BACKGROUND: Venotonics are a class of therapeutically active molecules that have vaso-protective effects. They are used to alleviate venous diseases and disorders, particularly venous insufficiency. We compared the composition of prescription versus over-the-counter (OTC) venotonics using high-performance liquid chromatography with UV detection (HPLC-DAD) and simulating their digestion using a static digestive model. METHODS: From each drug, five tablets were weighed. A homogenate was prepared, and 25 mg of crushed homogenized tablets were weighed into 25 ml volumetric flasks. Dissolved in MeOH and added two drops of saturated NaOH solution. The samples were filtered into vials (Teflon, 0.45 μm) and used for analysis. An Ultimate 3000 HPLC system (Thermo Fisher Scientific, Waltham, MA, USA) consisting of a quaternization pump, autosampler, column thermostat and DAD (UV/VIS detector) was used. The composition of the mobile phase proceeded in a linear gradient from 30% methanol and 70% phosphoric acid (0.15%) in water at time t=0 min. to 80% methanol and 20% phosphoric acid (0.15%) at time t=15 min., at a constant mobile phase flow rate of 1.2 mL/min. Detection was performed using a DAD detector in the 190-450 nm wavelength range. The content of monitored flavonoids was calculated from peaks at a wavelength of 277 nm, in which both flavonoids have their absorption maxima. The static digestive model was used to simulate the digestive phase from the oral cavity to the corresponding intestinal phase. RESULTS: The content of diosmin and hesperidin (mg per table) for a prescription drug: Detralex: 480 mg, 26 mg. The content of diosmin and hesperidin (mg per tablet) for OTC drugs: Venostop: 502 mg, 48 mg, Diosminol: 520 mg, 50 mg, Devenal: 496 mg, 49 mg, Diohes: 493 mg, 46 mg. Digestion did not affect the solubility of all tested drugs. The active substances could not be determined in the non-alkalized sample. After alkalization, part of the insoluble matter was visibly dissolved and converted to a yellow flavonoid complex. Neither diosmin nor hesperidin could be identified afterwards. CONCLUSIONS: Our experimental results show that the contents of both listed active substances, diosmin and hesperidin, met the declared amounts in all tested medicaments. Digestion simulation showed identical behaviour in prescription and OTC venotonics. The active substances could not be determined in the non-alkalized sample. Digestion did not affect the solubility of the tested drugs.

• MeSH
• biologické modely MeSH
• diosmin analýza   MeSH
• hesperidin analýza   MeSH
• léky bez předpisu * chemie   MeSH
• léky na předpis analýza   chemie   MeSH
• lidé MeSH
• tablety MeSH
• vysokoúčinná kapalinová chromatografie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• Názvy látek
• diosmin MeSH
• hesperidin MeSH
• léky bez předpisu * MeSH
• léky na předpis MeSH
• tablety MeSH

Metabolic syndrome is diagnosed mainly in people of economically developed parts of the world and it affects 20-25% of the adult population worldwide. Nowadays, it is also more frequently diagnosed in children and adolescents. In addition to standard treatment that often involves polypharmacotherapy, and thus increases risk of side effects caused by drugdrug interactions, it is appropriate to look for alternative tools to support the treatment of metabolic syndrome components. Natural polyphenolic compounds, usually present in the so-called functional foods, are suitable candidates for that matter, due to the bioactivity and beneficial effects on the human body. Quercetin, troxerutin, diosmin, hesperidin or silybin are among the currently studied and used natural polyphenolic compounds with a positive effect on aspects of the metabolic syndrome. In addition to their antioxidant and anti-inflammatory effects, these compounds have other positive properties that very often outweigh their side effects whilst their usage in the pharmacotherapy.

• Klíčová slova
• NAFLD, diosmin, metabolic syndrome, polyphenolic compounds, quercetin, silymarin, troxerutin,
• MeSH
• antiflogistika MeSH
• antioxidancia škodlivé účinky   MeSH
• diosmin * terapeutické užití   MeSH
• dítě MeSH
• dospělí MeSH
• hesperidin * terapeutické užití   MeSH
• lidé MeSH
• metabolický syndrom * farmakoterapie   MeSH
• mladiství MeSH
• quercetin MeSH
• silibinin terapeutické užití   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antiflogistika MeSH
• antioxidancia MeSH
• diosmin * MeSH
• hesperidin * MeSH
• quercetin MeSH
• silibinin MeSH

With the advent of novel monocomponent venoactive drugs containing the flavonoid diosmin, the need has arisen to answer the question of therapeutic equivalence of the widely used micronized purified flavonoid fraction (MPFF) contained in Detralex and of the currently introduced monocomponent venoactive drugs. Experimental work provides evidence that each of the two dominant components, i.e. diosmin and hesperidin, has its specific and distinctive pharmacodynamic effect. There is also evidence of a mutual synergistic effect, e.g. in antiexudative action. Clinical studies have been carried out with MPFF for the most part, and effect has clearly been established in this particular form. Conversely, the results of studies documenting the effect of diosmin alone have been conflicting. Mutual comparisons failed to confirm equivalence of MPFF and monocomponent diosmin in any of the studies. This fact is clearly reflected in the relevant guidelines where the use of MPFF in chronic venous disease is recommended unequivocally (level of evidence 1 and strength of evidence B) while, in the case of monocomponent diosmin, it is stated that treatment can be considered (2C). It can be concluded that both experimental and clinical studies document that only a complex of biologically active flavonoids - a micronized purified flavonoid fraction - has evidence of effect and is recommended by relevant guidelines.

• Klíčová slova
• chronic venous disease, diosmin, equivalence, hesperidin, micronized purified flavonoid fraction,
• MeSH
• chronická nemoc MeSH
• diosmin * farmakologie   MeSH
• flavonoidy MeSH
• hesperidin * farmakologie   MeSH
• lidé MeSH
• nemoci cév * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• diosmin * MeSH
• flavonoidy MeSH
• hesperidin * MeSH

Chronic venous insufficiency is a highly prevalent disease in the western population. Unfortunately, there is no causal treatment yet. A key role in the recommended therapeutic approaches, especially in the early stages, is the compression therapy accompanied by pharmacotherapy. This includes, inter alia, micronized diosmin. The following text summarizes the basic knowledge of its properties that determine its clinical use.

• Klíčová slova
• chronic venous insufficiency, diosmin, flavonoids, micronization,
• MeSH
• diosmin * terapeutické užití   MeSH
• flavonoidy MeSH
• lidé MeSH
• prevalence MeSH
• žilní insuficience * farmakoterapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• diosmin * MeSH
• flavonoidy MeSH

Phytochemicals are widely present in fruits, vegetables and other plants and have great health benefits owing to their antioxidant properties. They are naturally found in the aquatic environment as well as discharged from sewage treatment plants after their large consumption. Little is known about their impact on fish; particularly in light of their interactions with pharmaceuticals. Therefore, this study was designed to determine the effects of diosmin, naringenin, quercetin and idole-3-carbinol on CYP1A-dependent 7-ethoxyresorufin-O-deethylase (EROD) activity on rainbow trout hepatic microsomes in the presence of two pharmaceuticals: clotrimazole and dexamethasone. The interactions between the phytochemicals and pharmaceuticals used in this study were determined using a combination index. Hepatic microsomes were exposed to two concentrations (1-or 50 μM) of phytochemicals and pharmaceuticals separately and in combinations. Singly, clotrimazole inhibited EROD activity 40% and 90% of control, while dexamethasone did not. Naringenin and diosmin inhibited EROD activity alone up to 90% and 55% respectively, but activities were further inhibited in the presence of either pharmaceutical. The preliminary study of combinations of clotrimazole with phytochemicals primarily showed synergistic effects. While EROD activity was not inhibited in the presence of quercetin or indole-3-carbinol, significant and synergistic inhibition was detected when either of these was combined with clotrimazole or dexamethasone.

• Klíčová slova
• Combination index, EROD, Inhibition, Interaction, Pharmaceuticals, Phytochemical,
• MeSH
• cytochrom P-450 CYP1A1 chemie   metabolismus   MeSH
• dexamethason chemie   farmakologie   MeSH
• diosmin chemie   farmakologie   MeSH
• flavanony chemie   farmakologie   MeSH
• indoly chemie   farmakologie   MeSH
• inhibitory enzymů chemie   farmakologie   MeSH
• jaterní mikrozomy účinky léků   enzymologie   MeSH
• játra účinky léků   enzymologie   MeSH
• kinetika MeSH
• klotrimazol chemie   farmakologie   MeSH
• Oncorhynchus mykiss metabolismus   MeSH
• quercetin chemie   farmakologie   MeSH
• rybí proteiny chemie   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• cytochrom P-450 CYP1A1 MeSH
• dexamethason MeSH
• diosmin MeSH
• flavanony MeSH
• indole-3-carbinol MeSH Prohlížeč
• indoly MeSH
• inhibitory enzymů MeSH
• klotrimazol MeSH
• naringenin MeSH Prohlížeč
• quercetin MeSH
• rybí proteiny MeSH

Flavonoids are known to have effects on cytochrome P450 enzymatic activity. However, little effort has been made to examine species differences and the relevance of studies on mammalian and fish microsomes so that extrapolations can be made to humans. Therefore, the effects of several naturally occurring flavonoids on the activity of CYP3A-dependent 7-benzyloxy-4-trifluoromethylcoumarin O-debenzylase (BFCOD) were evaluated in human, pig, mouse, and juvenile rainbow trout sources of hepatic microsomes. Each was exposed to three concentrations (1, 10, and 100μM) of diosmin, naringin, and naringenin. Naringenin competitively inhibited BFCOD activity (Ki values were 24.6μM in human, 15.6μM in pig, and 19.6μM in mouse microsomes). In fish, BFCOD activity was inhibited in a noncompetitive manner (Ki=7μM). Neither diosmin nor naringenin affected BFCOD activity in hepatic microsomes from the studied model organisms. These results suggest that dietary flavonoids potentially inhibit the metabolism of clinical drugs.

• Klíčová slova
• CYP3A, Diosmin, Diosmin (PubChem CID: 5353588), Inhibition, Naringenin, Naringenin (PubChem CID: 932), Naringin, Naringin (PubChem CID: 25075),
• MeSH
• Citrus chemie   MeSH
• cytochrom P-450 CYP3A genetika   metabolismus   MeSH
• diosmin farmakologie   MeSH
• druhová specificita MeSH
• exprese genu MeSH
• flavanony farmakologie   MeSH
• hydrolýza MeSH
• inhibitory enzymů farmakologie   MeSH
• jaterní mikrozomy účinky léků   enzymologie   MeSH
• játra účinky léků   enzymologie   MeSH
• kinetika MeSH
• kumariny metabolismus   MeSH
• lidé MeSH
• myši inbrední ICR MeSH
• myši MeSH
• Oncorhynchus mykiss MeSH
• prasata MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 7-benzyloxy-4-trifluoromethylcoumarin MeSH Prohlížeč
• cytochrom P-450 CYP3A MeSH
• diosmin MeSH
• flavanony MeSH
• inhibitory enzymů MeSH
• kumariny MeSH
• naringenin MeSH Prohlížeč
• naringin MeSH Prohlížeč

• MeSH
• bércové vředy farmakoterapie   MeSH
• diosmin terapeutické užití   MeSH
• hesperidin terapeutické užití   MeSH
• lidé MeSH
• lymfedém farmakoterapie   MeSH
• žilní insuficience farmakoterapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• komentáře MeSH
• úvodníky MeSH
• Názvy látek
• diosmin MeSH
• hesperidin MeSH

Chronic venous disorder (CVD) is a common illness with high incidence existing especially in Europe and North America. The main goal of micronized purified flavonoid fraction (MPFF) of diosmin and hesperidin is to eliminate the symptoms of CVD (venous pain, fatigue, etc). But MPFF of diosmin and hesperidin has good effectiveness for treatment of venous oedema and venous ulcer too. There are many papers that prove its effectiveness in the experiment and in the microcirculation too. The other indications for MPFF of diosmin hesperidin is hemorrhoidal disease and the accessory treatment of lymphedema. It is proved that this substance could be used as an effective supplementary treatment of symptoms after venous intervention. Only MPFF diosmin and hesperidin received the best recommendation - 1B in the last guidelines for VAD therapy.

• MeSH
• bércové vředy farmakoterapie   MeSH
• chronická nemoc MeSH
• diosmin terapeutické užití   MeSH
• hemoroidy farmakoterapie   MeSH
• hesperidin terapeutické užití   MeSH
• lidé MeSH
• lymfedém farmakoterapie   MeSH
• mikrocirkulace účinky léků   MeSH
• výsledek terapie MeSH
• žilní insuficience farmakoterapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Geografické názvy
• Evropa MeSH
• Názvy látek
• diosmin MeSH
• hesperidin MeSH

A nanofibrous membrane carrier for nearly water insoluble drug diosmin was formulated. The aim of this study was to evaluate the drug release and dissolution properties in an aqueous buffer of pH 7.8, and to compare the suitability of the drug carrier with the available drug forms and screen diosmin absorption extent. The membranes were produced from HPC/PVA/PEO-drug water solutions and then evaluated by SEM and DSC measurements. The results showed that diosmin was incorporated within the nanofibers in an amorphous state, and/or as a solid dispersion. The results of in vitro release experiments excerpt a very fast release of the drug, followed by the formation of an over saturated solution and partial precipitation of the drug (a "spring" effect). The enormous increases in dissolution of the drug from a nanofibrous carrier, compared to a micronized and crystalline form, was achieved. The in vivo bioavailability study carried out on rats showed higher initial drug plasma levels and higher AUC values after administration of the nanofibrous drug formulation, compared to the micronized form. The results of the study demonstrated that the improvement of the diosmin in vitro dissolution also brought the enhanced in vivo absorption extent of the drug.

• Klíčová slova
• Diosmin, Electrospinning, Nanofibre, Oral bioavailability, Solubility,
• MeSH
• aplikace orální MeSH
• diosmin aplikace a dávkování   krev   chemie   farmakokinetika   MeSH
• intestinální absorpce MeSH
• nanovlákna aplikace a dávkování   chemie   MeSH
• nosiče léků aplikace a dávkování   chemie   farmakokinetika   MeSH
• potkani Wistar MeSH
• příprava léků metody   MeSH
• rozpustnost MeSH
• roztoky MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• diosmin MeSH
• nosiče léků MeSH
• roztoky MeSH

The aim of this clinical study was to compare the degree of postoperative pain (VAS--10 cm, quality of life questionnaire CIVIQ and patient diary) between two groups of patients: patients treated with Detralex 14 days before and 14 days after the stripping of greater saphenous vein (GSV) and patients not treated with Detralex. In addition, the two groups were also compared for the incidence of symptoms associated with chronic venous insufficiency (CVI) (using the VAS scale: edema, tired and heavy legs, cramps, itching sensation), size of hematoma, use of analgesics and overall efficacy of the treatment. Clinical study included 181 patients from 15 medical centers throughout the Czech Republic. High ligation and partial stripping of greater saphenous vein on one lower extremity was performed in all patients (short stripping from groin to knee). Patients were randomly assigned in two groups: patients treated with Detralex (92) and patients not treated with Detralex (89). Patients in the first group were treated with Detralex for the period of 1 month. Degree of pain and patient's health condition were evaluated by the physician during D-14 (14 days prior to the surgery), D7 and D14 (7 and 14 days after the surgery) visits using the 10-cm visual analog scale VAS. The results indicate that Detralex reduced the intensity of postoperative pain, which resulted in decreased consumption of analgesics. Hematoma was smaller in patients already using Detralex 14 days prior to the scheduled stripping procedure. These patients also showed significant improvement of CVI symptoms and the quality of life of patients with CVI. High quality venoactive drugs administered 14 days prior to the surgery improve postoperative course in patients indicated for surgical treatment of varices.

• MeSH
• chronická nemoc MeSH
• diosmin terapeutické užití   MeSH
• dospělí MeSH
• fixní kombinace léků MeSH
• hesperidin terapeutické užití   MeSH
• kvalita života MeSH
• lidé středního věku MeSH
• lidé MeSH
• měření bolesti MeSH
• mladiství MeSH
• pooperační bolest prevence a kontrola   MeSH
• pooperační komplikace MeSH
• vena saphena chirurgie   MeSH
• výkony cévní chirurgie MeSH
• žilní insuficience chirurgie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• klinické zkoušky MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• diosmin MeSH
• fixní kombinace léků MeSH
• hesperidin MeSH
• S 5682 MeSH Prohlížeč