API Benidipine Hydrochloride

Benidipine Hydrochloride More Info

Chemical identity

IUPAC name: (±)-(R*,R*)-3-[(3RS)-1-Benzylpiperidin-3-yl] 5-methyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate monohydrochloride

CAS Registry Number: 91599-74-5

Molecular formula: C₂₈H₃₁N₃O₆ · HCl

Molecular weight: 542.02 g mol⁻¹

Appearance: Yellow, crystalline powder; melting with decomposition ≈ 200 °C.

Pharmacological class

Second-generation dihydropyridine (DHP) calcium-channel blocker with simultaneous L-, N- and T-type Ca²⁺ channel blocking activity.

Mechanism of action

• High-affinity, slowly reversible binding to the DHP receptor on voltage-dependent Ca²⁺ channels.

• Inhibits Ca²⁺ influx into vascular smooth-muscle cells, leading to:

– Dilation of systemic arterioles → ↓ total peripheral resistance → sustained antihypertensive effect.

– Dilation of coronary arteries → ↑ myocardial O₂ supply → anti-anginal effect.

• Additional antioxidant, anti-aldosterone and renal-protective properties reported in experimental studies.

Pharmacokinetics at a glance

• Oral absorption: rapid, but extensive first-pass metabolism → absolute bio-availability ≈ 10 %.

• Distribution: high lipophilicity → strong membrane partitioning and long tissue residence (pharmacological effect outlasts plasma t½).

• Metabolism: hepatic CYP3A4-mediated oxidation.

• Elimination t½: ≈ 2 h (plasma); antihypertensive action persists > 24 h—attributed to tight receptor binding.

• Excretion: mainly as metabolites in urine and bile.

Therapeutic indications

• Essential hypertension.

• Chronic stable angina pectoris.

Dosage and administration (adult)

Hypertension: 2–4 mg once daily after breakfast; titrate to 8 mg once daily if required.

Angina: 4 mg twice daily after meals; adjust according to response up to 8 mg twice daily.

Elderly or hepatic impairment: initiate at the lower end of the dose range.

Contra-indications

Cardiogenic shock; unstable angina; significant aortic stenosis; pregnancy and lactation; known hypersensitivity to dihydropyridines.

Key warnings & precautions

Monitor blood pressure and heart rate on initiation. Use with caution in severe hepatic dysfunction. Grapefruit juice may increase plasma levels. Avoid co-administration with strong CYP3A4 inhibitors (e.g., clarithromycin, ritonavir).

Adverse effects

Most common (incidence < 5 %): facial flushing, palpitations, headache, dizziness, ankle oedema.

Rare but serious: hepatic dysfunction, gingival hyperplasia, hypersensitivity reactions.

Drug interactions

Additive hypotension with other antihypertensives. Plasma levels increased by CYP3A4 inhibitors and decreased by inducers. May potentiate the hypotensive effect of α-blockers and alcohol.

Pharmaceutical information

Film-coated tablets: 2 mg, 4 mg and 8 mg strengths.

Storage: protect from light and moisture; store below 30 °C.