Lacidipine

Absorption

Since it is a highly lipophilic compound, lacidpine is rapidly absorbed from the gastrointestinal tract following oral administration with the peak plasma concentrations reached between 30 and 150 minutes of dosing . The peak plasma concentrations display large interindividual variability, with the values ranging from 1.6 to 5.7 μg/L following single-dose oral administration of lacidipine 4mg in healthy young volunteers .
Absolute bioavailability is less than 10% due to extensive first-pass metabolism in the liver .

Toxicity

There have been no recorded cases of lacidipine tablets overdosage. Some of the symptoms of overdose include prolonged peripheral vasodilation associated with hypotension and tachycardia. Bradycardia or prolonged AV conduction could theoretically occur. As there is no known antidote for lacidipine, the use of standard general measures for monitoring cardiac function and appropriate supportive and therapeutic measures is recommended .
Oral LD50 in mouse, rabbit and rat are 300mg/kg, 3200mg/kg and 980mg/kg, respectively .

Description

Lacidipine is a new second-generation dihydropyridine calcium antagonist introduced as a once a day treatment for mild to moderate hypertension. It is reported to have high selectivity for vascular smooth muscle and also a long duration of action. The use of lacidipine as an antiatherosclerotic agent is currently under investigation.

Description

Lacidipine is a dihydropyridine L-type calcium channel blocker. It induces relaxation of isolated rat aorta and inhibits calcium-induced contraction of rabbit ear artery (pA₂ = 9.4). It also induces relaxation of calcium-induced contractions in isolated rat colon and bladder and guinea pig trachea (IC₅₀s = 6.7, 6, and 7.8 nM, respectively). Lacidipine induces negative inotropy in isolated guinea pig ventricular strips (IC₅₀ = 110 nM). It reduces mean blood pressure in spontaneously hypertensive rats (ED₂₅ = 0.35 mg/kg) and in renal hypertensive dogs (ED₂₅ = 0.22 mg/kg) with a transient increase in heart rate. Lacidipine inhibits copper-induced oxidation of isolated human LDL when used at concentrations of 1 and 5 μM. It reduces the extension of aortic atheromatous lesions and decreases renal injury in ApoE^-/- mice in a model of Western diet-induced atherosclerosis.

Chemical properties

White-to-Off-White Crystalline Solid

Originator

Glaxo (United Kingdom)

The Uses of Lacidipine

A dihydropyridine calcium channel blocker. Antihypertensive

The Uses of Lacidipine

antihypertensive;dihydropyridinr calcium channel blocker

The Uses of Lacidipine

A dihydropyridine calcium channel blocker. Antihypertensive.

Background

Lacidipine is a lipophilic dihydropyridine calcium antagonist with an intrinsically slow onset of activity. Due to its long duration of action, lacidipine does not lead to reflex tachycardia . It displays specificity in the vascular smooth muscle, where it acts as an antihypertensive agent to dilate peripheral arterioles and reduce blood pressure. Compared to other dihydropyridine calcium antagonists, lacidipine exhibits a greater antioxidant activity which may confer potentially beneficial antiatherosclerotic effects . Lacidipine is a highly lipophilic molecule that interacts with the biological membranes. Through radiotracer analysis, it was determined that lacidipine displays a high membrane partition coefficient leading to accumulation of the drug in the membrane and slow rate of membrane washout . When visualized by small-angle X-ray diffraction with angstrom resolution to examine its location within the membranes, lacidipine was found deep within the membrane's hydrocarbon core . These results may explain the long clinical half-life of lacidipine .
In randomised, well-controlled trials, administration of daily single-dose lacidipine ranging from 2-6 mg demonstrated comparable antihypertensive efficacy similar to that of other long-acting dihydropyridine calcium antagonists, thiazide diuretics, atenolol (a beta-blocker) and enalapril (an ACE inhibitor) . It is available as once-daily oral tablets containing 2 or 4 mg of the active compound commonly marketed as Lacipil or Motens. It is not currently FDA-approved.

Indications

Indicated for the treatment of hypertension either alone or in combination with other antihypertensive agents, including β-adrenoceptor antagonists, diuretics, and ACE-inhibitors .

What are the applications of Application

trans Lacidipine is a calcium channel protein inhibitor and blocker

Definition

ChEBI: Lacidipine is a cinnamate ester and a tert-butyl ester.

brand name

Lacipil; Lacirex; Viapres

Biochem/physiol Actions

Lacidipine is a long-acting calcium antagonist that is used in the management of hypertension. Lacidipine is a L-type Ca(2+) channel blocker belonging to 1,4-dihydropyridine class. Also, Lacidipine inhibits ryanodine receptors on the ER membrane that enhances folding, trafficking and lysosomal activity of ERAD (ER-associated degradation) misfolded lysosomal glucocerebrosidase (GS).

Pharmacokinetics

acidipine is a specific and potent calcium antagonist with a predominant selectivity for calcium channels in the vascular smooth muscle. Its main action is to dilate predominantly peripheral and coronary arteries, reducing peripheral vascular resistance and lowering blood pressure .
Following the oral administration of 4 mg lacidipine to volunteer subjects, a minimal prolongation of QTc interval has been observed (mean QTcF increase between 3.44 and 9.60 ms in young and elderly volunteers) .

Metabolism

Lacidipine undergoes complete CYP3A4-mediated hepatic metabolism, with no parent drug detected in the urine or faeces. The 2 main metabolites have no pharmacological activity .