Pharmacokinetics of prolonged-release tacrolimus versus immediate-release tacrolimus in de novo liver transplantation: A randomized phase III substudy
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Updated: Mar 6, 2026

Quantification of the Immunosuppressant Tacrolimus on Dried Blood Spots Using LC-MS/MS
Published on: November 8, 2015
Bo-Göran Ericzon1, Evaristo Varo2, Pavel Trunečka3
1Division of Transplantation Surgery, Karolinska University Hospital Huddinge, Stockholm, Sweden.
Background:
With the same dose of tacrolimus, lower systemic exposure on the first day of dosing has been reported for prolonged-release tacrolimus compared with immediate-release tacrolimus, prompting investigation of differing initial doses.
Methods:
This substudy of a double-blind, randomized, phase III trial in de novo liver transplant recipients compared the pharmacokinetics of once-daily prolonged-release tacrolimus (initial dose: 0.2 mg/kg/day) versus twice-daily immediate-release tacrolimus (initial dose: 0.1 mg/kg/day) during the first 2 weeks post-transplant.
Results:
Pharmacokinetic data were analyzed from patients receiving prolonged-release tacrolimus (n=13) and immediate-release tacrolimus (n=12). Mean systemic exposure (AUC0-24 ) was higher with prolonged-release versus immediate-release tacrolimus. Dose-normalized AUC0-24 (normalized to 0.1 mg/kg/day) showed generally lower exposure with prolonged-release tacrolimus versus immediate-release tacrolimus. There was good correlation between AUC0-24 and concentration at 24 hours after the morning dose (r=.96 and r=.86, respectively), and the slope of the line of best fit was similar for both formulations.
Conclusions:
Doubling the initial starting dose of prolonged-release tacrolimus compared with immediate-release tacrolimus overcompensated for lower exposure on Day 1. A 50% higher starting dose of prolonged-release tacrolimus than immediate-release tacrolimus may be required for similar systemic exposure. However, doses of both formulations can be optimized using the same trough-level monitoring system. (ClinicalTrials.gov number: NCT00189826).
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