Clinical Pharmacokinetics and Pharmacodynamics of Esaxerenone, a Novel Mineralocorticoid Receptor Antagonist: A Review

Esaxerenone is a selective, nonsteroidal, high-affinity mineralocorticoid receptor antagonist recently approved in Japan for the treatment of hypertension. It has high oral biovailability, a large volume of distribution, and is primarly metabolized in liver and excreted in bile. Esaxerenone is an efficient antihypertensive, whether given alone or as add-on therapy. The antihypertensive effect is accompanied by renoprotective action, which is being further investigated in current clinical trials. Due to its relatively long half-life and high affinity for the mineralocorticoid receptor, esaxerenone is administered once daily and in low absolute doses. The safety of esaxerenone is considerable, since hyperkalemia is not frequent and, when it does appear, not sustained. Endocrine adverse events, which frequently occur with steroidal mineralocorticoid receptor antagonists, are extremely rare with esaxerenone. Although the risk of clinically significant drug–drug interactions is not high, esaxerenone treatment should start with low doses, with subsequent titration to achieve the optimal clinical effect, all while monitoring serum potassium and paying attention to concomitant therapy with drugs that may induce or inhibit esaxerenone metabolism. This review article offers comprehensive information about the pharmacodynamics and pharmacokinetics of esaxerenone in humans, which should help clinicians to more precisely tailor esaxerenone dosing regimens to their patients.