Landiolol

Structural formula
General
Non-proprietary name	Landiolol
other names	4 - [(2 S ) -2-Hydroxy-3 - {[2 - [(4-morpholinylcarbonyl) amino] ethyl} amino] propoxy] -benzenopropanoic acid [(4 S ) -2,2-dimethyl-1,3- dioxolan-4-yl] methyl ester; 4- [2-Hydroxy-3 - [{2 - [(4-morpholinylcarbonyl) amino} ethyl] amino] propoxy] benzene propanoic acid [ S - ( R , R )] - (2,2-dimethyl-1, 3-dioxolan-4-yl) methyl ester;
Molecular formula	C 25 H 39 N 3 O 8
Brief description	white solid (hydrochloride)
External identifiers / databases
PubChem	114905
ChemSpider	102855
DrugBank	DB12212
Wikidata	Q6484656
Drug information
ATC code	C07 AB14
Drug class	Sympatholytics
Mechanism of action	β-receptor blockers
properties
Molar mass	546.05 g mol −1
Physical state	firmly
solubility	soluble in water (hydrochloride)
safety instructions
	Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances Hydrochloride; Caution
H and P phrases	H: 315-319
	P: 305 + 351 + 338
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Landiolol is a drug from the group of β ₁ -blockers that is used for the acute treatment of a too fast ( tachycardia ) or irregular heartbeat during or after an operation, or in other situations in which it is necessary to control the heartbeat.

pharmacology

Landiolol is ultra-short and highly cardioselectively effective; it is administered intravenously and its effect can be easily controlled. The cardioselectivity is 7 to 8 times higher than that of the similar active ingredient Esmolol .

The plasma half-life of Landiolol is about 4 minutes, the onset of action occurs within 1 minute, i.e. even faster than with Esmolol. Landiolol is rapidly hydrolyzed , on the one hand by the carboxylesterase in the liver and on the other hand by the pseudocholinesterase in the plasma. 99% of the dose is eliminated from the urine within 24 hours, primarily as inactive metabolites .

Tabular comparison of iv administered β-blockers:

Surname	Max. Half-life (min)	Cardioselectivity (β ₁ / β ₂ )	Metabolism
Landiolol	4th	250	Pseudocholinesterase
Esmolol	9	30th	Ery esterase
Metoprolol	420	3	CYP2D6 (liver)

The recommended dose is 10–40 µg / kg / min up to a maximum of 80 µg / kg / min, a 1-minute bolus dose of 100 µg / kg is possible. In clinical practice, especially in cardiac surgery patients, an average lower dose of less than 10 µg / kg / min is also useful.

The dose-response relationship of landiolol in the therapeutic dose range is linear.

application areas

Landiolol has been approved in Japan since 2013 and in some European countries since 2016 for the treatment of intra- and postoperative tachyarrhythmias ( supraventricular tachycardia , atrial fibrillation , atrial flutter, non-compensatory sinus tachycardia ). In clinical practice, Landiolol has also proven to be effective in the prevention of postoperative tachyarrhythmias such as atrial fibrillation after coronary artery bypass operations .

In patients with restricted left ventricular function (LVEF <40%, CI <2.5 l / min / m², NYHA class 3-4) e.g. B. after heart operations, in ischemia or in septic conditions, lower doses of landiolol were used for treatment to control the heart rate.

Extraction and presentation

Landiolol can be obtained by reacting ( S ) - (2,2-dimethyl-1,3-dioxolan-4-yl) methyl-3- (4-hydroxyphenyl) propanoate with epichlorohydrin and 2- (morpholine-4-carboxamido) ethanamine become.

Finished medicinal products

Onoact ( J ), Rapibloc (D, A, HR )

Web links

Landiolol (Rapibloc®) drug profile in the Pharmazeutische Zeitung

Individual evidence

↑ ^a ^b ^c ^d ^e data sheet Landiolol hydrochloride, ≥98% (HPLC) from Sigma-Aldrich , accessed on September 30, 2017 ( PDF ).
↑ Plosker GL et al .: Landiolol: A Review of its use in Intraoperative and Postoperative Tachyarrhythmias . In: Drugs . tape 73 , no. 9 . Adis, 2013, p. 959-977 , doi : 10.1007 / s40265-013-0077-4 .
↑ Nasrollahi-Shirazi S et al .: Comparison of the β- Adrenergic Receptor Antagonists Landiolol and Esmolol: Receptor Selectivity, Partial Agonism, and Pharmacochaperoning Actions . In: J Pharmacol Exp Ther . tape 359 , no. 1 , 2016, p. 73-81 .
↑ Krumpl G et al .: Bolus application of landiolol and esmolol: comparison of the pharmacokinetic and pharmacodynamic profiles in a healthy Caucasion group . In: Eur J Clin Pharmacol . tape 73 , 2017, p. 417-428 .
↑ Li L et al .: Efficacy and safety of landiolol for prevention of atrial fibrillation after cardiac surgery: a meta-analysis of randomized controlled trials . In: Int J Clin Exp Med . tape 8 , no. 7 , 2015, p. 10265-10273 .
↑ Google patent search: Patent EP2687521A1 - "Process for the enantioselective synthesis of landiolol" - Google patent search , accessed September 30, 2017.

[Sigma-1] ↑ ^a ^b ^c ^d ^e data sheet Landiolol hydrochloride, ≥98% (HPLC) from Sigma-Aldrich , accessed on September 30, 2017 ( PDF ).

[2] Plosker GL et al .: Landiolol: A Review of its use in Intraoperative and Postoperative Tachyarrhythmias . In: Drugs . tape 73 , no. 9 . Adis, 2013, p. 959-977 , doi : 10.1007 / s40265-013-0077-4 .

[3] Nasrollahi-Shirazi S et al .: Comparison of the β- Adrenergic Receptor Antagonists Landiolol and Esmolol: Receptor Selectivity, Partial Agonism, and Pharmacochaperoning Actions . In: J Pharmacol Exp Ther . tape 359 , no. 1 , 2016, p. 73-81 .

[4] Krumpl G et al .: Bolus application of landiolol and esmolol: comparison of the pharmacokinetic and pharmacodynamic profiles in a healthy Caucasion group . In: Eur J Clin Pharmacol . tape 73 , 2017, p. 417-428 .

[5] Li L et al .: Efficacy and safety of landiolol for prevention of atrial fibrillation after cardiac surgery: a meta-analysis of randomized controlled trials . In: Int J Clin Exp Med . tape 8 , no. 7 , 2015, p. 10265-10273 .

[Google_Patentsuche-6] Google patent search: Patent EP2687521A1 - "Process for the enantioselective synthesis of landiolol" - Google patent search , accessed September 30, 2017.