Clevidipine (Cleviprex) is a potent and short acting, dihydropyridine-based L-type calcium channel blocker used for reducing blood pressure when oral therapy is not feasible or not desirable. Clevidipine is highly selective for vascular, as opposed to myocardial, smooth muscle and, therefore, has little or no effect on myocardial contractility or cardiac conduction. It was approved by the FDA on August 1, 2008 as an antihypertensive agent for the reduction of blood pressure.

Physicochemical Properties

Molecular Formula	C21H23CL2NO6
Molecular Weight	456.32
Exact Mass	455.09
CAS #	167221-71-8
Related CAS #	Clevidipine-d7;(R)-Clevidipine-13C,d3
PubChem CID	153994
Appearance	White to off-white solid powder
Density	1.3±0.1 g/cm3
Boiling Point	539.7±50.0 °C at 760 mmHg
Melting Point	128-130°C
Flash Point	280.2±30.1 °C
Vapour Pressure	0.0±1.4 mmHg at 25°C
Index of Refraction	1.543
LogP	5.46
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	10
Heavy Atom Count	30
Complexity	748
Defined Atom Stereocenter Count	0
InChi Key	KPBZROQVTHLCDU-UHFFFAOYSA-N
InChi Code	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
Chemical Name	methyl 5-{[(butanoyloxy)methoxy]carbonyl}-4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3-carboxylate
Synonyms	Clevidipine; Clevidipine butyrate; Cleviprex; Clevelox; Rac-Clevidipine
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: This product requires protection from light (avoid light exposure) during transportation and storage.
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro	In vitro: Both clevidipine and nitroglycerin completely reversed U46619-induced contraction (clevidipine (50% effective concentration [EC50] = 3.88 +/- 0.84 x 10(-6) mol/L, nitroglycerin EC50 = 4.84 +/- 2.76 x 10(-8) mol/L). A decrease in temperature increased the half-life of clevidipine in blood, whereas dilution of the blood did not affect the in vitro half-life of clevidipine. The albumin concentration affected the hydrolysis rate of clevidipine in RBC suspended with saline
ln Vivo	Clevidipine is a high-clearance drug with a relatively small volume of distribution, resulting in an extremely short half-life in all species studied. The median initial half-life of the individual value (Bayesian estimates) is 12, 20, and 22 s in the rabbit, rat, and dog, respectively. The extremely high clearance value and the small volume of distribution resulted in short half-lives of clevidipine, 2.2 and 16.8 min, respectively. The blood concentration and dose rate producing half the maximal effect (i.e. EC50 and ED50) were approximately 25 nM and 1.5 microg/kg/min, respectively.
Animal Protocol	PK studies Rabbit, rat, and dog
ADME/Pharmacokinetics	Absorption, Distribution and Excretion urine 63-74%, feces 7-22% Metabolism / Metabolites Clevidipine is rapidly hydrolyzed to inactive metabolites by esterases in arterial blood. Biological Half-Life 1 minute
Toxicity/Toxicokinetics	Protein Binding >99.5%
References	J Pediatr Pharmacol Ther.2015Jan-Feb;20(1):54-60.
Additional Infomation	Clevidipine is a dihydropyridine. 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. Clevidipine is a Dihydropyridine Calcium Channel Blocker. The mechanism of action of clevidipine is as a Calcium Channel Antagonist. Drug Indication For the reduction of blood pressure when when oral antihypertensive therapy is not feasible or not desirable. FDA Label Treatment of hypertensive disease Mechanism of Action Possibly 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. Pharmacodynamics Clevidipine 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.

Solubility Data

Solubility (In Vitro)

DMSO: 91 mg/mL (199.4 mM) Water:< 1 mg/mL Ethanol:3 mg/mL (6.6 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.48 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 25.0 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: ≥ 2.5 mg/mL (5.48 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.1914 mL	10.9572 mL	21.9144 mL
	5 mM	0.4383 mL	2.1914 mL	4.3829 mL
	10 mM	0.2191 mL	1.0957 mL	2.1914 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.