Pharmacokinetics of prolonged-release tacrolimus versus immediate-release tacrolimus in de novo liver Transplantation, A randomized phase III substudy
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Pharmacokinetics of prolonged-release tacrolimus versus immediate-release tacrolimus in de novo liver Transplantation, A randomized phase III substudy. / Ericzon, Bo-Göran; Varo, Evaristo; Trunečka, Pavel; Fischer, Lutz; Colledan, Michele; Gridelli, Bruno; Valdivieso, Andrés; O'Grady, John; Dickinson, James; Undre, Nasrullah.
in: CLIN TRANSPLANT, Jahrgang 31, Nr. 6, 06.2017.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Pharmacokinetics of prolonged-release tacrolimus versus immediate-release tacrolimus in de novo liver Transplantation, A randomized phase III substudy
AU - Ericzon, Bo-Göran
AU - Varo, Evaristo
AU - Trunečka, Pavel
AU - Fischer, Lutz
AU - Colledan, Michele
AU - Gridelli, Bruno
AU - Valdivieso, Andrés
AU - O'Grady, John
AU - Dickinson, James
AU - Undre, Nasrullah
N1 - © 2017 The Authors. Clinical Transplantation Published by John Wiley & Sons Ltd.
PY - 2017/6
Y1 - 2017/6
N2 - 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).
AB - 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).
KW - Journal Article
U2 - 10.1111/ctr.12958
DO - 10.1111/ctr.12958
M3 - SCORING: Journal article
C2 - 28295581
VL - 31
JO - CLIN TRANSPLANT
JF - CLIN TRANSPLANT
SN - 0902-0063
IS - 6
ER -