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Conversion From Twice-Daily Tacrolimus Capsules to Once-Daily Extended-Release Tacrolimus (LCPT): A Phase 2 Trial of Stable Renal Transplant Recipients
BACKGROUND: LCP-Tacro is an extended-release formulation of tacrolimus designed for once-daily dosing. Phase 1 studies demonstrated greater bioavailability to twice-daily tacrolimus capsules and no new safety concerns. METHODS: In this phase 2 study, adult stable kidney transplant patients on tacrol...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Lippincott Williams & Wilkins
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3723088/ https://www.ncbi.nlm.nih.gov/pubmed/23715050 http://dx.doi.org/10.1097/TP.0b013e3182962cc1 |
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author | Gaber, A. Osama Alloway, Rita R. Bodziak, Kenneth Kaplan, Bruce Bunnapradist, Suphamai |
author_facet | Gaber, A. Osama Alloway, Rita R. Bodziak, Kenneth Kaplan, Bruce Bunnapradist, Suphamai |
author_sort | Gaber, A. Osama |
collection | PubMed |
description | BACKGROUND: LCP-Tacro is an extended-release formulation of tacrolimus designed for once-daily dosing. Phase 1 studies demonstrated greater bioavailability to twice-daily tacrolimus capsules and no new safety concerns. METHODS: In this phase 2 study, adult stable kidney transplant patients on tacrolimus capsules (Prograf) twice-daily were converted to tacrolimus tablets (LCP-Tacro) once-daily; patients continued on LCP-Tacro once-daily for days 8 to 21; trough levels were to be maintained between 5 and 15 ng/mL; 24-hr pharmacokinetic assessments were done on days 7 (baseline pre-switch), 14, and 21. RESULTS: Forty-seven patients completed LCP-Tacro dosing per protocol. The mean conversion ratio was 0.71. Pharmacokinetic data demonstrated consistent exposure (AUC) at the lower conversion dose. C(max) (P=0.0001), C(max)/C(min) ratio (P<0.001), percent fluctuation (P<0.0001), and swing (P=0.0004) were significantly lower and T(max) significantly (P<0.001) longer for LCP-Tacro versus Prograf. AUC(24) and C(min) correlation coefficients after 7 and 14 days of therapy were 0.86 or more, demonstrating a robust correlation between LCP-Tacro tacrolimus exposure and trough levels. There were three serious adverse events; none were related to study drug and all were resolved. CONCLUSIONS: Stable kidney transplant patients can be safely converted from Prograf twice-daily to LCP-Tacro. The greater bioavailability of LCP-Tacro allows for once-daily dosing and similar (AUC) exposure at a dose approximately 30% less than the total daily dose of Prograf. LCP-Tacro displays flatter kinetics characterized by significantly lower peak-trough fluctuations. |
format | Online Article Text |
id | pubmed-3723088 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Lippincott Williams & Wilkins |
record_format | MEDLINE/PubMed |
spelling | pubmed-37230882013-07-26 Conversion From Twice-Daily Tacrolimus Capsules to Once-Daily Extended-Release Tacrolimus (LCPT): A Phase 2 Trial of Stable Renal Transplant Recipients Gaber, A. Osama Alloway, Rita R. Bodziak, Kenneth Kaplan, Bruce Bunnapradist, Suphamai Transplantation Clinical and Translational Research BACKGROUND: LCP-Tacro is an extended-release formulation of tacrolimus designed for once-daily dosing. Phase 1 studies demonstrated greater bioavailability to twice-daily tacrolimus capsules and no new safety concerns. METHODS: In this phase 2 study, adult stable kidney transplant patients on tacrolimus capsules (Prograf) twice-daily were converted to tacrolimus tablets (LCP-Tacro) once-daily; patients continued on LCP-Tacro once-daily for days 8 to 21; trough levels were to be maintained between 5 and 15 ng/mL; 24-hr pharmacokinetic assessments were done on days 7 (baseline pre-switch), 14, and 21. RESULTS: Forty-seven patients completed LCP-Tacro dosing per protocol. The mean conversion ratio was 0.71. Pharmacokinetic data demonstrated consistent exposure (AUC) at the lower conversion dose. C(max) (P=0.0001), C(max)/C(min) ratio (P<0.001), percent fluctuation (P<0.0001), and swing (P=0.0004) were significantly lower and T(max) significantly (P<0.001) longer for LCP-Tacro versus Prograf. AUC(24) and C(min) correlation coefficients after 7 and 14 days of therapy were 0.86 or more, demonstrating a robust correlation between LCP-Tacro tacrolimus exposure and trough levels. There were three serious adverse events; none were related to study drug and all were resolved. CONCLUSIONS: Stable kidney transplant patients can be safely converted from Prograf twice-daily to LCP-Tacro. The greater bioavailability of LCP-Tacro allows for once-daily dosing and similar (AUC) exposure at a dose approximately 30% less than the total daily dose of Prograf. LCP-Tacro displays flatter kinetics characterized by significantly lower peak-trough fluctuations. Lippincott Williams & Wilkins 2013-07-27 2013-07-16 /pmc/articles/PMC3723088/ /pubmed/23715050 http://dx.doi.org/10.1097/TP.0b013e3182962cc1 Text en Copyright © 2013 by Lippincott Williams & Wilkins http://creativecommons.org/licenses/by-nc-nd/3.0 This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivitives 3.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially. |
spellingShingle | Clinical and Translational Research Gaber, A. Osama Alloway, Rita R. Bodziak, Kenneth Kaplan, Bruce Bunnapradist, Suphamai Conversion From Twice-Daily Tacrolimus Capsules to Once-Daily Extended-Release Tacrolimus (LCPT): A Phase 2 Trial of Stable Renal Transplant Recipients |
title | Conversion From Twice-Daily Tacrolimus Capsules to Once-Daily Extended-Release Tacrolimus (LCPT): A Phase 2 Trial of Stable Renal Transplant Recipients |
title_full | Conversion From Twice-Daily Tacrolimus Capsules to Once-Daily Extended-Release Tacrolimus (LCPT): A Phase 2 Trial of Stable Renal Transplant Recipients |
title_fullStr | Conversion From Twice-Daily Tacrolimus Capsules to Once-Daily Extended-Release Tacrolimus (LCPT): A Phase 2 Trial of Stable Renal Transplant Recipients |
title_full_unstemmed | Conversion From Twice-Daily Tacrolimus Capsules to Once-Daily Extended-Release Tacrolimus (LCPT): A Phase 2 Trial of Stable Renal Transplant Recipients |
title_short | Conversion From Twice-Daily Tacrolimus Capsules to Once-Daily Extended-Release Tacrolimus (LCPT): A Phase 2 Trial of Stable Renal Transplant Recipients |
title_sort | conversion from twice-daily tacrolimus capsules to once-daily extended-release tacrolimus (lcpt): a phase 2 trial of stable renal transplant recipients |
topic | Clinical and Translational Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3723088/ https://www.ncbi.nlm.nih.gov/pubmed/23715050 http://dx.doi.org/10.1097/TP.0b013e3182962cc1 |
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