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Identification
NameClevidipine
Accession NumberDB04920
TypeSmall Molecule
GroupsApproved
Description

Clevidipine is a dihydropyridine L-type calcium channel blocker that is selective for vascular smooth muscle and is indicated for blood pressure reduction when oral therapy is not an option.

Structure
Thumb
Synonyms
Clevidipine butyrate
External Identifiers
  • H-324/38
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Cleviprexemulsion.5 mg/mLintravenousThe Medicines Company2008-09-15Not applicableUs
Cleviprexemulsion0.5 mgintravenousThe Medicines CompanyNot applicableNot applicableCanada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNII19O2GP3B7Q
CAS number167221-71-8
WeightAverage: 456.316
Monoisotopic: 455.090242887
Chemical FormulaC21H23Cl2NO6
InChI KeyInChIKey=KPBZROQVTHLCDU-UHFFFAOYSA-N
InChI
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
IUPAC Name
methyl 5-{[(butanoyloxy)methoxy]carbonyl}-4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3-carboxylate
SMILES
CCCC(=O)OCOC(=O)C1=C(C)NC(C)=C(C1C1=CC=CC(Cl)=C1Cl)C(=O)OC
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as dihydropyridinecarboxylic acids and derivatives. These are compounds containing a dihydropyridine moiety bearing a carboxylic acid group.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassPyridines and derivatives
Sub ClassHydropyridines
Direct ParentDihydropyridinecarboxylic acids and derivatives
Alternative Parents
Substituents
  • Tricarboxylic acid or derivatives
  • Dihydropyridinecarboxylic acid derivative
  • 1,2-dichlorobenzene
  • Acylal
  • Halobenzene
  • Fatty acid ester
  • Chlorobenzene
  • Fatty acyl
  • Benzenoid
  • Monocyclic benzene moiety
  • Aryl halide
  • Aryl chloride
  • Vinylogous amide
  • Alpha,beta-unsaturated carboxylic ester
  • Enoate ester
  • Methyl ester
  • Carboxylic acid ester
  • Azacycle
  • Enamine
  • Carboxylic acid derivative
  • Acetal
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Organochloride
  • Organohalogen compound
  • Carbonyl group
  • Amine
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationFor the treatment of hypertension.
PharmacodynamicsClevidipine belongs to a well-known class of drugs called dihydropyridine calcium channel antagonists. Clevidpine is the first third generation intravenous dihydropyridine calcium channel blocker. In vitro studies demonstrated that clevidipine acts by selectively relaxing the smooth muscle cells that line small arteries, resulting in arterial dilation, widening of the artery opening, and without reducing central venous pressure or reducing cardiac output.
Mechanism of actionPossibly by deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum, clevidipine inhibits the influx of extracellular calcium across both the myocardial and vascular smooth muscle cell membranes. The resultant inhibition of the contractile processes of the myocardial smooth muscle cells leads to dilation of the coronary and systemic arteries and improved oxygen delivery to the myocardial tissue.
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein binding>99.5%
Metabolism

Clevidipine is rapidly hydrolyzed to inactive metabolites by esterases in arterial blood.

Route of eliminationurine 63-74%, feces 7-22%
Half life1 minute
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9887
Blood Brain Barrier-0.5892
Caco-2 permeable+0.6566
P-glycoprotein substrateSubstrate0.5787
P-glycoprotein inhibitor IInhibitor0.8948
P-glycoprotein inhibitor IINon-inhibitor0.6827
Renal organic cation transporterNon-inhibitor0.8312
CYP450 2C9 substrateNon-substrate0.8879
CYP450 2D6 substrateNon-substrate0.8693
CYP450 3A4 substrateSubstrate0.693
CYP450 1A2 substrateInhibitor0.6871
CYP450 2C9 inhibitorInhibitor0.6818
CYP450 2D6 inhibitorNon-inhibitor0.8455
CYP450 2C19 inhibitorInhibitor0.7456
CYP450 3A4 inhibitorInhibitor0.9187
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.9098
Ames testNon AMES toxic0.7527
CarcinogenicityNon-carcinogens0.8407
BiodegradationNot ready biodegradable0.9403
Rat acute toxicity2.6248 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7841
hERG inhibition (predictor II)Non-inhibitor0.8148
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Emulsionintravenous.5 mg/mL
Emulsionintravenous0.5 mg
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5739152 No1995-04-142015-04-14Us
US5856346 No2001-01-052021-01-05Us
US8658676 No2011-10-102031-10-10Us
Properties
StateSolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.00267 mg/mLALOGPS
logP4.98ALOGPS
logP4.09ChemAxon
logS-5.2ALOGPS
pKa (Strongest Basic)5.31ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area90.93 Å2ChemAxon
Rotatable Bond Count10ChemAxon
Refractivity113.93 m3·mol-1ChemAxon
Polarizability45.12 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
General References
  1. Zhang JG, Dehal SS, Ho T, Johnson J, Chandler C, Blanchard AP, Clark RJ Jr, Crespi CL, Stresser DM, Wong J: Human cytochrome p450 induction and inhibition potential of clevidipine and its primary metabolite h152/81. Drug Metab Dispos. 2006 May;34(5):734-7. Epub 2006 Feb 24. [PubMed:16501008 ]
  2. Nordlander M, Sjoquist PO, Ericsson H, Ryden L: Pharmacodynamic, pharmacokinetic and clinical effects of clevidipine, an ultrashort-acting calcium antagonist for rapid blood pressure control. Cardiovasc Drug Rev. 2004 Fall;22(3):227-50. [PubMed:15492770 ]
  3. Wang QD, Segawa D, Ericsson H, Sjoquist PO, Johansson L, Ryden L: Time-dependent cardioprotection with calcium antagonism and experimental studies with clevidipine in ischemic-reperfused pig hearts: part I. J Cardiovasc Pharmacol. 2002 Aug;40(2):228-34. [PubMed:12131552 ]
  4. Stephens CT, Jandhyala BS: Effects of fenoldopam, a dopamine D-1 agonist, and clevidipine, a calcium channel antagonist, in acute renal failure in anesthetized rats. Clin Exp Hypertens. 2002 May;24(4):301-13. [PubMed:12069360 ]
External Links
ATC CodesC08CA16
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelDownload (381 KB)
MSDSDownload (568 KB)
Interactions
Drug Interactions
Drug
AldesleukinThe risk or severity of adverse effects can be increased when Aldesleukin is combined with Clevidipine.
AlfuzosinAlfuzosin may increase the hypotensive activities of Clevidipine.
AmifostineClevidipine may increase the hypotensive activities of Amifostine.
AtosibanThe risk or severity of adverse effects can be increased when Clevidipine is combined with Atosiban.
Atracurium besylateClevidipine may increase the neuromuscular blocking activities of Atracurium besylate.
BepridilClevidipine may increase the hypotensive activities of Bepridil.
BrimonidineBrimonidine may increase the antihypertensive activities of Clevidipine.
ButabarbitalButabarbital may increase the hypotensive activities of Clevidipine.
ButethalButethal may increase the hypotensive activities of Clevidipine.
DapoxetineDapoxetine may increase the orthostatic hypotensive activities of Clevidipine.
DiazoxideDiazoxide may increase the hypotensive activities of Clevidipine.
DuloxetineClevidipine may increase the orthostatic hypotensive activities of Duloxetine.
EfavirenzThe serum concentration of Clevidipine can be decreased when it is combined with Efavirenz.
HeptabarbitalHeptabarbital may increase the hypotensive activities of Clevidipine.
HexobarbitalHexobarbital may increase the hypotensive activities of Clevidipine.
LevodopaClevidipine may increase the orthostatic hypotensive activities of Levodopa.
Magnesium SulfateThe risk or severity of adverse effects can be increased when Clevidipine is combined with Magnesium Sulfate.
MelatoninMelatonin may decrease the antihypertensive activities of Clevidipine.
MethohexitalMethohexital may increase the hypotensive activities of Clevidipine.
MethylphenidateMethylphenidate may decrease the antihypertensive activities of Clevidipine.
MolsidomineMolsidomine may increase the hypotensive activities of Clevidipine.
MoxonidineMoxonidine may increase the hypotensive activities of Clevidipine.
NicorandilNicorandil may increase the hypotensive activities of Clevidipine.
NitroprussideClevidipine may increase the hypotensive activities of Nitroprusside.
ObinutuzumabClevidipine may increase the hypotensive activities of Obinutuzumab.
PentobarbitalPentobarbital may increase the hypotensive activities of Clevidipine.
PentoxifyllinePentoxifylline may increase the hypotensive activities of Clevidipine.
PhenelzinePhenelzine may increase the hypotensive activities of Clevidipine.
PrazosinPrazosin may increase the hypotensive activities of Clevidipine.
PrimidonePrimidone may increase the hypotensive activities of Clevidipine.
QuinidineThe serum concentration of Quinidine can be decreased when it is combined with Clevidipine.
QuinineQuinine may increase the hypotensive activities of Clevidipine.
RisperidoneClevidipine may increase the hypotensive activities of Risperidone.
RituximabClevidipine may increase the hypotensive activities of Rituximab.
SecobarbitalSecobarbital may increase the hypotensive activities of Clevidipine.
TadalafilTadalafil may increase the antihypertensive activities of Clevidipine.
TranylcypromineTranylcypromine may increase the hypotensive activities of Clevidipine.
TreprostinilTreprostinil may increase the hypotensive activities of Clevidipine.
ValsartanThe risk or severity of adverse effects can be increased when Valsartan is combined with Clevidipine.
VardenafilVardenafil may increase the antihypertensive activities of Clevidipine.
YohimbineYohimbine may decrease the antihypertensive activities of Clevidipine.
Food Interactions
  • Grapefruit Juice

Targets

Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Voltage-gated calcium channel activity
Specific Function:
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1F gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belon...
Gene Name:
CACNA1F
Uniprot ID:
O60840
Molecular Weight:
220675.9 Da
References
  1. Nordlander M, Sjoquist PO, Ericsson H, Ryden L: Pharmacodynamic, pharmacokinetic and clinical effects of clevidipine, an ultrashort-acting calcium antagonist for rapid blood pressure control. Cardiovasc Drug Rev. 2004 Fall;22(3):227-50. [PubMed:15492770 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Voltage-gated calcium channel activity
Specific Function:
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1S gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belon...
Gene Name:
CACNA1S
Uniprot ID:
Q13698
Molecular Weight:
212348.1 Da
References
  1. Nordlander M, Sjoquist PO, Ericsson H, Ryden L: Pharmacodynamic, pharmacokinetic and clinical effects of clevidipine, an ultrashort-acting calcium antagonist for rapid blood pressure control. Cardiovasc Drug Rev. 2004 Fall;22(3):227-50. [PubMed:15492770 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Voltage-gated calcium channel activity involved sa node cell action potential
Specific Function:
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1D gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belon...
Gene Name:
CACNA1D
Uniprot ID:
Q01668
Molecular Weight:
245138.75 Da
References
  1. Nordlander M, Sjoquist PO, Ericsson H, Ryden L: Pharmacodynamic, pharmacokinetic and clinical effects of clevidipine, an ultrashort-acting calcium antagonist for rapid blood pressure control. Cardiovasc Drug Rev. 2004 Fall;22(3):227-50. [PubMed:15492770 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Voltage-gated calcium channel activity
Specific Function:
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1C gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belon...
Gene Name:
CACNA1C
Uniprot ID:
Q13936
Molecular Weight:
248974.1 Da
References
  1. Nordlander M, Sjoquist PO, Ericsson H, Ryden L: Pharmacodynamic, pharmacokinetic and clinical effects of clevidipine, an ultrashort-acting calcium antagonist for rapid blood pressure control. Cardiovasc Drug Rev. 2004 Fall;22(3):227-50. [PubMed:15492770 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Steroid hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenyto...
Gene Name:
CYP2C9
Uniprot ID:
P11712
Molecular Weight:
55627.365 Da
References
  1. Zhang JG, Dehal SS, Ho T, Johnson J, Chandler C, Blanchard AP, Clark RJ Jr, Crespi CL, Stresser DM, Wong J: Human cytochrome p450 induction and inhibition potential of clevidipine and its primary metabolite h152/81. Drug Metab Dispos. 2006 May;34(5):734-7. Epub 2006 Feb 24. [PubMed:16501008 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Steroid hydroxylase activity
Specific Function:
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.
Gene Name:
CYP2D6
Uniprot ID:
P10635
Molecular Weight:
55768.94 Da
References
  1. Zhang JG, Dehal SS, Ho T, Johnson J, Chandler C, Blanchard AP, Clark RJ Jr, Crespi CL, Stresser DM, Wong J: Human cytochrome p450 induction and inhibition potential of clevidipine and its primary metabolite h152/81. Drug Metab Dispos. 2006 May;34(5):734-7. Epub 2006 Feb 24. [PubMed:16501008 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Steroid hydroxylase activity
Specific Function:
Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic or carcinogenic forms.
Gene Name:
CYP2E1
Uniprot ID:
P05181
Molecular Weight:
56848.42 Da
References
  1. Zhang JG, Dehal SS, Ho T, Johnson J, Chandler C, Blanchard AP, Clark RJ Jr, Crespi CL, Stresser DM, Wong J: Human cytochrome p450 induction and inhibition potential of clevidipine and its primary metabolite h152/81. Drug Metab Dispos. 2006 May;34(5):734-7. Epub 2006 Feb 24. [PubMed:16501008 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Steroid hydroxylase activity
Specific Function:
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine.
Gene Name:
CYP2C19
Uniprot ID:
P33261
Molecular Weight:
55930.545 Da
References
  1. Zhang JG, Dehal SS, Ho T, Johnson J, Chandler C, Blanchard AP, Clark RJ Jr, Crespi CL, Stresser DM, Wong J: Human cytochrome p450 induction and inhibition potential of clevidipine and its primary metabolite h152/81. Drug Metab Dispos. 2006 May;34(5):734-7. Epub 2006 Feb 24. [PubMed:16501008 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N...
Gene Name:
CYP1A2
Uniprot ID:
P05177
Molecular Weight:
58293.76 Da
References
  1. Zhang JG, Dehal SS, Ho T, Johnson J, Chandler C, Blanchard AP, Clark RJ Jr, Crespi CL, Stresser DM, Wong J: Human cytochrome p450 induction and inhibition potential of clevidipine and its primary metabolite h152/81. Drug Metab Dispos. 2006 May;34(5):734-7. Epub 2006 Feb 24. [PubMed:16501008 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inducer
General Function:
Vitamin d3 25-hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular Weight:
57342.67 Da
References
  1. Zhang JG, Dehal SS, Ho T, Johnson J, Chandler C, Blanchard AP, Clark RJ Jr, Crespi CL, Stresser DM, Wong J: Human cytochrome p450 induction and inhibition potential of clevidipine and its primary metabolite h152/81. Drug Metab Dispos. 2006 May;34(5):734-7. Epub 2006 Feb 24. [PubMed:16501008 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Identical protein binding
Specific Function:
Esterase with broad substrate specificity. Contributes to the inactivation of the neurotransmitter acetylcholine. Can degrade neurotoxic organophosphate esters.
Gene Name:
BCHE
Uniprot ID:
P06276
Molecular Weight:
68417.575 Da
References
  1. Ericsson H, Tholander B, Regardh CG: In vitro hydrolysis rate and protein binding of clevidipine, a new ultrashort-acting calcium antagonist metabolised by esterases, in different animal species and man. Eur J Pharm Sci. 1999 Apr;8(1):29-37. [PubMed:10072476 ]
Comments
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Drug created on October 21, 2007 16:23 / Updated on July 01, 2016 01:52