title: Similar MPA exposure on modified release and regular tacrolimus.
abstract: Concomitant immunosuppression may affect the mycophenolate mofetil exposure. Astellas developed a once-daily modified release formulation of tacrolimus (TacMR) with the potential to reduce the likelihood of nonadherence. It is unknown whether mycophenolic acid (MPA) area under the concentration-time curve (AUC) differs between the 2 tacrolimus (Tac) formulations. In a 2-by-2 crossover design, 20 stable renal transplant recipients on twice-daily Tac either continued their usual Tac therapy (n = 10, group 1) or switched to TacMR for a 12-week period (n = 10, group 2), after which the patients crossed over to the other formulation for another 12-week period. Pharmacokinetic profiles using limited sampling strategies were obtained before randomization (visit 1), and at 12 (visit 2) and 24 weeks (visit 3) at steady state. MPA AUC was calculated using the Pawinski formula. When analyzing visits on Tac, TacMR, and back on Tac combined, the MPA AUC for all 20 patients at baseline was 42.24 (16.98), 37.18 (13.75), and 40.09 (16.69) mg·h·L(-1), respectively, which was not statistically significant using repeated measures (P = 0.1327, R(2) = 0.1109). We conclude that MPA pharmacokinetic profiles are not altered when converting patients from Tac to TacMR.
authors.affiliation: Departments of *Medicine, Division of Nephrology; and †Pediatrics, Division of Pediatric Nephrology, Children's Hospital, London Health Science Centre and Schulich School of Medicine & Dentistry, University of Western Ontario, London, Ontario, Canada; and ‡Division of Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, University of Cincinnati; and §Department of Pediatrics, College of Medicine, University of Cincinnati, Ohio.
authors.forename: Guido
authors.initials: G
authors.lastname: Filler
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Vinks
authors.forename: Shih-Han S
authors.initials: SH
authors.lastname: Huang
authors.forename: Anthony
authors.initials: A
authors.lastname: Jevnikar
authors.forename: Norman
authors.initials: N
authors.lastname: Muirhead
mesh_terms: D000328:Adult; D000368:Aged; D019540:Area Under Curve; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D016559:Tacrolimus / Q000008:administration & dosage* / Q000494:pharmacology*
chemical_list: D003692:Delayed-Action Preparations; D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D016559:Tacrolimus