Dioxel Mechanism of Action

Pharmacology: Pharmacodynamics: Micronized purified flavonoid fraction (MPFF) is an oral phlebotropic and vascular protective agent consisting of 90% diosmin and 10% hesperidin. It increases venous tone, improves lymphatic drainage and protects the microcirculation from inflammatory processes and apoptosis. By decreasing the expression of some endothelial adhesion molecules, MPFF inhibits the activation, migration and adhesion of leukocytes at the capillary level. This leads to a reduction in the release of inflammatory mediators such as oxygen-free radicals, prostaglandins and thromboxane resulting in a decrease in capillary hyperpermeability.
Pharmacokinetics: Diosmin is rapidly transformed in the intestine by intestinal flora and absorbed as its aglycone, diosmetin, after oral administration.
A study compared the absorption of a single oral dose of radiolabelled MPFF [500 mg tablets containing trace amounts (about 25 nCi) of ¹⁴C-diosmin] with that of nonmicronized diosmin in 12 healthy male volunteers. Results showed that about half of an oral 500 mg dose of radiolabelled MPFF was absorbed within 48 hours of administration. Since unabsorbed diosmin was not excreted in the urine, absorption was evaluated based on the urinary elimination of radioactivity. Reduction in the particle size of diosmin led to a significant increase in absorption; mean gastrointestinal absorption of micronized ¹⁴C-diosmin was significantly greater than with nonmicronized ¹⁴C-diosmin (57.9 vs. 32.7% during 0 to 168 hours postdose; p=0.004).
The time to peak plasma concentration of diosmetin is 1 hour and plasma concentrations decrease slowly after 2 hours; diosmetin is still detectable after 48 hours. The mean volume of distribution of diosmetin is 62.1 liters.
Diosmetin is rapidly and extensively degraded to phenolic acids or their glycine conjugate derivates, which are eliminated in the urine. The predominant metabolite in man is 3-hydroxy-phenylpropionic acid which is mainly eliminated in its conjugated form. Metabolites found in smaller amounts include other phenolic acids corresponding to 3-hydroxy-4-methoxybenzoic acid, 3-methoxy-4-hydroxyphenylacetic acid and 3,4-dihydroxybenzoic acid. It is possible that unidentified metabolites may be responsible for the pharmacological activity of diosmin.
Elimination of micronized diosmin is relatively rapid with ≈34% of the radiolabelled dose of ¹⁴C-diosmin excreted in the urine and feces over the first 24 hours and ≈86% over the first 48 hours. Unmetabolized diosmin and diosmetin are not excreted in the urine. The cumulative excretion of the dose in the urine and feces was 100%. About half of the dose was eliminated in the feces as unchanged diosmin and diosmetin.