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.
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: Katherine A Barraclough; Nicole M Isbel; David W Johnson; Scott B Campbell; Christine E Staatz Journal: Drugs Date: 2011-08-20 Impact factor: 9.546
Authors: M Crespo; M Mir; M Marin; S Hurtado; C Estadella; X Gurí; O Rap; R Moral; J M Puig; J Lloveras Journal: Transplant Proc Date: 2009 Jul-Aug Impact factor: 1.066
Authors: G N Almeida-Paulo; I Dapía García; R Lubomirov; A M Borobia; N L Alonso-Sánchez; L Espinosa; A J Carcas-Sansuán Journal: Pharmacogenomics J Date: 2017-01-17 Impact factor: 3.550
Authors: Jacek Rubik; Dominique Debray; Deirdre Kelly; Franck Iserin; Nicholas J A Webb; Piotr Czubkowski; Karel Vondrak; Anne-Laure Sellier-Leclerc; Christine Rivet; Silvia Riva; Burkhard Tönshoff; Lorenzo D'Antiga; Stephen D Marks; Raymond Reding; Gbenga Kazeem; Nasrullah Undre Journal: Transpl Int Date: 2019-08-27 Impact factor: 3.782