title: Conversion from Prograf to Advagraf in stable paediatric renal transplant patients and 1-year follow-up.
abstract: BACKGROUND
  The conversion from Prograf to Advagraf on a 1:1 (mg:mg) basis has been questioned in light of the publication of studies showing a decrease in tacrolimus blood concentrations after the administration of Advagraf.
  
  
  METHODS
  The bioavailability of Prograf and Advagraf was evaluated in an open-label conversion study in 21 stable renal transplant paediatric patients. Serial blood samples for determining tacrolimus levels were collected during a 24-h period before (on Prograf) and after (on Advagraf) conversion. Tacrolimus pharmacokinetic parameters were calculated using a non-compartmental approach and the relative bioavailability calculated. Clinical and analytical data were obtained at 30, 90, 180 and 360 days after study enrolment.
  
  
  RESULTS
  The mean ratio and 90 % confidence interval (CI) for peak plasma drug concentration (C(max)) and the area under the time-concentration curve during the first 24 h (AUC(0-24)) were 81.54 (95 % CI 71.6-92.87) and 87.19 (95 % CI 79.91-95.13), respectively. Renal glomerular filtration rate remained stable over the course of the follow-up. Two patients presented clinical events unrelated to tacrolimus. Tacrolimus levels decreased in the first month, the dose/level ratio increased between months 1 and 6 and slight dose adjustments were required during the follow-up period.
  
  
  CONCLUSIONS
  Our results show that Advagraf bioequivalence cannot be ensured in this population. Significant changes in tacrolimus levels and dose were observed on long-term follow-up.
authors.affiliation: Clinical Pharmacology Service, University Hospital La Paz, Paseo de la Castellana, 261, 28046, Madrid, Spain, antonio.carcas@uam.es.
authors.forename: Antonio J
authors.initials: AJ
authors.lastname: Carcas-Sansuán
authors.forename: Laura
authors.initials: L
authors.lastname: Espinosa-Román
authors.forename: Gonzalo N
authors.initials: GN
authors.lastname: Almeida-Paulo
authors.forename: Angel
authors.initials: A
authors.lastname: Alonso-Melgar
authors.forename: Carmen
authors.initials: C
authors.lastname: García-Meseguer
authors.forename: Carlota
authors.initials: C
authors.lastname: Fernández-Camblor
authors.forename: Nicolás
authors.initials: N
authors.lastname: Medrano
authors.forename: Elena
authors.initials: E
authors.lastname: Ramirez
mesh_terms: D000293:Adolescent; D019540:Area Under Curve; D001682:Biological Availability; D002648:Child; D002675:Child, Preschool; D003692:Delayed-Action Preparations; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016030:Kidney Transplantation; D008297:Male; D016559:Tacrolimus / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use
chemical_list: D003692:Delayed-Action Preparations; D007166:Immunosuppressive Agents; D016559:Tacrolimus
references.citation: Drugs. 2011 Aug 20;71(12):1561-77
references.pmid: 21861541
references.citation: Transplant Proc. 2011 May;43(4):1024-7
references.pmid: 21620042
references.citation: Clin Transplant. 2010 Mar-Apr;24(2):213-22
references.pmid: 19674014
references.citation: Drugs. 2007;67(13):1931-43
references.pmid: 17722962
references.citation: Transplantation. 2012 Feb 15;93(3):241-3
references.pmid: 22234346
references.citation: Transplantation. 1995 Nov 15;60(9):914-20
references.pmid: 7491693
references.citation: Transplantation. 2004 Mar 15;77(5):769-76
references.pmid: 15021846
references.citation: Pediatr Transplant. 2010 Aug;14(5):603-13
references.pmid: 20214741
references.citation: Clin Transplant. 2011 Nov-Dec;25(6):864-70
references.pmid: 21077956
references.citation: Transplantation. 2010 Sep 15;90(5):523-9
references.pmid: 20592652
references.citation: Transpl Int. 2005 Oct;18(10):1121-33
references.pmid: 16162098
references.citation: Arch Intern Med. 1990 Sep;150(9):1881-4
references.pmid: 2102668
references.citation: J Am Soc Nephrol. 2005 Jun;16(6):1839-48
references.pmid: 15800121
references.citation: Transplant Proc. 2012 Jan;44(1):128-33
references.pmid: 22310596
references.citation: Transplantation. 2013 Jan 27;95(2):333-40
references.pmid: 23263559
references.citation: Adv Ren Replace Ther. 1997 Jan;4(1):46-54
references.pmid: 8996620
references.citation: Transplantation. 2011 Mar 15;91(5):566-9
references.pmid: 21192316
references.citation: Transpl Int. 2012 Mar;25(3):283-93
references.pmid: 22239105
references.citation: Transplantation. 2007 Apr 15;83(7):858-73
references.pmid: 17460556
references.citation: Transplant Proc. 2011 May;43(4):1028-9
references.pmid: 21620043
references.citation: J Heart Lung Transplant. 1996 Jun;15(6):631-45
references.pmid: 8794030
references.citation: Ther Drug Monit. 2012 Feb;34(1):46-52
references.pmid: 22249344
references.citation: Transplantation. 1995 Feb 15;59(3):340-7
references.pmid: 7871562
references.citation: Transplant Proc. 2009 Jul-Aug;41(6):2115-7
references.pmid: 19715848