Indications
Cilnidipine is primarily indicated for the management of hypertension, with a focus on end-organ protection. It has proven particularly beneficial for elderly patients, as well as those with diabetes and albuminuria. Its usage is increasingly prevalent among individuals suffering from chronic kidney disease. Hypertension, the condition characterized by elevated blood pressure, results from the excessive force of blood against the vessel walls, leading to potential vascular damage.
Pharmacodynamics
In terms of pharmacodynamics, cilnidipine demonstrates an antisympathetic effect both in vitro and in vivo. It effectively reduces blood pressure without causing excessive hypotension or inducing tachycardia, ensuring safer management of hypertension compared to some other therapies.
Absorption
Cilnidipine exhibits rapid absorption, reaching peak plasma concentrations approximately two hours after administration. It distributes broadly across various tissues, including the liver, kidneys, and plasma. Importantly, cilnidipine does not accumulate significantly in tissues following repeated oral doses. Its bioavailability is relatively low, estimated at about 13%, primarily due to limited aqueous solubility and high permeability. Innovative formulations, like the development of polymeric nanoparticles, have been explored to enhance its bioavailability by 2.5 to 3 times.
Metabolism
The metabolism of cilnidipine occurs primarily in the liver and kidneys. Within the liver, it undergoes rapid dehydrogenation through liver microsomes, with the enzyme CYP3A playing a major role in this process. The involvement of these metabolic pathways underscores the complex pharmacokinetic profile of cilnidipine.
Mechanism of Action
Cilnidipine functions by targeting the L-type calcium channels within blood vessels, effectively blocking calcium influx and thereby inhibiting vascular contraction, resulting in a reduction of blood pressure. Additionally, Cilnidipine influences the N-type calcium channels located at the terminals of sympathetic nerves, curbing the release of norepinephrine, which assists in moderating stress-induced increases in blood pressure.
