Täubel, J; Ferber, G; Fox, G; Fernandes, S; Lorch, U; Camm, AJ
(2017)
Thorough QT study of the effect of intravenous amisulpride on QTc interval in Caucasian and Japanese healthy subjects.
Br J Clin Pharmacol, 83 (2).
pp. 339-348.
ISSN 1365-2125
https://doi.org/10.1111/bcp.13128
SGUL Authors: Camm, Alan John
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Abstract
AIM: The D2 /D3 antagonist amisulpride has shown promising efficacy against postoperative nausea and vomiting (PONV) at low doses. We investigated whether intravenous amisulpride has an effect on the QTc interval in a formal Thorough QT study (TQT). METHODS: This was a randomized, double-blind, placebo and positive-controlled, four-way crossover study. Forty healthy Caucasian and Japanese subjects were included to receive a single administration of 5 mg and 40 mg of i.v. amisulpride or a single oral dose of moxifloxacin or placebo per period. RESULTS: The therapeutic dose of 5 mg amisulpride was associated with a slight, transient increase in mean ΔΔQTcF, from 2.0 ms prior to dosing to a peak of 5 ms (90% CI: 2.8, 7.1 ms) at 8 min, decreasing to 2.1 ms at 30 min after dosing. The supra-therapeutic dose of 40 mg given at twice the infusion rate was associated with prolongation in ΔΔQTcF peaking at 23.4 ms (90% CI: 21.3, 25.5 ms) at the end of infusion (8 min), returning below 10 ms within 1.5 h. Assay sensitivity was confirmed; ΔΔQTcF had increased by 12.3 ms (90% CI 10.1, 14.6 ms) at 4 h post-dose. The PK-PD relationship revealed no differences between Caucasian and Japanese subjects (p-value > 0.5). CONCLUSIONS: Amisulpride has a plasma concentration-dependent effect on the QTc interval. The proposed therapeutic dose for management of PONV does not lead to a prolongation of QTcF above the threshold of regulatory concern, while such effect could not be excluded for the supratherapeutic dose.
Item Type: | Article | ||||||||
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Additional Information: | © 2016 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society. DOI:10.1111/bcp.13128 This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. | ||||||||
Keywords: | QTc interval, Thorough QT study, amisulpride, Pharmacology & Pharmacy, 1115 Pharmacology And Pharmaceutical Sciences | ||||||||
SGUL Research Institute / Research Centre: | Academic Structure > Molecular and Clinical Sciences Research Institute (MCS) Academic Structure > Molecular and Clinical Sciences Research Institute (MCS) > Cardiac (INCCCA) |
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Journal or Publication Title: | Br J Clin Pharmacol | ||||||||
ISSN: | 1365-2125 | ||||||||
Language: | eng | ||||||||
Dates: |
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Publisher License: | Publisher's own licence | ||||||||
PubMed ID: | 27618796 | ||||||||
Go to PubMed abstract | |||||||||
URI: | https://openaccess.sgul.ac.uk/id/eprint/108271 | ||||||||
Publisher's version: | https://doi.org/10.1111/bcp.13128 |
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