Back to Search
Start Over
Pharmacokinetics of prolonged-release tacrolimus versus immediate-release tacrolimus in de novo liver transplantation: A randomized phase III substudy.
- Source :
-
Clinical Transplantation . Jun2017, Vol. 31 Issue 6, pn/a-N.PAG. 7p. - Publication Year :
- 2017
-
Abstract
- 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). [ABSTRACT FROM AUTHOR]
- Subjects :
- *LIVER transplantation
*PHARMACOKINETICS
*TACROLIMUS
*CLINICAL trials
*DRUG dosage
Subjects
Details
- Language :
- English
- ISSN :
- 09020063
- Volume :
- 31
- Issue :
- 6
- Database :
- Academic Search Index
- Journal :
- Clinical Transplantation
- Publication Type :
- Academic Journal
- Accession number :
- 123394934
- Full Text :
- https://doi.org/10.1111/ctr.12958