Once-Daily MeltDose Tacrolimus Formulation and Renal Function in Caucasian Fast Tacrolimus Metabolizers: Does Early Identification Have an Impact in PK Sensitive Patients?
1University Hospital of Münster, Münster, Germany
2David Geffen School of Medicine at UCLA, Los Angeles
3Veloxis Pharmaceuticals, Cary
4Clinical Statistics Consulting, Norrystown
5Chiesi Farmaceutici S.p.A., Parma, Italy
6Charité
Universitatsmedizin, Berlin, Germany.
Meeting: 2018 American Transplant Congress
Abstract number: C70
Keywords: Immunosuppression, Kidney transplantation, Renal function
Session Information
Session Name: Poster Session C: Kidney Immunosuppression: Novel Regimens and Drug Minimization
Session Type: Poster Session
Date: Monday, June 4, 2018
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Hall 4EF
Tacrolimus (TAC) nephrotoxicity can be seen even at low blood trough levels, with factors beyond trough levels potentially contributing. TAC fast metabolizers have higher Cmax, and are at higher risk of worse renal function, BKV nephropathy, CNI toxicity and mortality as compared to regular metabolizers. The concentration over total daily dose (C/D) ratio has been suggested as a surrogate marker for TAC metabolic rates (a lower value representing more rapid metabolism). Envarsus® (LCPT) is a MeltDose® formulation of TAC with improved bioavailability, reduced Cmax and reduced peak-to-trough fluctuations, features that might be beneficial for PK sensitive patients such as TAC fast metabolizers.
C/D ratio at days 14 (D14) or 30 (D30) was used to divide the Caucasian population of a phase III study in de novo kidney transplant recipients (Budde 2014) in tertiles.Renal function (change from 1 month baseline;CFB) was compared in fast metabolizers between Prograf® (TacIR) and LCPT after 12 (M12) and 24 months (M24).
The C/D ratio of fast metabolizers was higher for LCPT vs. TacIR at both D14 (0.83 vs. 0.76 ng/mL*1/mg) and D30 (0.98 vs. 0.87 ng/mL*1/mg). After stratification at both D14 and D30, absolute eGFR at M12 and M24 was similar although numerically lower for TacIR. D14-stratified eGFR CFB was similar at M12 with LCPT vs. TacIR (5.38±2.63 vs. 4.94±2.19 mL/min*1.73m2), and significantly higher at M24 (12.33±2.68 vs. 4.58±2.53 ml/min*1.73m2;p=0.04). D30-stratfied CFB was higher for LCPT already at M12 (7.26±2.43 vs. 2.96±2.24 mL/min*1.73m2), and increased at M24 (8.23±3.30 vs 2.54±2.31 mL/min*1.73m2), albeit not reaching statistical significance.
Caucasian fast metabolizers showed improved eGFR CFB when treated with LCPT as compared to TacIR, supporting the hypothesis that the flatter PK of LCPT might be beneficial in these PK sensitive patients likely experiencing higher peak levels. Early identification seems to lead to a greater benefit, possibly due to reduced time spent in the higher range. These interesting results warrant further confirmation in prospective clinical trials.
CITATION INFORMATION: Budde K., Suwelack B., Stevens D., Du W., Procaccianti C., Maas C., Bunnapradist S. Once-Daily MeltDose Tacrolimus Formulation and Renal Function in Caucasian Fast Tacrolimus Metabolizers: Does Early Identification Have an Impact in PK Sensitive Patients? Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:
Budde K, Suwelack B, Stevens D, Du W, Procaccianti C, Maas C, Bunnapradist S. Once-Daily MeltDose Tacrolimus Formulation and Renal Function in Caucasian Fast Tacrolimus Metabolizers: Does Early Identification Have an Impact in PK Sensitive Patients? [abstract]. https://atcmeetingabstracts.com/abstract/once-daily-meltdose-tacrolimus-formulation-and-renal-function-in-caucasian-fast-tacrolimus-metabolizers-does-early-identification-have-an-impact-in-pk-sensitive-patients/. Accessed May 16, 2025.« Back to 2018 American Transplant Congress