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Steroidal hormones for the treatment and prevention of torsades de pointes

A ventricular tachycardia, androgen technology, used in the field of cardiology, can solve problems such as changes in the type of contraceptives that have not been proven QTc

Active Publication Date: 2019-01-04
ASSISTANCE PUBLIQUE HOPITAUX DE PARIS +2
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Furthermore, by comparison, Sedlak et al. did not have a group of patients taking drugs containing gestodene
[0035] It should also be noted that in the case of co-treatment no differences between QTc lengths have been demonstrated as a function of contraceptive type (Table 5 and Discussion)

Method used

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  • Steroidal hormones for the treatment and prevention of torsades de pointes
  • Steroidal hormones for the treatment and prevention of torsades de pointes
  • Steroidal hormones for the treatment and prevention of torsades de pointes

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0143] Example 1 - Development of Markers Representing IKr Potassium Channel Inhibition

[0144] The results obtained in a cohort of 995 healthy volunteers (18 to 60 years of age, European or North African ancestry) were used to develop markers representative of IKr potassium channel inhibition.

[0145] Results were obtained in one exploration cohort (cohorte d'exploration) to identify the markers described below, and a replicate cohort (cohorte de réplication) was used to validate the results obtained in the exploration cohort.

[0146] Briefly, patients' electrocardiograms (ECGs) were recorded (each in triplicate for 10 s) after a 10-min supine rest. The patient was then given a single oral dose of 80 mg sotalol and continued ECG monitoring. Three hours after sotalol administration, the ECG was recorded again (in triplicate) after the subject lay supine for 10 minutes.

[0147] ECG analysis

[0148] The QT prolongation by sotalol represents an equivalent form of the ...

Embodiment 2

[0189] Example 2 - Levonorgestrel and desogestrel have comparable protective effects on the inhibition of IKr potassium channels

[0190] crowd

[0191] The study was performed on 615 healthy females of European or North African type, aged between 18 and 60 years, with QTcF <450ms, no known disease or chronic or chronic treatment, except contraception, without any congenital long QT syndrome, A family history of cardiac arrhythmias or sudden death.

[0192] Measurement and calculation of various QTcF, TAmp and TpTe data

[0193]According to the same protocol as in Example 1, QTcF, TAmp and TpTe were measured before and 3 hours after administration of a single 80 mg oral dose of sotalol.

[0194] ΔQTcF, ΔTpTe and ΔTAmp were also calculated.

[0195] principal component analysis

[0196] Principal component analysis (XLStat software, ) to generate three new decorrelated values ​​PC1, PC2 and PC3.

[0197] result

[0198] The PC1 variant thus obtained, in which ...

Embodiment 3

[0216] Example 3 - Treatment of Torsades de Pointes by Administration of Testosterone

[0217] In men with ischemic heart disease and Erdheim-Chester disease with arrhythmic storm, Torsades de pointes with long QT and notch (double peak (gap) of the T wave), found Peripheral hypogonadism in which torsades de pointes is iatrogenic and facilitated by bradycardia, with more than 7 episodes in less than a week.

[0218] Administer testosterone to the patient ( Testosterone enanthate 250 mg / ml), in an amount such that testosterone levels could be maintained so that his hypogonadism could be corrected, bradycardia corrected, and an implantable defibrillator implanted as secondary prevention.

[0219] Following testosterone introduction, circulating concentrations of bioavailable testosterone and its repolarization become normalized.

[0220] Three months after the introduction of testosterone, monitoring of the defibrillator confirmed no recurrence of torsades de pointes despit...

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Abstract

The invention relates to a new method for the prevention and treatment of torsades de pointes by administering a gestagen having an androgenic effect.

Description

technical field [0001] The present invention relates to the field of cardiology, and more particularly to a method for preventing or reducing the extent of repolarisation disorders and thus the occurrence of endogenous or exogenous facilitators or triggers (e.g. administration of a drug) A novel approach to the risk of torsades de pointes afterward. Background technique [0002] The term "torsades de pointes" refers to a specific type of ventricular tachycardia, which is an excessive arrhythmia of the ventricles that results in an accelerated heart rate, such as tachycardia (however distinct from ventricular fibrillation) . [0003] There are two types of torsades de pointes: torsades de pointes with a long QT interval, and polymorphic ventricular tachycardia with a normal borderline QT with a distorted appearance. [0004] The role of sex hormones in modulating QT or QTc, which is QT corrected relative to heart rate, has been intensively studied according to methods known...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/568A61K31/5685A61K31/56A61P9/00A61K31/57A61K31/565A61K31/567
CPCA61K31/568A61K31/565A61K31/567A61K31/5685A61K31/57A61P43/00A61P9/00A61P9/06A61K2300/00A61P9/12A61K9/0019A61K9/0053
Inventor J-E·塞勒姆C·丰克-布伦塔诺A·巴舍洛X·温特劳布
Owner ASSISTANCE PUBLIQUE HOPITAUX DE PARIS
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