Details
| Stereochemistry | RACEMIC |
| Molecular Formula | C21H23Cl2NO6 |
| Molecular Weight | 456.316 |
| Optical Activity | ( + / - ) |
| Defined Stereocenters | 0 / 1 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
CCCC(=O)OCOC(=O)C1=C(C)NC(C)=C(C1C2=CC=CC(Cl)=C2Cl)C(=O)OC
InChI
InChIKey=KPBZROQVTHLCDU-UHFFFAOYSA-N
InChI=1S/C21H23Cl2NO6/c1-5-7-15(25)29-10-30-21(27)17-12(3)24-11(2)16(20(26)28-4)18(17)13-8-6-9-14(22)19(13)23/h6,8-9,18,24H,5,7,10H2,1-4H3
Clevidipine is a dihydropyridine calcium channel blocker. Clevidipine is marketed under the trade name Cleviprex, indicated for the reduction of blood pressure (BP) when oral therapy is not feasible or not desirable. Clevidipine is a dihydropyridine L-type calcium channel blocker. L-type calcium channels mediate the influx of calcium during depolarization in arterial smooth muscle. Experiments in anesthetized rats and dogs show that clevidipine reduces mean arterial blood pressure by decreasing systemic vascular resistance. Clevidipine does not reduce cardiac filling pressure (pre-load), confirming lack of effects on the venous capacitance vessels.
Originator
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: CHEMBL2095229 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19331440 |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Primary | CLEVIPREX Approved UseCleviprex is indicated for the reduction of blood pressure when oral therapy is not feasible or not desirable. Cleviprex is a dihydropyridine calcium channel blocker indicated for the reduction of blood pressure when oral therapy is not feasible or not desirable. (1) Launch Date2008 |
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
3.36 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22457015/ |
2 mg/h other, intravenous dose: 2 mg/h route of administration: Intravenous experiment type: OTHER co-administered: |
CLEVIDIPINE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
122 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22457015/ |
2 mg/h other, intravenous dose: 2 mg/h route of administration: Intravenous experiment type: OTHER co-administered: |
CLEVIDIPINE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
T1/2
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
4.18 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22457015/ |
2 mg/h other, intravenous dose: 2 mg/h route of administration: Intravenous experiment type: OTHER co-administered: |
CLEVIDIPINE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
15 min |
2 mg/h other, intravenous dose: 2 mg/h route of administration: Intravenous experiment type: OTHER co-administered: |
CLEVIDIPINE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
Funbound
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
0.5% |
2 mg/h other, intravenous dose: 2 mg/h route of administration: Intravenous experiment type: OTHER co-administered: |
CLEVIDIPINE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
Doses
| Dose | Population | Adverse events |
|---|---|---|
9.58 ug/kg/min 1 times / day single, intravenous Recommended Dose: 9.58 ug/kg/min, 1 times / day Route: intravenous Route: single Dose: 9.58 ug/kg/min, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sex: M+F Sources: |
Disc. AE: Hypotension, Hypertension... AEs leading to discontinuation/dose reduction: Hypotension Sources: Hypertension Haemorrhage Flushing Pallor Atrial fibrillation Ventricular fibrillation Bradycardia Myocardial infarction Tachycardia Supraventricular tachycardia Atrial flutter Atrioventricular block complete Atrioventricular block second degree Cardiac failure congestive Cardio-respiratory arrest Low cardiac output syndrome Myocardial ischaemia Supraventricular extrasystoles Ventricular tachycardia Hypoxia Acute respiratory failure Pulmonary hypertension Respiratory arrest Incision site complication Thrombocytopenia |
AEs
| AE | Significance | Dose | Population |
|---|---|---|---|
| Acute respiratory failure | Disc. AE | 9.58 ug/kg/min 1 times / day single, intravenous Recommended Dose: 9.58 ug/kg/min, 1 times / day Route: intravenous Route: single Dose: 9.58 ug/kg/min, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sex: M+F Sources: |
| Atrial fibrillation | Disc. AE | 9.58 ug/kg/min 1 times / day single, intravenous Recommended Dose: 9.58 ug/kg/min, 1 times / day Route: intravenous Route: single Dose: 9.58 ug/kg/min, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sex: M+F Sources: |
| Atrial flutter | Disc. AE | 9.58 ug/kg/min 1 times / day single, intravenous Recommended Dose: 9.58 ug/kg/min, 1 times / day Route: intravenous Route: single Dose: 9.58 ug/kg/min, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sex: M+F Sources: |
| Atrioventricular block complete | Disc. AE | 9.58 ug/kg/min 1 times / day single, intravenous Recommended Dose: 9.58 ug/kg/min, 1 times / day Route: intravenous Route: single Dose: 9.58 ug/kg/min, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sex: M+F Sources: |
| Atrioventricular block second degree | Disc. AE | 9.58 ug/kg/min 1 times / day single, intravenous Recommended Dose: 9.58 ug/kg/min, 1 times / day Route: intravenous Route: single Dose: 9.58 ug/kg/min, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sex: M+F Sources: |
| Bradycardia | Disc. AE | 9.58 ug/kg/min 1 times / day single, intravenous Recommended Dose: 9.58 ug/kg/min, 1 times / day Route: intravenous Route: single Dose: 9.58 ug/kg/min, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sex: M+F Sources: |
| Cardiac failure congestive | Disc. AE | 9.58 ug/kg/min 1 times / day single, intravenous Recommended Dose: 9.58 ug/kg/min, 1 times / day Route: intravenous Route: single Dose: 9.58 ug/kg/min, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sex: M+F Sources: |
| Cardio-respiratory arrest | Disc. AE | 9.58 ug/kg/min 1 times / day single, intravenous Recommended Dose: 9.58 ug/kg/min, 1 times / day Route: intravenous Route: single Dose: 9.58 ug/kg/min, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sex: M+F Sources: |
| Flushing | Disc. AE | 9.58 ug/kg/min 1 times / day single, intravenous Recommended Dose: 9.58 ug/kg/min, 1 times / day Route: intravenous Route: single Dose: 9.58 ug/kg/min, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sex: M+F Sources: |
| Haemorrhage | Disc. AE | 9.58 ug/kg/min 1 times / day single, intravenous Recommended Dose: 9.58 ug/kg/min, 1 times / day Route: intravenous Route: single Dose: 9.58 ug/kg/min, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sex: M+F Sources: |
| Hypertension | Disc. AE | 9.58 ug/kg/min 1 times / day single, intravenous Recommended Dose: 9.58 ug/kg/min, 1 times / day Route: intravenous Route: single Dose: 9.58 ug/kg/min, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sex: M+F Sources: |
| Hypotension | Disc. AE | 9.58 ug/kg/min 1 times / day single, intravenous Recommended Dose: 9.58 ug/kg/min, 1 times / day Route: intravenous Route: single Dose: 9.58 ug/kg/min, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sex: M+F Sources: |
| Hypoxia | Disc. AE | 9.58 ug/kg/min 1 times / day single, intravenous Recommended Dose: 9.58 ug/kg/min, 1 times / day Route: intravenous Route: single Dose: 9.58 ug/kg/min, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sex: M+F Sources: |
| Incision site complication | Disc. AE | 9.58 ug/kg/min 1 times / day single, intravenous Recommended Dose: 9.58 ug/kg/min, 1 times / day Route: intravenous Route: single Dose: 9.58 ug/kg/min, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sex: M+F Sources: |
| Low cardiac output syndrome | Disc. AE | 9.58 ug/kg/min 1 times / day single, intravenous Recommended Dose: 9.58 ug/kg/min, 1 times / day Route: intravenous Route: single Dose: 9.58 ug/kg/min, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sex: M+F Sources: |
| Myocardial infarction | Disc. AE | 9.58 ug/kg/min 1 times / day single, intravenous Recommended Dose: 9.58 ug/kg/min, 1 times / day Route: intravenous Route: single Dose: 9.58 ug/kg/min, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sex: M+F Sources: |
| Myocardial ischaemia | Disc. AE | 9.58 ug/kg/min 1 times / day single, intravenous Recommended Dose: 9.58 ug/kg/min, 1 times / day Route: intravenous Route: single Dose: 9.58 ug/kg/min, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sex: M+F Sources: |
| Pallor | Disc. AE | 9.58 ug/kg/min 1 times / day single, intravenous Recommended Dose: 9.58 ug/kg/min, 1 times / day Route: intravenous Route: single Dose: 9.58 ug/kg/min, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sex: M+F Sources: |
| Pulmonary hypertension | Disc. AE | 9.58 ug/kg/min 1 times / day single, intravenous Recommended Dose: 9.58 ug/kg/min, 1 times / day Route: intravenous Route: single Dose: 9.58 ug/kg/min, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sex: M+F Sources: |
| Respiratory arrest | Disc. AE | 9.58 ug/kg/min 1 times / day single, intravenous Recommended Dose: 9.58 ug/kg/min, 1 times / day Route: intravenous Route: single Dose: 9.58 ug/kg/min, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sex: M+F Sources: |
| Supraventricular extrasystoles | Disc. AE | 9.58 ug/kg/min 1 times / day single, intravenous Recommended Dose: 9.58 ug/kg/min, 1 times / day Route: intravenous Route: single Dose: 9.58 ug/kg/min, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sex: M+F Sources: |
| Supraventricular tachycardia | Disc. AE | 9.58 ug/kg/min 1 times / day single, intravenous Recommended Dose: 9.58 ug/kg/min, 1 times / day Route: intravenous Route: single Dose: 9.58 ug/kg/min, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sex: M+F Sources: |
| Tachycardia | Disc. AE | 9.58 ug/kg/min 1 times / day single, intravenous Recommended Dose: 9.58 ug/kg/min, 1 times / day Route: intravenous Route: single Dose: 9.58 ug/kg/min, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sex: M+F Sources: |
| Thrombocytopenia | Disc. AE | 9.58 ug/kg/min 1 times / day single, intravenous Recommended Dose: 9.58 ug/kg/min, 1 times / day Route: intravenous Route: single Dose: 9.58 ug/kg/min, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sex: M+F Sources: |
| Ventricular fibrillation | Disc. AE | 9.58 ug/kg/min 1 times / day single, intravenous Recommended Dose: 9.58 ug/kg/min, 1 times / day Route: intravenous Route: single Dose: 9.58 ug/kg/min, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sex: M+F Sources: |
| Ventricular tachycardia | Disc. AE | 9.58 ug/kg/min 1 times / day single, intravenous Recommended Dose: 9.58 ug/kg/min, 1 times / day Route: intravenous Route: single Dose: 9.58 ug/kg/min, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sex: M+F Sources: |
Overview
| CYP3A4 | CYP2C9 | CYP2D6 | hERG |
|---|---|---|---|
OverviewOther
| Other Inhibitor | Other Substrate | Other Inducer |
|---|---|---|
Drug as perpetrator
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
Page: 10, 14 |
likely [Ki 4 uM] | |||
Page: 10, 14 |
likely [Ki 6.5 uM] | |||
Page: 5.0 |
no | |||
Page: 5.0 |
no | |||
Page: 80.0 |
yes | |||
Page: 5.0 |
yes |
Tox targets
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
Page: 87.0 |
PubMed
| Title | Date | PubMed |
|---|---|---|
| New therapeutic perspectives with clevidipine: an ultra-short-acting intravenous Ca2+ channel blocker. | 2007-09 |
|
| Human cytochrome p450 induction and inhibition potential of clevidipine and its primary metabolite h152/81. | 2006-05 |
|
| Pharmacodynamic, pharmacokinetic and clinical effects of clevidipine, an ultrashort-acting calcium antagonist for rapid blood pressure control. | 2004 |
|
| Time-dependent cardioprotection with calcium antagonism and experimental studies with clevidipine in ischemic-reperfused pig hearts: part I. | 2002-08 |
|
| Effects of fenoldopam, a dopamine D-1 agonist, and clevidipine, a calcium channel antagonist, in acute renal failure in anesthetized rats. | 2002-05 |
Patents
Sample Use Guides
Initial dose: Initiate the intravenous infusion of Cleviprex at 1-2 mg/hour.
Dose titration: The dose may be doubled at short (90 second) intervals initially. As the blood pressure approaches goal, the increase in doses should be less than doubling and the time between dose adjustments should be lengthened to every 5-10 minutes. An approximately 1-2 mg/hour increase will generally produce an additional 2-4 mmHg decrease in systolic pressure.
Maintenance dose: The desired therapeutic response for most patients occurs at doses of 4-6 mg/hour. Patients with severe hypertension may require doses up to 32 mg/hour, but there is limited experience at this dose rate.
Maximum dose: Most patients were treated with maximum doses of 16 mg/hour or less.There is limited short-term experience with doses up to 32 mg/hour. Because of lipid load restrictions, no more than 1000 mL or an average of 21 mg/hour of Cleviprex infusion is recommended per 24 hour period. In clinical trials, 55 hypertensive patients were treated with >500mL of Cleviprex infusion per 24 hour period. There is little experience with infusion durations beyond 72 hours at any dose.
Route of Administration:
Intravenous
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/9356090
Clevidipine completely reversed U46619-induced contraction (EC50 = 3.88 +/- 0.84 x 10(-6) mol/L) of human internal mammary artery.
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| Classification Tree | Code System | Code | ||
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NDF-RT |
N0000007556
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WHO-ATC |
C08CA16
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NDF-RT |
N0000175421
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NDF-RT |
N0000000069
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NCI_THESAURUS |
C333
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WHO-VATC |
QC08CA16
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7468
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DB04920
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7490
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CHEMBL1237132
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C72727
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100000080215
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Clevidipine
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19O2GP3B7Q
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233603
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C118563
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167221-71-8
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m3620
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ACTIVE MOIETY
METABOLITE (PARENT)