title: Conversion from twice-daily tacrolimus capsules to once-daily extended-release tacrolimus (LCPT): a phase 2 trial of stable renal transplant recipients.
abstract: BACKGROUND
  LCP-Tacro is an extended-release formulation of tacrolimus designed for once-daily dosing. Phase 1 studies demonstrated greater bioavailability to twice-daily tacrolimus capsules and no new safety concerns.
  
  
  METHODS
  In this phase 2 study, adult stable kidney transplant patients on tacrolimus capsules (Prograf) twice-daily were converted to tacrolimus tablets (LCP-Tacro) once-daily; patients continued on LCP-Tacro once-daily for days 8 to 21; trough levels were to be maintained between 5 and 15 ng/mL; 24-hr pharmacokinetic assessments were done on days 7 (baseline pre-switch), 14, and 21.
  
  
  RESULTS
  Forty-seven patients completed LCP-Tacro dosing per protocol. The mean conversion ratio was 0.71. Pharmacokinetic data demonstrated consistent exposure (AUC) at the lower conversion dose. C(max) (P = 0.0001), C(max)/C(min) ratio (P < 0.001), percent fluctuation (P < 0.0001), and swing (P = 0.0004) were significantly lower and T(max) significantly (P < 0.001) longer for LCP-Tacro versus Prograf. AUC24 and C(min) correlation coefficients after 7 and 14 days of therapy were 0.86 or more, demonstrating a robust correlation between LCP-Tacro tacrolimus exposure and trough levels. There were three serious adverse events; none were related to study drug and all were resolved.
  
  
  CONCLUSIONS
  Stable kidney transplant patients can be safely converted from Prograf twice-daily to LCP-Tacro. The greater bioavailability of LCP-Tacro allows for once-daily dosing and similar (AUC) exposure at a dose approximately 30% less than the total daily dose of Prograf. LCP-Tacro displays flatter kinetics characterized by significantly lower peak-trough fluctuations.
authors.affiliation: The Methodist Hospital, Houston, TX 77030, USA. aogaber@tmhs.org
authors.forename: A Osama
authors.initials: AO
authors.lastname: Gaber
authors.forename: Rita R
authors.initials: RR
authors.lastname: Alloway
authors.forename: Kenneth
authors.initials: K
authors.lastname: Bodziak
authors.forename: Bruce
authors.initials: B
authors.lastname: Kaplan
authors.forename: Suphamai
authors.initials: S
authors.lastname: Bunnapradist
mesh_terms: D000328:Adult; D001682:Biological Availability; D002214:Capsules; D003692:Delayed-Action Preparations; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D016030:Kidney Transplantation / Q000276:immunology / Q000502:physiology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016559:Tacrolimus / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood
chemical_list: D002214:Capsules; D003692:Delayed-Action Preparations; D007166:Immunosuppressive Agents; D016559:Tacrolimus