Pharmacokinetics of prolonged-release tacrolimus versus immediate-release tacrolimus in de novo liver transplantation: A randomized phase III substudy
Jazyk angličtina Země Dánsko Médium print-electronic
Typ dokumentu klinické zkoušky, fáze III, srovnávací studie, časopisecké články, multicentrická studie, randomizované kontrolované studie, práce podpořená grantem
PubMed
28295581
DOI
10.1111/ctr.12958
Knihovny.cz E-zdroje
- Klíčová slova
- calcineurin inhibitor, immunosuppressant, liver transplantation, living donor, pharmacokinetics/pharmacodynamics, rejection, tacrolimus,
- MeSH
- dvojitá slepá metoda MeSH
- imunosupresiva aplikace a dávkování farmakokinetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- následné studie MeSH
- plocha pod křivkou MeSH
- pooperační komplikace MeSH
- přežívání štěpu účinky léků MeSH
- prognóza MeSH
- rejekce štěpu farmakoterapie etiologie metabolismus MeSH
- rizikové faktory MeSH
- takrolimus aplikace a dávkování farmakokinetika MeSH
- transplantace jater škodlivé účinky MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze III MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
- srovnávací studie MeSH
- Názvy látek
- imunosupresiva MeSH
- takrolimus MeSH
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).
Clinical Services NUVISAN GmbH Neu Ulm Germany
Department of Surgery Ospedale Giovanni XXIII Bergamo Italy
Division of Abdominal and Transplantation Surgery ISMETT Palermo Italy
Division of Transplantation Surgery Karolinska University Hospital Huddinge Stockholm Sweden
Liver Transplant Unit Cruces University Hospital Baracaldo Bilbao Spain
Liver Transplant Unit King's College Hospital London UK
Liver Transplant Unit University Hospital Santiago de Compostela Santiago de Compostela Spain
Medical affairs Astellas Pharma Europe Ltd Chertsey UK
Transplantcentre Institute for Clinical and Experimental Medicine Prague Czech Republic
Citace poskytuje Crossref.org
ClinicalTrials.gov
NCT00189826
