title: Mycophenolate sodium dosing in combination with tacrolimus: pharmacokinetic evaluation of a novel regimen in de novo tacrolimus-treated kidney transplant patients.
abstract: BACKGROUND
  There are no clear guidelines concerning the appropriate dose of mycophenolate acid (MPA) to be used in association with tacrolimus. When MPA is given at an approved fixed dose in cyclosporine-treated patients, initial systemic under exposure is frequent and associated with the occurrence of acute rejection. We pharmacologically evaluated in tacrolimus-treated recipients a novel dosing regimen of MPA with an initial high dose followed by a gradual decrease over time.
  
  
  METHODS
  15 de novo tacrolimus-treated kidney transplant patients were administered mycophenolate sodium at the dose of 720 mg b.i.d. for the first week post-transplant, 540 mg b.i.d. until Day 30, and then 360 mg b.i.d. until Day 90. MPA exposure was evaluated by the 12 h area under MPA concentration versus time curve (AUC) determined at Days 2, 7, 15, 30 and 90 post-transplant.
  
  
  RESULTS
  Median MPA AUC was constantly within the therapeutic window of 30 - 60 mg/l × h throughout the three months of evaluation. More than 75% of patients had a MPA AUC above 30 mg/l × h at Day 2 and Day 7 post-transplant.
  
  
  CONCLUSIONS
  This exploratory study suggests that such a dosing regimen of mycophenolate sodium might quickly offer and sustain an optimal exposure to MPA in tacrolimus-treated kidney transplant patients.
authors.affiliation: Université Jean MONNET, Saint-Etienne, France. betrand.pons@chu-st-etienne.fr
authors.forename: Bertrand
authors.initials: B
authors.lastname: Pons
authors.forename: Xavier
authors.initials: X
authors.lastname: Delavenne
authors.forename: Manolie
authors.initials: M
authors.lastname: Mehdi
authors.forename: Nicolas
authors.initials: N
authors.lastname: Maillard
authors.forename: Catherine
authors.initials: C
authors.lastname: Sauron
authors.forename: François
authors.initials: F
authors.lastname: Berthoux
authors.forename: Eric
authors.initials: E
authors.lastname: Alamartine
authors.forename: Thierry
authors.initials: T
authors.lastname: Basset
authors.forename: Christophe
authors.initials: C
authors.lastname: Mariat
mesh_terms: D000328:Adult; D000368:Aged; D019540:Area Under Curve; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D005260:Female; D005602:France; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D016030:Kidney Transplantation / Q000009:adverse effects / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D010865:Pilot Projects; D011446:Prospective Studies; D016559:Tacrolimus / Q000008:administration & dosage / Q000493:pharmacokinetics*; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D016559:Tacrolimus