Diosmin and Hesperidin: What Does Pharmacokinetics Show?
Flavonoids are plant-derived compounds that have a number of beneficial pharmacological effects. Among the most well-known flavonoids, alongside rutin, are diosmin and hesperidin, which are used as venotonics and vasoprotectives in chronic venous insufficiency (CVI).
Introduction
Chronic venous insufficiency is a disease with high prevalence, yet without causal treatment. In the initial stages, compression therapy supplemented by pharmacotherapy is particularly important, where these flavonoids are used to improve venous tone, lymphatic drainage, and reduce capillary hyperpermeability.
Diosmin and Hesperidin
Hesperidin is extracted from citrus fruits (the name is derived from the Latin word hesperidium for the characteristic citrus fruit), which is then dehydrogenated to produce diosmin. Other products are simultaneously formed in the reaction, thus the resulting mixture is known as the “flavonoid fraction.” For therapeutic purposes, it is most beneficial to administer a product with a predominance of diosmin. The European Pharmacopoeia precisely defines the proportion of impurities (other flavonoids) that diosmin used for pharmaceutical purposes may contain. Among these impurities is hesperidin, which may account for a maximum of 4%.
After oral administration of flavonoids, the sugar component is hydrolytically cleaved by intestinal microbiota, forming their metabolites, known as aglycones. The aglycone of diosmin is called diosmetin, and the aglycone of hesperidin is hesperetin; both of these substances significantly differ in terms of pharmacokinetics.
Pharmacokinetic Properties and Their Impact on Therapeutic Practice
Pharmacokinetics describes the fate of a drug in the body from its administration to its elimination. For a drug to be effective, it must be present in the body. This so-called bioavailability is expressed as the proportion of the administered dose that reaches the systemic circulation. The higher the percentage, the more substance will be available in the body for use. The degree of bioavailability of a drug after oral administration depends on a number of factors. In the case of flavonoids, bioavailability is significantly increased by micronization — a process of reducing particle size to micrometers, leading to an increase in active surface area and improved solubility, thus resulting in faster and more effective absorption.
Pharmacokinetic studies have shown that diosmin is rapidly transformed by intestinal microbiota into diosmetin, which is then quickly absorbed and distributed throughout the body — the bioavailability of micronized diosmin is approximately 65%. Diosmetin has a distribution volume of 62 liters, indicating wide distribution into tissues, and an elimination half-life of 26–43 hours. A pharmacokinetic study with hesperetin on 6 healthy volunteers, on the other hand, showed that its bioavailability is lower and the elimination half-life is 3 hours.
Conclusion
Pharmacokinetic parameters of the active forms of venotonic flavonoids diosmin and hesperidin indicate that diosmin and its metabolite diosmetin may have a stronger and more prolonged effect on the venous wall.
(jvi)
Sources:
1. Cova D., DeAngelis L., Giavarini F. et al. Pharmacokinetics and metabolism of oral diosmin in healthy volunteers. Int J Clin Pharmacol Ther Toxicol 1992; 30 (1): 29–33.
2. Kanaze F. I., Bounartzi M. I., Georgarakis M., Niopas I. Pharmacokinetics of the citrus flavanone aglycones hesperetin and naringenin after single oral administration in human subjects. Eur J Clin Nutr 2007; 61: 472–477, doi: 10.1038/sj.ejcn.1602543.
3. Diosmin. European Pharmacopoeia, 9th ed. Council of Europe, Strasbourg, 2017: 2286–2287.
4. SPC of products with diosmin.
Did you like this article? Would you like to comment on it? Write to us. We are interested in your opinion. We will not publish it, but we will gladly answer you.
