Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C25H39N3O8 |
Molecular Weight | 509.5925 |
Optical Activity | ( - ) |
Defined Stereocenters | 2 / 2 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CC1(C)OC[C@@H](COC(=O)CCC2=CC=C(OC[C@@H](O)CNCCNC(=O)N3CCOCC3)C=C2)O1
InChI
InChIKey=WMDSZGFJQKSLLH-RBBKRZOGSA-N
InChI=1S/C25H39N3O8/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)/t20-,22+/m0/s1
Molecular Formula | C25H39N3O8 |
Molecular Weight | 509.5925 |
Charge | 0 |
Count |
|
Stereochemistry | ABSOLUTE |
Additional Stereochemistry | No |
Defined Stereocenters | 2 / 2 |
E/Z Centers | 0 |
Optical Activity | UNSPECIFIED |
DescriptionSources: http://www.ncbi.nlm.nih.gov/pubmed/23760735
Sources: http://www.ncbi.nlm.nih.gov/pubmed/23760735
Landiolol (Onoact) is an intravenously administered, ultra short-acting β1-blocker with an elimination half-life of 3-4 min and ≈8-fold greater cardioselectivity than esmolol in vitro. It is approved in Japan for the treatment of intraoperative and postoperative tachyarrhythmias, but in clinical practice is also used to prevent postoperative tachyarrhythmias, such as atrial fibrillation after coronary artery bypass grafting. Randomized controlled trials in patients undergoing open-heart surgery demonstrated that various dosages of landiolol (0.0005-0.04 mg/kg/min) [0.5-40 μg/kg/min] were more effective than diltiazem in converting postoperative atrial fibrillation to normal sinus rhythm during the first 8 h after surgery, and were more effective than placebo (or no landiolol) in preventing the development of atrial fibrillation during the first week after surgery (primary efficacy endpoints). Landiolol was generally well tolerated in clinical trials, with a relatively low risk of hypotension and bradycardia, although routine monitoring of cardiac function during landiolol administration is important. In general, adverse events such as reduced blood pressure resolve quickly after discontinuation of landiolol. Thus, as an ultra short-acting β1-blocker with a rapid onset of action and readily titratable and rapidly reversible effects, landiolol represents an important agent for the management of intraoperative and postoperative tachyarrhythmias.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL213 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22418070 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Unknown Approved UseUnknown |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
1.14 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27373605/ |
0.3 mg/kg single, intravenous dose: 0.3 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered: |
LANDIOLOL plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
0.79 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27373605/ |
0.2 mg/kg single, intravenous dose: 0.2 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered: |
LANDIOLOL plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
0.29 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27373605/ |
0.1 mg/kg single, intravenous dose: 0.1 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered: |
LANDIOLOL plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
0.1 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27373605/ |
0.3 mg/kg single, intravenous dose: 0.3 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered: |
LANDIOLOL plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
0.06 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27373605/ |
0.2 mg/kg single, intravenous dose: 0.2 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered: |
LANDIOLOL plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
0.03 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27373605/ |
0.1 mg/kg single, intravenous dose: 0.1 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered: |
LANDIOLOL plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
3.63 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27373605/ |
0.3 mg/kg single, intravenous dose: 0.3 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered: |
LANDIOLOL plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
3.43 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27373605/ |
0.2 mg/kg single, intravenous dose: 0.2 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered: |
LANDIOLOL plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
3.2 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27373605/ |
0.1 mg/kg single, intravenous dose: 0.1 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered: |
LANDIOLOL plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
90% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27373605/ |
0.3 mg/kg single, intravenous dose: 0.3 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered: |
LANDIOLOL plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
90% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27373605/ |
0.2 mg/kg single, intravenous dose: 0.2 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered: |
LANDIOLOL plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
90% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27373605/ |
0.1 mg/kg single, intravenous dose: 0.1 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered: |
LANDIOLOL plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
40 ug/kg/min single, intravenous Higher than recommended Dose: 40 ug/kg/min Route: intravenous Route: single Dose: 40 ug/kg/min Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
|
11.8 ug/kg/min single, intravenous Studied dose Dose: 11.8 ug/kg/min Route: intravenous Route: single Dose: 11.8 ug/kg/min Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
Other AEs: Hypotension, Bradycardia... Other AEs: Hypotension (20.7%) Sources: Bradycardia (3.4%) Heart failure (3.4%) Nausea (3.4%) Chest discomfort (3.4%) Liver function test increased (3.4%) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Hypotension | 20.7% | 11.8 ug/kg/min single, intravenous Studied dose Dose: 11.8 ug/kg/min Route: intravenous Route: single Dose: 11.8 ug/kg/min Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
Bradycardia | 3.4% | 11.8 ug/kg/min single, intravenous Studied dose Dose: 11.8 ug/kg/min Route: intravenous Route: single Dose: 11.8 ug/kg/min Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
Chest discomfort | 3.4% | 11.8 ug/kg/min single, intravenous Studied dose Dose: 11.8 ug/kg/min Route: intravenous Route: single Dose: 11.8 ug/kg/min Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
Heart failure | 3.4% | 11.8 ug/kg/min single, intravenous Studied dose Dose: 11.8 ug/kg/min Route: intravenous Route: single Dose: 11.8 ug/kg/min Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
Liver function test increased | 3.4% | 11.8 ug/kg/min single, intravenous Studied dose Dose: 11.8 ug/kg/min Route: intravenous Route: single Dose: 11.8 ug/kg/min Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
Nausea | 3.4% | 11.8 ug/kg/min single, intravenous Studied dose Dose: 11.8 ug/kg/min Route: intravenous Route: single Dose: 11.8 ug/kg/min Sources: |
unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
no | ||||
no | ||||
no | ||||
no | ||||
no |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://www.pmda.go.jp/PmdaSearch/iyakuDetail/ResultDataSetPDF/180188_2123404D2021_A_05 Page: 3.0 |
yes | |||
Sources: https://www.pmda.go.jp/PmdaSearch/iyakuDetail/ResultDataSetPDF/180188_2123404D2021_A_05 Page: 3.0 |
yes |
Sample Use Guides
In Vivo Use Guide
Sources: http://www.ncbi.nlm.nih.gov/pubmed/26703973
landiolol dosage was in the range of 0.7 µg/kg/min-to-2.5 µg/kg/min
Route of Administration:
Intravenous
In Vitro Use Guide
Sources: http://www.ncbi.nlm.nih.gov/pubmed/17201736
effects of landiolol on rat isolated aortic preparations under KCl contraction were investigated. Significant relaxations of isolated aortic preparations were obtained with landiolol 30-1000 micromol/L, suggesting a possible calcium antagonism with landiolol
Substance Class |
Chemical
Created
by
admin
on
Edited
Mon Mar 31 18:18:06 GMT 2025
by
admin
on
Mon Mar 31 18:18:06 GMT 2025
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Record UNII |
62NWQ924LH
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Record Status |
Validated (UNII)
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Classification Tree | Code System | Code | ||
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NCI_THESAURUS |
C29576
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WHO-ATC |
C07AB14
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Code System | Code | Type | Description | ||
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1545
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LANDIOLOL
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DTXSID10158026
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CHEMBL1742466
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C077049
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C79125
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m6675
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62NWQ924LH
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114905
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DB12212
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133242-30-5
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7516
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SUB08396MIG
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100000082553
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KL-159
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SALT/SOLVATE -> PARENT |
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TARGET -> INHIBITOR |
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ENANTIOMER -> ENANTIOMER |
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ACTIVE MOIETY |
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