Isradipine (DB00270): A Comprehensive Pharmacological and Clinical Monograph

1.0 Executive Summary

Isradipine is a potent, second-generation dihydropyridine (DHP) calcium channel blocker (CCB) primarily indicated for the management of mild to moderate essential hypertension. As a small molecule drug identified by DrugBank ID DB00270 and CAS Number 75695-93-1, it exerts its therapeutic effect by selectively inhibiting the influx of calcium ions through L-type calcium channels in arterial smooth muscle. This action leads to potent vasodilation, a reduction in total peripheral resistance, and a subsequent lowering of blood pressure. A key pharmacological feature of isradipine is its high degree of vasoselectivity, which confers a significant clinical advantage by minimizing the negative inotropic (cardiodepressant) effects often associated with less selective CCBs.

Despite its high potency at the receptor level, the clinical application of isradipine is shaped by a challenging pharmacokinetic profile. It is characterized by near-complete gastrointestinal absorption followed by extensive first-pass hepatic metabolism, primarily via the cytochrome P450 3A4 (CYP3A4) isoenzyme, resulting in a low and variable oral bioavailability of 15-24%. This metabolic pathway renders isradipine highly susceptible to clinically significant drug-drug and drug-food interactions. Its safety profile is largely predictable and dose-dependent, with the most common adverse effects—including peripheral edema, headache, and flushing—stemming directly from its vasodilatory mechanism of action.