Pharmacokinetics of prolonged-release tacrolimus versus immediate-release tacrolimus in de novo liver transplantation: A randomized phase III substudy

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023001%3A_____%2F17%3A00075980" target="_blank" >RIV/00023001:_____/17:00075980 - isvavai.cz</a>

Result on the web

<a href="http://onlinelibrary.wiley.com/doi/10.1111/ctr.12958/full" target="_blank" >http://onlinelibrary.wiley.com/doi/10.1111/ctr.12958/full</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1111/ctr.12958" target="_blank" >10.1111/ctr.12958</a>

Result language

angličtina

Original language name

Pharmacokinetics of prolonged-release tacrolimus versus immediate-release tacrolimus in de novo liver transplantation: A randomized phase III substudy

Original language description

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.govnumber:NCT00189826).

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

30213 - Transplantation

Project

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Continuities

N - Vyzkumna aktivita podporovana z neverejnych zdroju

Publication year

2017

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Clinical transplantation

ISSN

0902-0063

e-ISSN

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Volume of the periodical

31

Issue of the periodical within the volume

6

Country of publishing house

US - UNITED STATES

Number of pages

7

Pages from-to

"art. no. e12958"

UT code for WoS article

000404975900004

EID of the result in the Scopus database

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