Pharmacokinetic Study of Conversion between 2 Formulations of Once-daily Extended-release Tacrolimus in Stable Lung Transplant Patients

Helena Sintes, Berta Sáez-Giménez, Cristina Berastegui, Manuel López-Meseguer, Víctor Monforte, Carlos Bravo, Jaume Vima, Susana Gómez-Ollés, Antonio Roman

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1 Citation (Scopus)

Abstract

© 2018 Wolters Kluwer Health, Inc. All rights reserved. Background The aim of this study was to compare the pharmacokinetic profile, tolerability, and safety of a novel once-daily extended-release formulation of tacrolimus (LCPT) with that of once-daily prolonged-release tacrolimus (ODT) in stable adult lung transplant (LT) recipients. Methods Phase II, open-label, single-arm, single-center, prospective pilot pharmacokinetic study. Study population comprised 20 stable LT recipients receiving ODT, mean age 55.9 years (range, 38-67 years), 13 (65%) men. Patients were switched to LCPT in a 1:0.7 (mg/mg) conversion dose. Follow-up was 6 months, and cystic fibrosis patients were excluded. Two 24-hour pharmacokinetic profiles were obtained for each patient, the first on day -14 and the second on day +14 after switching to LCPT. Pharmacokinetic parameters and safety were compared. Results Mean (SD) area under the concentration-time curve from 0 to 24 hours was 253.97 (61.90) ng/mL per hour for ODT and 282.44 (68.2) ng/mL per hour for LCPT. Systemic exposure was similar in both (Schuirmann two 1-sided test). Mean (SD) dose was 5.05 (1.67) mg in ODT and 3.36 (1.03) mg in LCPT (P = 0.0002). Time to maximum concentration was 125 minutes for ODT and 325 minutes for LCPT (P < 0.001). Correlation between area under the concentration-time curve from 0 to 24 hours and C24 was 0.896 (r 2 ) for ODT and 0.893 (r 2 ) for LCPT. There were no differences in adverse effects. At 6 months, conversion dose was 1:0.59 (mg/mg) in patients with unchanged minimum plasma concentration target levels. Conclusions Switching from ODT to LCPT was safe and well tolerated in stable LT recipients without cystic fibrosis. A significantly lower dose of LCPT allows similar bioavailability. A conversion ratio 1:0.6 could be enough to maintain similar target levels.
Original languageEnglish
Pages (from-to)e439-e446
JournalTransplantation
Volume102
DOIs
Publication statusPublished - 1 Oct 2018

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