title: Efficacy and Safety of Elective Conversion From Sotrastaurin (STN) to Tacrolimus (TAC) or Mycophenolate (MPS) in Stable Kidney Transplant Recipients.
abstract: This study aimed to evaluate the efficacy and safety outcomes of conversion strategies in stable kidney transplant recipients after premature termination of the sotrastaurin (STN) development program.
  
  
  
  This is an exploratory and prospective study, including 38 stable renal transplant recipients. Tacrolimus (TAC) group [STN → mycophenolate sodium (MPS)] consisted of 9 patients receiving TAC, STN, and prednisone that were converted from STN to MPS. Everolimus (EVR) group (STN → TAC) consisted of 29 patients receiving EVR, STN, and prednisone that were converted from STN to TAC.
  
  
  
  In TAC (STN → MPS) group, dose-adjusted TAC concentrations decreased from baseline to first week (2.3 ± 1.1 versus 1.5 ± 1.0 ng·mL·mg, P < 0.05). Two patients experienced a first acute rejection episode. Conversion to MPS was associated with a higher incidence of adverse events. In EVR (STN → TAC) group, dose-adjusted EVR concentrations decreased from baseline to first week (3.6 ± 2.3 ng·mL·mg versus 1.9 ± 0.8 ng·mL·mg, P < 0.01). The proportion of patients with donor-specific antibodies was lower in TAC (STN → MPS) (11%) compared to EVR (STN → TAC) (31%) before conversion. Conversion from STN to TAC was associated with a reduction in estimated glomerular filtration rate (69.6 ± 16.9 versus 61.0 ± 18.8 mL·min·1.73 m, P < 0.01) and a decreased proportion of patients with donor-specific antibodies (31% versus 14%) at 12 months.
  
  
  
  Conversion from TAC/STN to TAC/MPS or from EVR/STN to TAC/EVR was associated with significant pharmacokinetic changes in both TAC and EVR whole-blood trough concentrations due to known drug-to-drug interaction, which were associated with changes in efficacy and safety.
authors.affiliation: *Nephrology Division; †Urology Division, Hospital do Rim; ‡Pathology Department, Universidade Federal de São Paulo; and §Instituto de Imunogenética, Associação Fundo de Incentivo a Pesquisa, São Paulo, Brazil.
authors.forename: Pedro
authors.initials: P
authors.lastname: Hannun
authors.forename: Claudia
authors.initials: C
authors.lastname: Felipe
authors.forename: Alexandra
authors.initials: A
authors.lastname: Ferreira
authors.forename: Tainá
authors.initials: T
authors.lastname: Sandes-Freitas
authors.forename: Marina
authors.initials: M
authors.lastname: Cristelli
authors.forename: Wilson
authors.initials: W
authors.lastname: Aguiar
authors.forename: Marcello
authors.initials: M
authors.lastname: Franco
authors.forename: Erika
authors.initials: E
authors.lastname: Campos
authors.forename: Maria
authors.initials: M
authors.lastname: Gerbase de Lima
authors.forename: Hélio
authors.initials: H
authors.lastname: Tedesco-Silva
authors.forename: José
authors.initials: J
authors.lastname: Medina-Pestana
mesh_terms: D000328:Adult; D000906:Antibodies / Q000276:immunology; D015331:Cohort Studies; D004347:Drug Interactions; D057915:Drug Substitution; D000068338:Everolimus / Q000008:administration & dosage / Q000493:pharmacokinetics; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D016030:Kidney Transplantation / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage* / Q000009:adverse effects; D011241:Prednisone / Q000008:administration & dosage; D011446:Prospective Studies; D011758:Pyrroles / Q000008:administration & dosage* / Q000009:adverse effects; D011799:Quinazolines / Q000008:administration & dosage* / Q000009:adverse effects; D016559:Tacrolimus / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics
chemical_list: D000906:Antibodies; D007166:Immunosuppressive Agents; D011758:Pyrroles; D011799:Quinazolines; C543528:sotrastaurin; D000068338:Everolimus; D009173:Mycophenolic Acid; D011241:Prednisone; D016559:Tacrolimus