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.
Chemical Properties
White-to-Off-White Crystalline Solid
Originator
Glaxo (United Kingdom)
Uses
A dihydropyridine calcium channel blocker. Antihypertensive
Uses
antihypertensive;dihydropyridinr calcium channel 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).
Drug interactions
Potentially hazardous interactions with other drugs
Aminophylline and theophylline: possibly increased
aminophylline and theophylline concentration.
Anaesthetics: enhanced hypotensive effect.
Antibacterials: metabolism possibly inhibited by
clarithromycin, erythromycin and telithromycin.
Antidepressants: enhanced hypotensive effect with
MAOIs.
Antiepileptics: effect possibly reduced by
carbamazepine, barbiturates, phenytoin and
primidone.
Antifungals: metabolism possibly inhibited by
itraconazole and ketoconazole; negative inotropic
effect possibly increased with itraconazole.
Antihypertensives: enhanced hypotensive effect,
increased risk of first dose hypotensive effect of postsynaptic alpha-blockers.
Antivirals: concentration possibly increased by
ritonavir.
Ciclosporin: 10 kidney transplant patients on
ciclosporin, prednisone and azathioprine were given
4 mg lacidipine daily. A very small increase in the
trough serum levels (+6%) and AUC (+14%) of the
ciclosporin occurred.
Grapefruit juice: concentration increased - avoid
concomitant use
Metabolism
Lacidipine undergoes extensive first-pass metabolism
in the liver. The drug is eliminated primarily by hepatic
metabolism (involving cytochrome P450 CYP3A4).
The principal metabolites possess little, if any,
pharmacodynamic activity.
Approximately 70% of the administered dose is
eliminated as metabolites in the faeces and the remainder
as metabolites in the urine.
