Comparative Bioavailability of Two Diosmin Formulations after Oral Administration to Healthy Volunteers

Abstract

Diosmin is a flavonoid commonly found in citrus fruits, largely used as adjuvant treatment for circulatory disorders, including chronic venous insufficiency (CVI) and hemorrhoids. Following oral administration, diosmin is not directly absorbed but must first be hydrolyzed into its aglycone, diosmetin, which is then absorbed into the systemic circulation. The aim of the current cross-over clinical study was to assess the pharmacokinetic profile of µSmin® Plus, a micronized diosmin flavonoid complex standardized in diosmin and formulated with a buffering agent (tested formulation). The study compared this to unformulated micronized diosmin (reference), in 16 healthy volunteers. Plasma samples were analyzed by HPLC-MS and plasma diosmetin concentration was measured after deconjugation with β-glucuronidase. For the tested formulation area under the curve (AUC0-t), and maximum plasma and time concentration (Cmax; tmax) were found to be 298.4 ± 163.7, 50.3 ± 22.6 and 2.2 ± 2.9, respectively. AUC0-t and Cmax of the reference were 31.9 ± 100.4 and 2.4 ± 1.9, respectively. The tested formulation showed higher plasmatic concentrations of diosmetin in comparison to those obtained after the administration of unformulated micronized diosmin. The relative bioavailability was 9.4 greater for the tested formulation than in micronized diosmin. In conclusion, our data indicate that µSmin® Plus was rapidly and well absorbed into systemic circulation and may therefore be ideally suitable to deliver diosmin in human interventional trials.

Citrus Flavones: An Update on Sources, Biological Functions, and Health Promoting Properties

“…Specifically, the inhibition of drug-biotransformation CYP 450 enzymes [49] influences metabolic and pharmacokinetic properties of themselves and other simultaneously administered drugs [50]. Literature data suggest that diosmin is poorly absorbed after oral administration and this affects all pharmacokinetic parameters, including bioavailability [51]. It has been also observed that plasma concentrations have improved slightly when diosmin was administered in a micronized form, as the smaller particle size provided an increased surface area available for intestinal absorption [52].…”

Dietary natural flavonoids treating cancer by targeting aryl hydrocarbon receptor

“…Russo et al compared this with an unformulated micronized diosmin in 16 healthy volunteers. Their data indicate that lSminPlus was rapidly and well absorbed into systemic circulation (Russo et al 2018). At the same time, metabolic conversion must be considered when estimating the bioavailability and efficacy of flavonoids for pharmacological use.…”

Bioavailability and Metabolism of Food Bioactives and their Health Effects: A Review

“…Therefore, the enzyme specificity and distribution play a vital role in flavonoid absorption. In most cases, it is reported that in brush borders of intestine and absorption in the liver, flavonoids undergo phase II metabolism to form various glucuronides, sulfates or methylated derivatives (Koutsos et al, 2015;Russo et al, 2018;Scalbert and Williamson, 2000). The small intestine directly absorbs low-molecular-weight flavonoids; however, high-molecular-weight flavonoids reach the colon almost unchanged, and they are hydrolyzed by intense metabolic activity before absorption.…”