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Model-Informed Development of Sotalol Loading and Dose Escalation Employing an Intravenous Infusion
BACKGROUND: Sotalol is often employed to prevent recurrence of symptomatic atrial flutter/atrial fibrillation. Because sotalol can prolong the QT interval excessively causing ventricular arrhythmias, a 3-day in-hospital loading or dose escalation period is mandated with oral administration in the pr...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elmer Press
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7430892/ https://www.ncbi.nlm.nih.gov/pubmed/32849964 http://dx.doi.org/10.14740/cr1143 |
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author | Somberg, John C. Vinks, Alexander A. Dong, Min Molnar, Janos |
author_facet | Somberg, John C. Vinks, Alexander A. Dong, Min Molnar, Janos |
author_sort | Somberg, John C. |
collection | PubMed |
description | BACKGROUND: Sotalol is often employed to prevent recurrence of symptomatic atrial flutter/atrial fibrillation. Because sotalol can prolong the QT interval excessively causing ventricular arrhythmias, a 3-day in-hospital loading or dose escalation period is mandated with oral administration in the product label for patient safety. In patients with normal renal function, 3 days (five oral doses) are required to obtain steady state maximum sotalol concentration, which results in maximum QT prolongation. The aim of this study is to develop an intravenous to oral loading regime for sotalol therapy that reduces the 3-day in-hospital initiation or dose escalation with oral administration to 1 day without compromising patient safety. METHODS: Using model-informed drug development techniques, simulations were developed for initiation and dose escalation of sotalol therapy by employing an intravenous loading dose followed by oral sotalol administrations. RESULTS: In patients with normal renal function, an initial 1-h loading dose of intravenous sotalol followed by two oral doses in 24 h has been developed permitting attainment of three maximum serum concentrations reflecting maximum QT prolongation in a 1-day observation period. Dosing regimens for patients with impaired renal function are also developed. CONCLUSIONS: In patients with normal renal function, using an intravenous loading dose followed by oral administrations permits safe initiation or dose escalation of sotalol in 1 day instead of the 3-day dosing regimen with oral administration. |
format | Online Article Text |
id | pubmed-7430892 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Elmer Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-74308922020-08-25 Model-Informed Development of Sotalol Loading and Dose Escalation Employing an Intravenous Infusion Somberg, John C. Vinks, Alexander A. Dong, Min Molnar, Janos Cardiol Res Original Article BACKGROUND: Sotalol is often employed to prevent recurrence of symptomatic atrial flutter/atrial fibrillation. Because sotalol can prolong the QT interval excessively causing ventricular arrhythmias, a 3-day in-hospital loading or dose escalation period is mandated with oral administration in the product label for patient safety. In patients with normal renal function, 3 days (five oral doses) are required to obtain steady state maximum sotalol concentration, which results in maximum QT prolongation. The aim of this study is to develop an intravenous to oral loading regime for sotalol therapy that reduces the 3-day in-hospital initiation or dose escalation with oral administration to 1 day without compromising patient safety. METHODS: Using model-informed drug development techniques, simulations were developed for initiation and dose escalation of sotalol therapy by employing an intravenous loading dose followed by oral sotalol administrations. RESULTS: In patients with normal renal function, an initial 1-h loading dose of intravenous sotalol followed by two oral doses in 24 h has been developed permitting attainment of three maximum serum concentrations reflecting maximum QT prolongation in a 1-day observation period. Dosing regimens for patients with impaired renal function are also developed. CONCLUSIONS: In patients with normal renal function, using an intravenous loading dose followed by oral administrations permits safe initiation or dose escalation of sotalol in 1 day instead of the 3-day dosing regimen with oral administration. Elmer Press 2020-10 2020-08-07 /pmc/articles/PMC7430892/ /pubmed/32849964 http://dx.doi.org/10.14740/cr1143 Text en Copyright 2020, Somberg et al. http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution Non-Commercial 4.0 International License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Article Somberg, John C. Vinks, Alexander A. Dong, Min Molnar, Janos Model-Informed Development of Sotalol Loading and Dose Escalation Employing an Intravenous Infusion |
title | Model-Informed Development of Sotalol Loading and Dose Escalation Employing an Intravenous Infusion |
title_full | Model-Informed Development of Sotalol Loading and Dose Escalation Employing an Intravenous Infusion |
title_fullStr | Model-Informed Development of Sotalol Loading and Dose Escalation Employing an Intravenous Infusion |
title_full_unstemmed | Model-Informed Development of Sotalol Loading and Dose Escalation Employing an Intravenous Infusion |
title_short | Model-Informed Development of Sotalol Loading and Dose Escalation Employing an Intravenous Infusion |
title_sort | model-informed development of sotalol loading and dose escalation employing an intravenous infusion |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7430892/ https://www.ncbi.nlm.nih.gov/pubmed/32849964 http://dx.doi.org/10.14740/cr1143 |
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