AUTHOR=Monchaud Caroline , Woillard Jean-Baptiste , Crépin Sabrina , Tafzi Naïma , Micallef Ludovic , Rerolle Jean-Philippe , Dharancy Sébastien , Conti Filomena , Choukroun Gabriel , Thierry Antoine , Buchler Matthias , Salamé Ephrem , Garrouste Cyril , Duvoux Christophe , Colosio Charlotte , Merville Pierre , Anglicheau Dany , Etienne Isabelle , Saliba Faouzi , Mariat Christophe , Debette-Gratien Marilyne , Marquet Pierre TITLE=Tacrolimus Exposure Before and After a Switch From Twice-Daily Immediate-Release to Once-Daily Prolonged Release Tacrolimus: The ENVARSWITCH Study JOURNAL=Transplant International VOLUME=36 YEAR=2023 URL=https://www.frontierspartnerships.org/journals/transplant-international/articles/10.3389/ti.2023.11366 DOI=10.3389/ti.2023.11366 ISSN=1432-2277 ABSTRACT=
LCP-tacrolimus displays enhanced oral bioavailability compared to immediate-release (IR-) tacrolimus. The ENVARSWITCH study aimed to compare tacrolimus AUC0–24 h in stable kidney (KTR) and liver transplant recipients (LTR) on IR-tacrolimus converted to LCP-tacrolimus, in order to re-evaluate the 1:0.7 dose ratio recommended in the context of a switch and the efficiency of the subsequent dose adjustment. Tacrolimus AUC0–24 h was obtained by Bayesian estimation based on three concentrations measured in dried blood spots before (V2), after the switch (V3), and after LCP-tacrolimus dose adjustment intended to reach the pre-switch AUC0–24 h (V4). AUC0–24 h estimates and distributions were compared using the bioequivalence rule for narrow therapeutic range drugs (Westlake 90% CI within 0.90–1.11). Fifty-three KTR and 48 LTR completed the study with no major deviation. AUC0–24 h bioequivalence was met in the entire population and in KTR between V2 and V4 and between V2 and V3. In LTR, the Westlake 90% CI was close to the acceptance limits between V2 and V4 (90% CI = [0.96–1.14]) and between V2 and V3 (90% CI = [0.96–1.15]). The 1:0.7 dose ratio is convenient for KTR but may be adjusted individually for LTR. The combination of DBS and Bayesian estimation for tacrolimus dose adjustment may help with reaching appropriate exposure to tacrolimus rapidly after a switch.