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Purity: ≥98%
Landiolol (also known as LDLL600 and ONO 1101) is a beta1 selective, ultra-short-acting β1-adrenergic blocker which is useful for managing supraventricular tachyarrhythmias in sepsis. The medication landiolol functions as an extremely short-acting, highly cardioselective beta blocker. It functions as an anti-arrhythmic medication. Landiolol reduces hemodynamic responses to bronchoscopy-assisted suctioning in intubated ICU patients.
On November 22, 2024, The FDA approved landiolol for use in hospital critical care settings for the treatment of supraventricular tachycardia (atrial fibrillation and atrial flutter). The approval is based on clinical studies that demonstrate the management of heart rate with minimal reductions to blood pressure. “Rapiblyk approval in the US represents an important milestone for patients experiencing supraventricular tachycardia, including atrial fibrillation and atrial flutter, who need rapid and short-term heart rate reduction. After being available in Europe, we are delighted that this therapeutic option can be now available also for US patients,” said Martin Steinhart, CEO of AOP Health, in a news release.| Targets |
beta-adrenergic receptor
β1-adrenoceptor (ultra-short-acting, high β1-selectivity with β1/β2 selectivity ratio = 255). [2] |
|---|---|
| ln Vivo |
Mean age and Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores were similar between the 2 groups. Paroxysmal atrial fibrillation/flutter (87%), paroxysmal atrial tachycardia (10%), and paroxysmal supraventricular tachycardia (3%) were observed. The initial landiolol dose administered was 6.3 ± 5.8 g/kg per minute. Rapid and substantial reduction of heart rate was observed in the landiolol group without any deterioration of hemodynamics. Landiolol significantly reduced heart rate (from 145 ± 14 bpm to 90 ± 20 bpm) compared to the control group (from 136 ± 21 bpm to 109 ± 18 bpm, P < 0.05). The conversion to sinus rhythm was observed more frequently in the landiolol group than in the control group at every point (P < 0.01 at 8 h; P < 0.05 at 1 and 24 h).
Conclusion: Landiolol safely reduced heart rate and, in part, converted to sinus rhythm in septic patients with supraventricular tachyarrhythmias.[2] In a clinical study of 61 septic patients with supraventricular tachyarrhythmias (HR ≥ 120 bpm for >1 h), administration of Landiolol HCl (initial dose 6.3 ± 5.8 µg/kg/min by continuous intravenous infusion) rapidly and significantly reduced heart rate without deteriorating hemodynamics. Heart rate decreased from 145 ± 14 bpm to 119 ± 28 bpm at 1 hour and to 90 ± 20 bpm at 24 hours after initiation, compared to a lesser reduction in the control group (from 136 ± 21 bpm to 109 ± 18 bpm at 24 hours). [2] Landiolol HCl significantly promoted conversion to sinus rhythm. The conversion rates in the landiolol group were 25.6% at 1 hour, 55.3% at 8 hours, and 69.7% at 24 hours, compared to 0%, 18.2%, and 36.4% respectively in the control group. [2] Administration of Landiolol HCl did not significantly reduce arterial blood pressure or cardiac index in septic patients, indicating a favorable hemodynamic profile despite heart rate reduction. [2] |
| Animal Protocol |
Objectives: To elucidate pharmacokinetics and pharmacodynamics of landiolol hydrochloride, newer developed ultra-short-acting beta-blocker, in patients with various cardiac tachyarrhythmias.
Background: The short duration of action and titratability of landiolol hydrochloride make it ideal for use in patients with a clinical need for beta-blockers. Methods: In a total of 31 examinations we infused the drug in 19 patients (mean age, 55 +/- 14 years). After the persistence of the tachyarrhythmias was confirmed, continuous infusion was started at rates of 0.005, 0.01, 0.02, 0.04, and 0.08 mg/kg/min for 5 minutes (for paroxysmal atrial fibrillation, paroxysmal supraventricular tachycardia, and ventricular tachycardia) or 15 minutes (for ventricular premature complex). We analyzed the pharmacokinetics of 16 examinations. A one-compartment model provided a close fit for each blood concentration-time curve. [1] Aim: To investigate whether landiolol, an ultra-short-acting β1-antagonist, can safely and effectively control heart rate in septic patients with supraventricular tachyarrhythmias. Methods: We reviewed all patients with sepsis who admitted to our intensive care unit between January 2006 and December 2011. Sixty one septic patients suffered from supraventricular tachyarrhythmias (heart rate ≥ 120 bpm for > 1 h). Among 61 patients, 39 patients were treated with landiolol (landiolol group) and 22 patients were not treated with landiolol (control group). Arterial pressure, heart rate, cardiac rhythm, pulmonary arterial pressure and cardiac output (if a pulmonary arterial catheter was inserted) were compared between the 2 groups at 1, 8 and 24 h after the initiation of tachyarrhythmias.[2] |
| ADME/Pharmacokinetics |
The maximum plasma concentrations obtained clearly showed dose dependence and revealed a very short half-life (ranging from 2.3 to 4.0 minutes). The area under the plasma concentration-time curve also increased accordingly, indicating that it was dose-dependent. In patients with paroxysmal atrial fibrillation, landiolol hydrochloride reduced the heart rate from 111 ± 20 beats/min to 90 ± 10 beats/min. In 3 out of 5 patients with paroxysmal supraventricular tachycardia and 1 patient with ventricular tachycardia, sinus rhythm was restored without any adverse reactions. No significant changes were observed in peripheral blood pressure. Conclusion: The elimination half-life of landiolol hydrochloride is shorter than that of any other β-blocker and it is safe for use in the treatment of patients with various arrhythmias. [1]
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| Toxicity/Toxicokinetics |
164457 Canine LDLo, intravenously administered at 100 mg/kg: Behavioral effects: ataxia; Lung, pleural, or respiratory effects: dyspnea; Kidney, ureter, and bladder effects: other changes. Journal of Toxicological Science, 22(Supplement)
164457 Rat LDLo, intravenously administered at 150 mg/kg: Behavioral effects: altered sleep duration (including altered righting reflex); Behavioral effects: tremor; Lung, pleural, or respiratory effects: respiratory depression. Journal of Toxicological Science, 22(Supplement) |
| References |
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| Additional Infomation |
Landilol hydrochloride belongs to the morpholine class of drugs.
See also: Landilol (note moved to). Drug indications Treatment of supraventricular arrhythmias Landilol hydrochloride is an ultra-short-acting, highly selective β1-adrenergic receptor antagonist used to control heart rate and restore sinus rhythm in supraventricular tachycardia. [2] In patients with sepsis, it effectively reduces heart rate and promotes the restoration of sinus rhythm without causing hypotension or hemodynamic deterioration, and is therefore suitable for critically ill patients with hemodynamic instability. [2] In this study of patients with sepsis, the typical initial dose was 6.3 ± 5.8 µg/kg/min, administered by continuous intravenous infusion. [2] The product is marketed in Japan as ONOACT (Ono Pharmaceutical Co., Ltd., Osaka, Japan). [2] |
| Molecular Formula |
C25H40CLN3O8
|
|---|---|
| Molecular Weight |
546.0534
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| Exact Mass |
545.25
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| Elemental Analysis |
C, 54.99; H, 7.38; Cl, 6.49; N, 7.70; O, 23.44
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| CAS # |
144481-98-1
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| Related CAS # |
133242-30-5; 144481-98-1 (HCl)
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| PubChem CID |
164457
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| Appearance |
White to off-white solid powder
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| Density |
1.201g/cm3
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| Boiling Point |
727.5ºC at 760mmHg
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| Melting Point |
122-127ºC
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| Flash Point |
393.8ºC
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| Vapour Pressure |
3.24E-22mmHg at 25°C
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| LogP |
2.377
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
14
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| Heavy Atom Count |
37
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| Complexity |
666
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| Defined Atom Stereocenter Count |
2
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| SMILES |
Cl[H].O1[C@]([H])(C([H])([H])OC(C([H])([H])C([H])([H])C2C([H])=C([H])C(=C([H])C=2[H])OC([H])([H])[C@]([H])(C([H])([H])N([H])C([H])([H])C([H])([H])N([H])C(N2C([H])([H])C([H])([H])OC([H])([H])C2([H])[H])=O)O[H])=O)C([H])([H])OC1(C([H])([H])[H])C([H])([H])[H]
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| InChi Key |
DLPGJHSONYLBKP-IKGOIYPNSA-N
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| InChi Code |
InChI=1S/C25H39N3O8.ClH/c1-25(2)35-18-22(36-25)17-34-23(30)8-5-19-3-6-21(7-4-19)33-16-20(29)15-26-9-10-27-24(31)28-11-13-32-14-12-28;/h3-4,6-7,20,22,26,29H,5,8-18H2,1-2H3,(H,27,31);1H/t20-,22+;/m0./s1
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| Chemical Name |
[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl 3-[4-[(2S)-2-hydroxy-3-[2-(morpholine-4-carbonylamino)ethylamino]propoxy]phenyl]propanoate;hydrochloride
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| Synonyms |
ONO1101; ONO-1101; ONO 1101 hydrochloride; LDLL600; LDLL 600; LDLL-600; Landiolol; Landiolol HCl; Landiolol hydrochloride
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: 100~250 mg/mL (183.1~457.8 mM)
Water: ~100 mg/mL Ethanol: ~42 mg/mL |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (3.81 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 (3.81 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 (3.81 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8313 mL | 9.1567 mL | 18.3133 mL | |
| 5 mM | 0.3663 mL | 1.8313 mL | 3.6627 mL | |
| 10 mM | 0.1831 mL | 0.9157 mL | 1.8313 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT05084118 | Recruiting | Drug: Landiolol HCl Drug: Placebo |
Postoperative Complications Atrial Fibrillation |
Medical University of Vienna | October 21, 2021 | Phase 3 |
| NCT03779178 | Completed | Drug: Landiolol Drug: Placebo |
Atrial Fibrillation | Hospices Civils de Lyon | January 17, 2019 | Phase 3 |
| NCT00311038 | Completed | Drug: ONO-1101 | Coronary Artery Disease | Ono Pharmaceutical Co. Ltd | April 2006 | Phase 2 |
| NCT00212680 | Completed | Drug: ONO-1101 | Postoperative Supraventricular Tachyarrythmia |
Ono Pharma USA Inc | April 2006 | Phase 2 |
| NCT00212654 | Completed | Drug: ONO-1101 | Postoperative Supraventricular Tachyarrythmia |
Ono Pharmaceutical Co. Ltd | June 2001 | Phase 2 Phase 3 |
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