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Electrocardiographic Effects of a Supratherapeutic Dose of WCK 2349, a Benzoquinolizine Fluoroquinolone
The purpose of this study was to measure the electrocardiographic (ECG) effects of WCK 2349 (the L‐alanine ester prodrug of levonadifloxacin) at a supratherapeutic oral dose of 2,600 mg. A total of 48 healthy volunteers were randomized to treatment with placebo, WCK 2349, or oral moxifloxacin, 400 m...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6342240/ https://www.ncbi.nlm.nih.gov/pubmed/30369076 http://dx.doi.org/10.1111/cts.12594 |
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author | Mason, Jay W. Chugh, Rakesh Patel, Anasuya Gutte, Ranjeet Bhatia, Ashima |
author_facet | Mason, Jay W. Chugh, Rakesh Patel, Anasuya Gutte, Ranjeet Bhatia, Ashima |
author_sort | Mason, Jay W. |
collection | PubMed |
description | The purpose of this study was to measure the electrocardiographic (ECG) effects of WCK 2349 (the L‐alanine ester prodrug of levonadifloxacin) at a supratherapeutic oral dose of 2,600 mg. A total of 48 healthy volunteers were randomized to treatment with placebo, WCK 2349, or oral moxifloxacin, 400 mg, in a crossover‐designed thorough QT study. A supratherapeutic mean maximum levonadifloxacin concentration (C (max)) of 43.3 μg/mL was achieved at 3.1 hours. A therapeutic dose of 1,000 mg b.i.d. in a previous study in patients resulted in a C (max) of 17.8 μg/mL. WCK 2349 exerted no significant effect on baseline‐ and placebo‐corrected QTcF (QT interval corrected for heart rate (HR) by the Fridericia formula), QRS, or PR interval. HR was transiently accelerated by a maximum of 14.4 (95% confidence interval, 11.80–16.92) beats per minute (bpm) at 3 hours. Concentration–effect modeling predicted a mean increase of 8.0 bpm at C (max) at the standard therapeutic dose. A therapeutic dose of 1,000 mg b.i.d. of WCK 2349 is not expected to cause clinically significant ECG effects, except for a possible transient increase in HR, which seems to be clinically insignificant. |
format | Online Article Text |
id | pubmed-6342240 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-63422402019-01-24 Electrocardiographic Effects of a Supratherapeutic Dose of WCK 2349, a Benzoquinolizine Fluoroquinolone Mason, Jay W. Chugh, Rakesh Patel, Anasuya Gutte, Ranjeet Bhatia, Ashima Clin Transl Sci Research The purpose of this study was to measure the electrocardiographic (ECG) effects of WCK 2349 (the L‐alanine ester prodrug of levonadifloxacin) at a supratherapeutic oral dose of 2,600 mg. A total of 48 healthy volunteers were randomized to treatment with placebo, WCK 2349, or oral moxifloxacin, 400 mg, in a crossover‐designed thorough QT study. A supratherapeutic mean maximum levonadifloxacin concentration (C (max)) of 43.3 μg/mL was achieved at 3.1 hours. A therapeutic dose of 1,000 mg b.i.d. in a previous study in patients resulted in a C (max) of 17.8 μg/mL. WCK 2349 exerted no significant effect on baseline‐ and placebo‐corrected QTcF (QT interval corrected for heart rate (HR) by the Fridericia formula), QRS, or PR interval. HR was transiently accelerated by a maximum of 14.4 (95% confidence interval, 11.80–16.92) beats per minute (bpm) at 3 hours. Concentration–effect modeling predicted a mean increase of 8.0 bpm at C (max) at the standard therapeutic dose. A therapeutic dose of 1,000 mg b.i.d. of WCK 2349 is not expected to cause clinically significant ECG effects, except for a possible transient increase in HR, which seems to be clinically insignificant. John Wiley and Sons Inc. 2018-11-27 2019-01 /pmc/articles/PMC6342240/ /pubmed/30369076 http://dx.doi.org/10.1111/cts.12594 Text en © 2018 The Authors. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of the American Society for Clinical Pharmacology and Therapeutics. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Research Mason, Jay W. Chugh, Rakesh Patel, Anasuya Gutte, Ranjeet Bhatia, Ashima Electrocardiographic Effects of a Supratherapeutic Dose of WCK 2349, a Benzoquinolizine Fluoroquinolone |
title | Electrocardiographic Effects of a Supratherapeutic Dose of WCK 2349, a Benzoquinolizine Fluoroquinolone |
title_full | Electrocardiographic Effects of a Supratherapeutic Dose of WCK 2349, a Benzoquinolizine Fluoroquinolone |
title_fullStr | Electrocardiographic Effects of a Supratherapeutic Dose of WCK 2349, a Benzoquinolizine Fluoroquinolone |
title_full_unstemmed | Electrocardiographic Effects of a Supratherapeutic Dose of WCK 2349, a Benzoquinolizine Fluoroquinolone |
title_short | Electrocardiographic Effects of a Supratherapeutic Dose of WCK 2349, a Benzoquinolizine Fluoroquinolone |
title_sort | electrocardiographic effects of a supratherapeutic dose of wck 2349, a benzoquinolizine fluoroquinolone |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6342240/ https://www.ncbi.nlm.nih.gov/pubmed/30369076 http://dx.doi.org/10.1111/cts.12594 |
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