title: Mycophenolic acid 12-hour area under the curve in de novo liver transplant patients given mycophenolate mofetil at fixed versus concentration-controlled doses.
abstract: Therapeutic drug monitoring of mycophenolate mofetil (MMF) was found to be beneficial in preventing acute rejection after kidney transplantation. The aim of this pilot prospective study was to evaluate the efficacy of MMF dose adjustment in de novo liver transplant patients receiving MMF at fixed versus concentration-controlled doses [ie, adapted to mycophenolic acid (MPA) AUC0-12h] and tacrolimus during the first 12 months posttransplant. Twenty-nine patients received steroids only up to day 10, induction therapy by lymphoglobulins followed by tacrolimus and MMF. In all patients, MPA AUC0-12h were measured on posttransplant days 7 and 14 and at months 1, 2, 3, 6, and 12. From March 2006 to March 2007, 15 patients received MMF at a fixed dose of 1 g twice a day for 12 months. From April 2007 to December 2007, MMF was given to 14 patients at a dose of 1 g twice a day until day 7 and was then adapted to reach an MPA AUC0-12h target of 30-60 mg x h/L. The proportion of MPA AUC0-12h values within the target range was similar in both groups. The proportion of patients with MPA AUC0-12h below 30 mg x h/L tended to be higher in the fixed dose group within the first month posttransplant. However, MMF dose did not differ significantly between the 2 groups at any period except month 1. MPA AUC0-12h tended to be higher in the concentration-controlled group at day 14 and month 2 and was significantly so at month 1. Tacrolimus trough concentrations tended to be lower in the concentration-controlled group at all study periods and was significantly so at month 3. At 12 months posttransplant, patient and graft survivals, acute rejection rate, and adverse events were similar in both groups. We concluded that adapting the dose of MMF resulted in a significant increase in MPA AUC0-12h at month 1. There was a trend toward a lower proportion of patients with MPA AUC0-12h below 30 mg x h/L in the concentration-controlled group. No difference in outcome was found between both groups.
authors.affiliation: Department of Nephrology, Dialysis and Multi-Organ Transplantation, CHU Rangueil, Toulouse, France. kamar.n@chu-toulouse.fr
authors.forename: Nassim
authors.initials: N
authors.lastname: Kamar
authors.forename: Pierre
authors.initials: P
authors.lastname: Marquet
authors.forename: Peggy
authors.initials: P
authors.lastname: Gandia
authors.forename: Fabrice
authors.initials: F
authors.lastname: Muscari
authors.forename: Laurence
authors.initials: L
authors.lastname: Lavayssière
authors.forename: Laure
authors.initials: L
authors.lastname: Esposito
authors.forename: Joelle
authors.initials: J
authors.lastname: Guitard
authors.forename: Cindy
authors.initials: C
authors.lastname: Canivet
authors.forename: Jean Marie
authors.initials: JM
authors.lastname: Peron
authors.forename: Laurent
authors.initials: L
authors.lastname: Alric
authors.forename: Bertrand
authors.initials: B
authors.lastname: Suc
authors.forename: Franck
authors.initials: F
authors.lastname: Saint-Marcoux
authors.forename: Lionel
authors.initials: L
authors.lastname: Rostaing
mesh_terms: D000328:Adult; D000368:Aged; D002985:Clinical Protocols; D005260:Female; D014453:Glucuronosyltransferase / Q000037:antagonists & inhibitors; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D016031:Liver Transplantation; D008137:Longitudinal Studies; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D011446:Prospective Studies; D012059:Rejection, Psychology; D016559:Tacrolimus / Q000494:pharmacology*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D014453:Glucuronosyltransferase; D009173:Mycophenolic Acid; D016559:Tacrolimus