study was to assess the pharmacokinetics of MMF in stable pediatric liver transplant patients and estimate the dose of MMF required to provide a mycophenolic acid (MPA) exposure similar to that observed in adult liver transplant recipients receiving the recommended dose of MMF (target area under the plasma concentration-time curve from 0 to 12 hours [AUC 0 -12 ] for MPA of 29 g⅐hour/mL in the immediate posttransplantation period and 58 g⅐hour/mL after 6 months). A 12-hour pharmacokinetic profile was collected for 8 pediatric patients (mean age 20.9 months) on stable doses of MMF and CsA who had received a liver transplant Ն6 months prior to entry and who had started on MMF within 2 weeks of transplantation. Mean MMF dosage was 285 mg/m 2 (range, 200-424 mg/m 2 ). Of 8 patients, 7 had a MPA AUC 0-12 (range, 11.0-37.2 g⅐hour/mL) well below the target. One patient had an AUC 0-12 Ն58 g⅐hour/mL but was considered an outlier and was excluded from analyses. Mean MPA AUC 0-12 and maximum plasma concentration values were 22.7 Ϯ 10.5 g⅐hour/mL and 7.23 Ϯ 3.27 g/mL, respectively; values normalized to 600 mg/m 2 (the approved pediatric dose in renal transplantation) were 47.0 Ϯ 21.8 g⅐hour/mL and 14.5 Ϯ 4.21 g/mL. In conclusion, assuming that MPA exhibits linear pharmacokinetics, when used in combination with CsA, a MMF dose of 740 mg/m 2 twice daily would be recommended in pediatric liver transplant recipients to achieve MPA exposures similar to those observed in adult liver transplant recipients. This finding should be confirmed by a prospective trial.