Hydroquinidine is a class Ia antiarrhythmic drug. The study mentions it inhibits the transient outward potassium current (I_to) of the cardiac action potential, which is implicated in Brugada syndrome. [2]

This clinical study demonstrates the in vivo (human) efficacy of long-term Hydroquinidine treatment in patients with Short QT Syndrome (SQTS). In 17 treated patients, Hydroquinidine (mean dose 584 ± 53 mg/day) significantly prolonged the QTc interval from a baseline of 331 ± 3 ms to 391 ± 5 ms (mean prolongation 60 ± 6 ms; p < 0.001).
In a matched-period analysis of 15 patients treated long-term (mean 6 ± 1 years), the percentage of patients experiencing life-threatening arrhythmic events (LAE: cardiac arrest or sudden cardiac death) dropped from 40% in an equal period before treatment to 0% during treatment (p = 0.03). The number of LAE per patient dropped from 0.73 ± 0.30 to 0 (p = 0.026).
In a separate analysis of 16 SQTS patients who had survived a prior cardiac arrest, the annual rate of LAE dropped from 12% (10 events over 82 person-years) off treatment to 0% (0 events over 44 person-years) on Hydroquinidine treatment (p = 0.028). [1]
This clinical study (human) evaluated the efficacy of Hydroquinidine in patients with Brugada syndrome (BrS).
In asymptomatic BrS patients with inducible ventricular tachycardia/ventricular fibrillation (VT/VF) undergoing electrophysiologic (EP)-guided therapy (n=29), Hydroquinidine (mean dose 609 ± 89 mg/day) prevented VT/VF inducibility in 22 patients (76%). [2]
Among 21 asymptomatic, inducible patients who received long-term Hydroquinidine therapy (mean follow-up 17 ± 13 months), 17 (81%) remained asymptomatic. Two patients experienced syncope during follow-up; one case was associated with major QTc prolongation (530 ms) and documented non-sustained VT runs, while the other was unexplained but possibly linked to non-compliance. Two other patients discontinued Hydroquinidine due to late gastrointestinal intolerance. [2]
In a separate group of 10 asymptomatic, inducible patients who received an implantable cardioverter-defibrillator (ICD) instead of long-term Hydroquinidine (due to persistent inducibility or early intolerance), one appropriate ICD shock occurred during a mean follow-up of 13 ± 8 months. [2]
In four symptomatic BrS patients with a history of multiple appropriate ICD shocks, long-term Hydroquinidine therapy prevented shock recurrence and VT/VF episodes in all cases during a mean follow-up of 14 ± 8 months. A dramatic reduction in ventricular arrhythmia salvos was documented in one patient. [2]

The study monitored plasma concentrations of quinidine. The mean plasma concentration in treated patients was 2.7 ± 3.3 µmol/L. The usual therapeutic concentration range (measured by fluorescence) was 3 to 6 µmol/L. The dose was adjusted based on plasma concentrations and electrophysiological findings. The standard dose was 300 mg twice daily (600 mg/day) in a sustained-release formulation. If ventricular tachycardia/fibrillation was still induced and the plasma concentration was below 3 µmol/L, the dose was increased to 900 mg/day. [2]

In this study, hydroquinidine treatment was generally well tolerated. Two of the 17 patients (12%) discontinued treatment within one week due to gastrointestinal intolerance (diarrhea). No arrhythmic events were observed during treatment. The study noted that it was better tolerated than a previous study on Brugada syndrome, which may be due to the lower mean daily dose in this study (584 ± 53 mg/day vs. 738 ± 25 mg/day). [1] During the trial, seven of the 35 patients (20%) experienced drug intolerance, mainly manifested as diarrhea, and two of them discontinued hydroquinidine as a result. One patient discontinued treatment after one week of treatment due to reversible hydroquinidine-induced hepatitis (3-fold increase in transaminases), accompanied by nausea and fatigue. [2]
One patient experienced syncope one month after starting hydroquinidine, accompanied by a significantly prolonged QTc interval to 530 ms (baseline value 425 ms), and episodes of monomorphic ventricular tachycardia were recorded. This was considered a possible arrhythmogenic event. QTc interval >500 ms was observed only in this patient. [2]
Overall, 5 out of 35 patients (14%) discontinued hydroquinidine due to extracardiac side effects (gastrointestinal intolerance or hepatitis). [2]

[1]. Hydroquinidine Prevents Life-Threatening Arrhythmic Events in Patients With Short QT Syndrome. J Am Coll Cardiol. 2017 Dec 19;70(24):3010-3015.

[2]. Hydroquinidine therapy in Brugada syndrome. J Am Coll Cardiol. 2004 May 19;43(10):1853-60.

[3]. Comparison of the effectiveness of dihydroquinidine and quinidine on ventricular ectopy after acute and chronic administration. Cardiovasc Drugs Ther. 1988 Dec;2(5):679-86.

Hydroquinidine quinidine is being investigated in the clinical trial NCT00927732 (comparison of Hydroquinidine quinidine with placebo in patients with Brugada syndrome). See also: Hydroquinidine Quinine (note moved here). Hydroquinidine quinidine is a quinidine derivative currently used to treat short QT syndrome (SQTS), a rare inherited arrhythmia characterized by an abnormally shortened QT interval on an electrocardiogram and a high risk of sudden death. The study protocol involved starting Hydroquinidine quinidine at a dose of 3 mg/kg/day and gradually increasing the dose until the QTc interval was >360 ms. The mean maintenance dose was 584 ± 53 mg/day (approximately 8 mg/kg/day). The study concluded that long-term use of Hydroquinidine quinidine effectively prolongs the QT interval and prevents life-threatening arrhythmic events in high-risk patients with short QT syndrome (SQTS). Studies have shown that this drug can be used as adjunctive therapy to reduce the number of discharges from implantable cardioverter defibrillators (ICDs), or as an alternative therapy when ICDs are contraindicated, unavailable, or refused by the patient.
The authors advocate for the continued availability of quinidines worldwide for the treatment of life-threatening inherited arrhythmias, such as SQTS. [1]
This study used hydroquinidine hydrochloride (extended-release formulation) to treat Brugada syndrome (BrS). [2] The likely mechanism of Brugada syndrome (BrS) is the suppression of transient outward potassium currents (I_to), thereby rebalancing the current of phase 1 epicardial action potentials and reducing the matrix of phase 2 reentrant arrhythmias. [2] The treatment regimen included an initial electrophysiological study. Hydroquinidine was then started and repeated after at least two weeks to assess the suppression of ventricular tachycardia/ventricular fibrillation evoked by the drug. Long-term treatment was continued if the patient was unable to induce ventricular tachycardia/ventricular fibrillation and tolerated the drug. [2] ECG changes observed after quinidine treatment included slight but significant prolongation of QRS duration (13 ± 12 ms) and QTc interval (10 ± 7 ms). In 12 of the 35 patients (34%), characteristic Brugada-type ST-segment elevation was reduced or returned to normal, but this was not associated with prevention of ventricular tachycardia/ventricular fibrillation induced by quinidine. [2] This study suggests that quinidine may be an alternative prophylactic treatment to ICD implantation for some asymptomatic BrS patients who may develop arrhythmias, but emphasizes the need for close monitoring of QTc interval and plasma drug concentration to assess patient tolerability and compliance. [2]

C20H26N2O2

326.4326

326.199

1435-55-8

1476-98-8 (mono-hydrochloride);1668-97-9 (mono-hydrochloride)

91503

White to off-white solid powder

1.2±0.1 g/cm3

498.4±30.0 °C at 760 mmHg

169-170 ºC

255.2±24.6 °C

0.0±1.3 mmHg at 25°C

1.626

3.77

1

4

4

24

432

4

CC[C@H]1CN2CC[C@H]1C[C@@H]2[C@H](C3=C4C=C(C=CC4=NC=C3)OC)O

LJOQGZACKSYWCH-LHHVKLHASA-N

InChI=1S/C20H26N2O2/c1-3-13-12-22-9-7-14(13)10-19(22)20(23)16-6-8-21-18-5-4-15(24-2)11-17(16)18/h4-6,8,11,13-14,19-20,23H,3,7,9-10,12H2,1-2H3/t13-,14-,19+,20-/m0/s1

(S)-[(2R,4S,5R)-5-ethyl-1-azabicyclo[2.2.2]octan-2-yl]-(6-methoxyquinolin-4-yl)methanol

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: (1). This product requires protection from light (avoid light exposure) during transportation and storage.  (2). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~20.83 mg/mL (~63.81 mM)

Solubility in Formulation 1: ≥ 2.08 mg/mL (6.37 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

---

Solubility in Formulation 2: ≥ 2.08 mg/mL (6.37 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

---

View More

Solubility in Formulation 3: ≥ 2.08 mg/mL (6.37 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

---

 (Please use freshly prepared in vivo formulations for optimal results.)