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Pharmacokinetics of mycophenolate mofetil in stable pediatric liver transplant recipients receiving mycophenolate mofetil and cyclosporine
Author(s) -
Lobritto Steven J.,
Rosenthal Philip,
Bouw Rene,
Leung Mimi,
Snell Paul,
Mamelok Richard D.
Publication year - 2007
Publication title -
liver transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.814
H-Index - 150
eISSN - 1527-6473
pISSN - 1527-6465
DOI - 10.1002/lt.21274
Subject(s) - mycophenolate , medicine , pharmacokinetics , mycophenolic acid , liver transplantation , urology , area under the curve , transplantation , gastroenterology , therapeutic drug monitoring , pharmacology
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 μg·hour/mL in the immediate posttransplantation period and 58 μg·hour/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 ≥6 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 μg·hour/mL) well below the target. One patient had an AUC 0‐12 ≥58 μg·hour/mL but was considered an outlier and was excluded from analyses. Mean MPA AUC 0‐12 and maximum plasma concentration values were 22.7 ± 10.5 μg·hour/mL and 7.23 ± 3.27 μg/mL, respectively; values normalized to 600 mg/m 2 (the approved pediatric dose in renal transplantation) were 47.0 ± 21.8 μg·hour/mL and 14.5 ± 4.21 μg/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. Liver Transpl 13:1570–1575, 2007. © 2007 AASLD.