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).

• 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