# name
Optimizing dose conversion from IR-Tac to LCP-Tac formulations in renal transplant recipients: A population pharmacokinetic modeling study

# metadata.dc.description.abstract[].value
Background/Objectives: Tacrolimus dosing remains challenging due to its narrow therapeutic index and high inter- and intra-patient variability. The extended-release once-daily tacrolimus (LCP-Tac) formulation provides enhanced bioavailability and a sustained pharmacokinetic profile compared to the immediate-release twice-daily tacrolimus (IR-Tac) formulation. Although a general conversion ratio of 1:0.7 is widely recommended when switching between formulations, current guidelines do not account for pharmacogenetic variability. This study aimed to determine whether CYP3A5 genotype influences the conversion ratio in Caucasian renal transplant recipients using population pharmacokinetic (PopPK) modeling. Methods: A PopPK model was developed in NONMEM using full PK profiles (10-18 samples per patient) from 30 stable renal transplant patients treated with both IR-Tac and LCP-Tac. Results: Tacrolimus pharmacokinetics were best described by a two-compartment model with first-order absorption and linear elimination with distinct absorption rate constants and lag times for each formulation. Including circadian rhythm in the apparent clearance (CL/F) and Ka of IR-Tac significantly improved the model. CYP3A5 polymorphism was the most powerful covariate explaining variability on CL/F. CYP3A5*1 expressers showed higher clearance and lower exposure requiring a more pronounced dose reduction upon conversion to LCP-Tac. Simulations indicated optimal conversion ratios of 1:0.6 for CYP3A5*1 expressers and 1:0.7 for non-expressers. Conclusions: These findings highlight the need to move beyond a one-size-fits-all conversion ratio and adopt genotype-informed strategies. LCP-Tac's enhanced bioavailability requires dose reduction, greater in expressers when switching from IR-Tac. These genotype-specific recommendations provide clinically actionable guidance to complement therapeutic drug monitoring and support more individualized conversion protocols in renal transplantation.

# metadata.dc.rights[].value
cc-by (c)  Mohammed Ali, Z. et al., 2025

# metadata.dc.source[].value
Articles publicats en revistes (Infermeria Fonamental i Clínica)

# metadata.dc.title[].value
Optimizing dose conversion from IR-Tac to LCP-Tac formulations in renal transplant recipients: A population pharmacokinetic modeling study