Nicardipine Hydrochloride

Product Overview

Nicardipine Hydrochloride (development code YC-93) is a 1,4-dihydropyridine (DHP) calcium channel blocker whose chemical structure is an asymmetric diester of 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid: the 3-position is the β-(N-benzyl-N-methyl)aminoethyl ester and the 5-position is the methyl ester, as the monohydrochloride. The molecule contains one chiral center (position 4); the marketed product is the racemate (±).

Mechanism of action: It inhibits the transmembrane influx of calcium ions through specific ion channels into cardiac myocytes and vascular smooth muscle cells—the contraction of both cell types depends on extracellular calcium influx—without changing serum calcium concentration. Its selectivity for vascular smooth muscle is greater than for cardiac muscle: in animal models, nicardipine relaxes coronary vascular smooth muscle at plasma concentrations that produce almost no negative inotropic effect.

Pharmacokinetic profile (intravenous): After infusion, plasma concentration declines in a triexponential manner—rapid distribution phase α half-life about 2.7 minutes, intermediate phase β half-life about 44.8 minutes, and slow terminal phase γ half-life about 14.4 hours (detectable only after long-term infusion); total plasma clearance 0.4 L/h·kg; non-compartmental apparent volume of distribution 8.3 L/kg. Kinetics are linear over the dose range of 0.5–40 mg/h. Human plasma protein binding is >95%, and the drug is extensively metabolized by the liver. About 50% of the effect dissipates approximately 30 minutes after discontinuation (other sources record that plasma concentration falls by at least 50% within the first 2 hours after discontinuation).

Why the intravenous formulation suits emergencies: With constant-rate infusion, blood pressure begins to fall within minutes, reaching about 50% of the final reduction at about 45 minutes; the infusion rate can be adjusted for precise titration, facilitating blood pressure control within the target range in the ICU/operating room.

Technical Specifications

• Standards: CHP/USP/EP
• Specification: 0.99 (purity ≥99.0%, HPLC); ChP requires not less than 98.5% C₂₆H₂₉N₃O₆·HCl calculated on the dried basis; USP specifies 98.0%–102.0% on the dried basis (some monograph versions record 98.5%–101.0%)
• CAS Number: 54527-84-3 (EINECS 259-198-4; UNII K5BC5011K3; free base 55985-32-5)
• Molecular Formula: C₂₆H₂₉N₃O₆·HCl (some databases write the adduct form C₂₆H₃₀ClN₃O₆)
• Molecular Weight: 515.99 (consistent across ChP, USP, and EP reference standards; free base C₂₆H₂₉N₃O₆ is 479.52); exact mass 515.1823
• Appearance: Pale yellow powder or yellow crystalline powder; odorless, almost tasteless (ChP). USP and various national labels additionally describe it as a yellow to pale yellow, or yellowish-green/pale yellowish-green, odorless crystalline powder
• Purity (HPLC): ≥ 99.0%
• Melting Point:
  • ChP recorded value: 179–185 ℃, melting with decomposition (recommended)
  • FDA labels (injection/capsule): about 165–170 ℃, or about 167–171 ℃, about 169 ℃
  • Some chemical databases: 176–178 ℃
  • Differences among sources arise from measurement methods and crystal forms; state the source when comparing
• Specific Rotation: Not applicable—the marketed product is the racemate (±); position 4 of the molecule is a chiral center but the drug is administered in racemic form
• Chemical Name: 2,6-Dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid 3-[β-(N-benzyl-N-methyl)amino]ethyl 5-methyl ester hydrochloride; IUPAC: (±)-2-(benzyl-methylamino)ethyl methyl 1,4-dihydro-2,6-dimethyl-4-(m-nitrophenyl)-3,5-pyridinedicarboxylate monohydrochloride
• Solubility (ChP): Soluble in methanol, slightly soluble in ethanol and chloroform, practically insoluble in water or diethyl ether, soluble in glacial acetic acid
• Solubility (USP/labels, finer gradation): Freely soluble in methanol and glacial acetic acid (some sources include chloroform); sparingly soluble in anhydrous ethanol; slightly soluble in n-butanol, water, 0.01 M potassium dihydrogen phosphate, acetone, dioxane, and chloroform; very slightly soluble in ethyl acetate; practically insoluble in benzene, diethyl ether, and hexane. Reagent-grade solubility in DMSO about 1 mg/mL
• Calculated Physicochemical Parameters: Boiling point about 603.4 ℃ (760 mmHg); flash point about 318.7 ℃; H-bond donors 2 / acceptors 8; rotatable bonds 10; topological polar surface area about 114 Ų; heavy atom count 36
• Stability and Compatibility Notes: Dihydropyridines are light-sensitive; the API is practically insoluble in water or diethyl ether, and the injection may precipitate in admixture solutions of higher pH, so the pH of the admixture solution must be considered when diluting. Drugs reported to be incompatible include furosemide, aminophylline, heparin sodium, sodium bicarbonate, lidocaine, and various other injections
• Storage: Protect from light, seal tightly, store in a cool dark place (protected from light and not exceeding 20 ℃); reference standards and reagents are recommended to be refrigerated at 2–8 ℃

Applications

• Hypertensive emergencies (intravenous): The Chinese label indications are “emergency management of abnormal hypertension during surgery” and “hypertensive emergencies.” Dilute with normal saline or 5% dextrose injection to 0.01%–0.02% (1 mL containing 0.1–0.2 mg) and administer by intravenous drip: for abnormal hypertension during surgery, start at 2–10 μg/(kg·min), with 10–30 μg/kg intravenous bolus if necessary; for hypertensive emergencies, start at 0.5–6 μg/(kg·min) (beginning at 0.5 μg/(kg·min)), adjusting the drip rate while monitoring blood pressure
• US FDA indications and usage: Cardene IV is a calcium channel blocker indicated for the short-term treatment of hypertension when oral therapy is not feasible. For patients not receiving oral nicardipine, start at 5 mg/h, increasing by 2.5 mg/h every 5 minutes (rapid titration) to 15 minutes (slow titration), up to a maximum of 15 mg/h, until the target blood pressure reduction is achieved; discontinue if unacceptable hypotension or tachycardia occurs, and restart at 3–5 mg/h once blood pressure and heart rate stabilize. Conversion from oral nicardipine: 20 mg q8h → 0.5 mg/h, 30 mg q8h → 1.2 mg/h, 40 mg q8h → 2.2 mg/h
• EU SmPC indications focus more on critical care: Intravenous nicardipine is used for acute life-threatening hypertension, particularly malignant hypertension/hypertensive encephalopathy, aortic dissection (when short-acting beta-blockers are unsuitable, or in combination when beta-blockade alone is ineffective), and severe pre-eclampsia (when other intravenous antihypertensives are not recommended or contraindicated); it is also used for postoperative hypertension. In adults, start with a continuous infusion of 3–5 mg/h for 15 minutes, increasing by 0.5 or 1 mg every 15 minutes, with the infusion rate not exceeding 15 mg/h; once the target blood pressure is reached, gradually reduce to a maintenance rate of 2–4 mg/h
• Oral formulations (the other main outlet for the API): Capsules 20 mg and 30 mg, for monotherapy or combination treatment of hypertension; sustained-release formulations are also available (e.g., 50 mg sustained-release tablets, 100 mg/day in 2 divided doses). When transitioning from intravenous to oral therapy, the first oral dose of nicardipine may be given 1 hour before discontinuing the intravenous formulation
• Pharmacology and mechanism research: Used for in vitro and animal experiments on calcium channel blockade, vascular smooth muscle selectivity, and coronary vasodilation, as well as cardiovascular pharmacology research related to L-type calcium channels
• Formulation and manufacturing: Used for formulation development of intravenous injections (2 mL:2 mg, 10 mL:10 mg, 25 mg/10 mL i.e. 2.5 mg/mL), premixed ready-to-use infusions (0.1 mg/mL and 0.2 mg/mL in 200 mL containers), oral capsules, and sustained-release tablets; key control points include pH (3.2–4.2 or 3.5), related substances, photostability, and compatibility; suitable for analytical method development and validation, stability studies, impurity reference standards, and GMP scale-up and CMO/CDMO contract manufacturing

Safety Notice: This product is a pharmaceutical active ingredient (API) intended solely for compliant industrial, research, and pharmaceutical manufacturing use; it is not intended for end clinical use or self-medication guidance. The finished product is a prescription drug; intravenous administration must be performed by specialist physicians in medical institutions equipped for continuous blood pressure and heart rate monitoring. Contraindications: severe aortic stenosis (FDA); intracranial hemorrhage with incomplete hemostasis; increased intracranial pressure in the acute phase of stroke; hypersensitivity to this product (Chinese label); contraindicated in lactating women or breastfeeding must be discontinued during treatment. The most common adverse reactions are headache, hypotension, tachycardia, and nausea/vomiting. This product is GHS-classified as Acute Toxicity (oral/dermal/inhalation) Category 3 (H301+H311+H331); wear protective gloves, protective clothing, and respiratory protection during handling. Concomitant use with cimetidine can increase plasma concentrations; it can increase blood concentrations of ciclosporin and tacrolimus—trough level monitoring is recommended during co-administration; dose adjustment is required when used with CYP3A4 inhibitors (e.g., itraconazole, HIV protease inhibitors) or inducers (e.g., rifampicin, phenytoin). This product is not a beta-blocker and provides no protection against the dangers of abrupt beta-blocker withdrawal; beta-blockers should be tapered gradually.

Product information: please contact us. This information is for reference only.