Comprehensive Monograph on Diosmin (DB08995)

1.0 Executive Summary

Diosmin is a naturally derived flavonoid glycoside, classified therapeutically as a venoactive and vasoprotective agent, commonly referred to as a phlebotonic. Its primary clinical applications are in the management of chronic venous insufficiency (CVI) and both acute and chronic hemorrhoidal disease. Sourced primarily through the semi-synthetic modification of hesperidin from citrus peels, diosmin has a long history of use, particularly in Europe, where it is regulated as a prescription or over-the-counter medicinal product.

The pharmacological activity of diosmin is multifaceted, targeting the key pathophysiological elements of venous disease. Its mechanism of action includes enhancing venous tone by prolonging the vasoconstrictive effects of noradrenaline, reducing capillary hyperpermeability and increasing capillary resistance, and improving lymphatic drainage. Beyond these hemodynamic effects, diosmin exerts significant anti-inflammatory and antioxidant activities. It modulates critical inflammatory pathways, reducing the synthesis of prostaglandins and the expression of endothelial adhesion molecules, and has been shown in clinical studies to decrease plasma levels of key pro-inflammatory cytokines and pro-angiogenic factors.

A critical aspect of its pharmacology is its pharmacokinetic profile. Diosmin functions as a prodrug; in its native glycoside form, it is poorly absorbed. Following oral administration, it requires hydrolysis by intestinal microflora to release its active aglycone, diosmetin, which is then absorbed into the systemic circulation. This conversion is the rate-limiting step for its bioavailability, a challenge that has led to the development of advanced formulations such as micronized purified flavonoid fraction (MPFF).