title: Optimization of the dosing regimen of mycophenolate mofetil in pediatric liver transplant recipients.
abstract: Mycophenolate mofetil (MMF) is now commonly used in pediatric liver transplant recipients, but no clear recommendations about the dosing regimen have been made for this population. The aim of this study was to determine the MMF dosage required for pediatric liver transplant recipients to achieve an area under the plasma concentration-time curve from 0 to 12 hours (AUC(0-12) ) for mycophenolic acid (MPA) greater than 30 mg hour/L. A pharmacokinetic study of 15 children (median age = 8.3 years, range = 1.1-15.2 years) was performed at a median of 11.0 months (range = 0.5-88.0 months) after liver transplantation. MMF was initially introduced at a median starting dose of 300 mg/m(2) twice a day (range = 186-554 mg/m(2) twice a day). Thirteen of the 15 patients had an MPA AUC(0-12) value less than 30 mg hour/L. The MMF dosage had to be increased in all patients except 1. The MMF dosage required to reach an MPA AUC(0-12) value greater than the defined target of 30 mg hour/L ranged from 371 to 1014 mg/m(2) /day. For 2 patients who received rifampin in addition to MMF, the MPA AUC(0-12) value remained low despite a 2-fold increase in the MMF dosage. In conclusion, an initial MMF dose of 600 mg/m(2) twice a day led to MPA AUC(0-12) values greater than the 30 mg hour/L threshold except when rifampin was coadministered. Because of the important interindividual variability of MPA pharmacokinetics, therapeutic drug monitoring is recommended for optimizing the daily MMF dosage. Furthermore, these results suggest that the coadministration of MPA with rifampin should be avoided.
authors.affiliation: Department of Clinical Pharmacy, Bicetre Hospital, Assistance Publique-Hôpitaux de Paris, Le Kremlin Bicêtre, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Barau
authors.forename: Aurélie
authors.initials: A
authors.lastname: Barrail-Tran
authors.forename: Bogdan
authors.initials: B
authors.lastname: Hemerziu
authors.forename: Dalila
authors.initials: D
authors.lastname: Habes
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Taburet
authors.forename: Dominique
authors.initials: D
authors.lastname: Debray
authors.forename: Valérie
authors.initials: V
authors.lastname: Furlan
mesh_terms: D000293:Adolescent; D000367:Age Factors; D000982:Antipruritics / Q000008:administration & dosage; D019540:Area Under Curve; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000008:administration & dosage; D004334:Drug Administration Schedule; D054796:Drug Dosage Calculations; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D007223:Infant; D016031:Liver Transplantation / Q000276:immunology*; D008297:Male; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D010297:Paris; D011241:Prednisone / Q000008:administration & dosage; D012293:Rifampin / Q000008:administration & dosage; D016559:Tacrolimus / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D000982:Antipruritics; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid; D011241:Prednisone; D012293:Rifampin; D016559:Tacrolimus