Lacidipine

Lacidipine 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 peripheral arterioles, reducing peripheral vascular resistance and lowering blood pressure.

Lacidipine is a highly lipophilic compound; it is rapidly absorbed from the gastrointestinal tract following oral dosing. Absolute bioavailability averages about 10% due to extensive first-pass metabolism in the liver.

Peak plasma concentrations are reached between 30 and 150 minutes. The drug is eliminated primarily by hepatic metabolism (involving cytochrome P450 CYP3A4). There is no evidence that lacidipine causes either induction or inhibition of hepatic enzymes.

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.

The average terminal half-life of Lacidipine ranges from between 13 and 19 hours at steady state.

In acute toxicity studies, Lacidipine has shown a wide safety margin.

In repeated dose toxicological studies, findings in animals, related to the safety profile of Lacidipine in man, were reversible and reflected the pharmacodynamic effect of Lacidipine.

No data of clinical relevance have been gained from in vivo and in vitro studies on reproduction toxicity, genetic toxicity or oncogenicity.