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Hydroxyethylrutosides

A Review of its Pharmacology, and Therapeutic Efficacy in Venous Insufficiency and Related Disorders

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Summary

Synopsis

Hydroxyethylrutosides is a standardised mixture of semisynthetic flavonoids, mainly mono-, di-, tri-, and tetrahydroxyethylrutosides, which acts primarily on the microvascular endothelium to reduce hyperpermeability and oedema. In patients with chronic venous insufficiency or diabetes, hydroxyethylrutosides improves microvascular perfusion and microcirculation, and reduces erythrocyte aggregation. The preparation also has a possible protective effect on the vascular endothelium.

In short to medium term placebo-controlled studies (up to 6 months) hydroxyethylrutosides therapy improved signs and symptoms of chronic venous insufficiency, including venous insufficiency associated with pregnancy and lymphoedema, and was well tolerated. However, the long term effects of hydroxyethylrutosides administration have yet to be demonstrated. The preparation also alleviated symptoms in patients with severe haemorrhoids, although there were no corresponding objective improvements. Hydroxyethylrutosides administration has been associated with reductions in retinal vascular permeability in patients with diabetic retinopathy but has no apparent effect on signs of retinal haemorrhage, although a reduction in oedema and haemorrhage has been reported in other patients receiving oral hydroxyethylrutosides in the acute phase of central retinal vein occlusion.

There are only limited effective pharmacological treatment options for patients with chronic venous insufficiency or lymphoedema, and hydroxyethylrutosides clearly improves signs and symptoms of these disorders. While its role in diabetic retinopathy and haemorrhoids requires some clarification, hydroxyethylrutosides therapy shows promise as a useful additional option for the management of oedema and other symptoms of chronic venous insufficiency.

Pharmacological Profile

Hydroxyethylrutosides is a standardised mixture of semisynthetic flavonoids, comprised mainly of mono-, di-, tri-, and tetrahydroxyethylrutosides. It acts mainly on the microvascular endothelium where it reduces hyperpermeability and oedema. In healthy volunteers, and patients with chronic venous insufficiency, lower limb oedema, idiopathic oedema or diabetic microangiopathy, single doses of hydroxyethylrutosides (0.3 to 1g orally or intravenously) reduce capillary filtration rate. In addition, oral dosages of 1 to 3g daily have improved parameters of microvascular perfusion, including transcutaneous partial oxygen pressure (pO2), and have reduced oedema formation in patients with chronic venous insufficiency. Oral and intravenous administration of 3 g/day decreases microvascular permeability in patients with severe venous hypertension and patients with diabetic microangiopathy.

Hydroxyethylrutosides inhibits erythrocyte aggregation in healthy volunteers and preserves erythrocyte deformability in patients undergoing cardiac valve replacement.

Hydroxyethylrutosides attenuates nicotine-induced endothelial cell damage in healthy volunteers, and in animals, it has inhibited free radical scavenging. The preparation also appears to have an affinity for vein walls with a possible protective effect against endothelial cell damage and hydroxyl radical formation.

There are limited data available on the pharmacokinetic properties of hydroxyethylrutosides in humans and none in special patient groups such as pregnant women, diabetics or elderly patients. Data from studies in healthy volunteers show that the proportion of a dose of hydroxyethylrutosides reaching the systemic circulation is low; about 10% of an orally administered dose is absorbed. In healthy volunteers peak plasma hydroxyethylrutosides concentrations are reached within 1 to 6 hours of oral administration. A maximum plasma concentration of 142 μg/L was reached following a single oral 900mg dose. The plasma elimination half-life ranges from 10 to 25 hours after oral administration and is approximately 1 hour after intravenous administration. The components undergo degradation by intestinal flora to aglycones, although mono-, di- and trihydroxyethylrutosides may undergo hepatic metabolism and are eliminated primarily via the bile. Three to 6% of an orally administered dose is excreted in the urine.

Therapeutic Efficacy

In patients with chronic venous insufficiency, hydroxyethylrutosides 0.6 to 1.2 g/day for up to 6 months significantly improves objective and subjective measures of lower limb venous insufficiency. In most placebo-controlled studies the improvements in leg volume, calf and/or ankle circumference, and relief from symptoms of pain, tired legs, night cramps, and restless legs achieved during hydroxyethylrutosides therapy were significantly greater than those reported during placebo therapy. The wearing of supportive elastic hosiery did not appear to affect response. Overall, 73 to 100% of patients had some improvement during hydroxyethylrutosides therapy and 25 to 90% responded to placebo treatment. Response rates (percentage of patients with improvements) for individual symptoms during hydroxyethylrutosides therapy ranged from 54 to 82% for pain, 35 to 55% for restless legs, 64 to 68% for tired ‘heavy’ legs and 59 to 91% for cramps. Improvements in signs and symptoms of venous insufficiency (including cramps, irritation, swelling and pain) and reductions in accumulation of extravascular fluid correlated with improvements in microcirculatory parameters. Reductions in ankle circumference, and improvements in symptoms of pain, night cramps and paraesthesia were achieved in patients with varicosis of pregnancy treated with hydroxyethylrutosides 0.3 to 1.8 g/day. However, effects on the healing rate of leg ulcers have been equivocal.

Signs and symptoms of haemorrhoids, including haemorrhoids of pregnancy, have been improved by oral therapy with hydroxyethylrutosides (0.6 to 2g daily for up to 3 to 4 weeks), although in most studies the response of hydroxyethylrutosides-treated patients was significantly greater than that of placebo recipients only in patients with severe symptoms, and objective measures of haemorrhoid severity were not altered. Signs and symptoms of lymphoedema have been alleviated by hydroxyethylrutosides treatment (3 g/day for 6 months), and radiotherapyinduced damage to skin and/or mucosa has also been reduced using concomitant hydroxyethylrutosides therapy (0.6 to 2g daily). In addition, hydroxyethylrutosides has reduced foot swelling rates and reduced retinal vascular permeability of patients with diabetic microangiopathy and retinopathy, respectively, although it does not appear to have any effect on existing retinal haemorrhage in these patients. However, oedema and haemorrhage were reduced in patients receiving oral hydroxyethylrutosides early in the acute phase of central retinal vein occlusion.

Clinical Tolerability

Administration of hydroxyethylrutosides in clinical trials has generally been well tolerated. The incidence of adverse events reported by patients receiving treatment with hydroxyethylrutosides was similar to that reported by placebo recipients. Gastrointestinal disturbances, headache, dizziness and/or pruritus were the effects most frequently associated with either active or placebo therapy in most studies of patients with chronic venous insufficiency. In studies of patients with haemorrhoids, gastrointestinal disturbances were the most frequently reported adverse events. Hydroxyethylrutosides had no effect on glycaemic control in patients with diabetes.

Dosage and Administration

The recommended hydroxyethylrutosides dosage is 0.9 to 1.2 g/day orally, for patients with venous insufficiency and those with haemorrhoids, and 3g/day orally, for patients with lymphoedema. A dosage of 1.2 to 2.4g daily has been used in patients with diabetic retinopathy and dosages of 0.6 to 2 g/day have been administered to patients with skin and/or mucosal damage associated with radiotherapy. Hydroxyethylrutosides should not be administered during the first 3 months of pregnancy.

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References

  • Agolini G, Cavallini GM. Treatment of long term retinal vasculopathies with high oral dosages of O-(beta-hydroxyethyl)-rutosides. Clinica Therapeutica 120: 101–110, Jan 1987

    CAS  Google Scholar 

  • Allen A, Tooke JE. Effects of hydroxyethyl-rutosides in diabetes mellitus. Phlebology 5 (Suppl. 1): 27–31, 1990

    Google Scholar 

  • Anderson JH, Geraghty JG, Wilson YT, Murray GD, McArdle CS, et al. Paroven and graduated compression hosiery for superficial venous insufficiency. Phlebology 5: 271–276, 1990

    Google Scholar 

  • Annoni F, Boccasanta P, Chiurazzi D, Mozzi E, Oberhauser V. Treatment of acute symptoms of haemorrhoidal disease with high dose oral O-(β-hydroxyethyl)-rutoside. Minerva Medica 77: 1663–1668, 1986

    PubMed  CAS  Google Scholar 

  • Arturson G. Effects of O-(β-hydroxyethyl)-rutosides (HR) on the increased microvascular permeability in experimental skin burns. Acta Chirurgica Scandinavica 138: 111–117, 1972

    PubMed  CAS  Google Scholar 

  • Arturson G, Jonsson C-E. Effects of O-(β-hydroxyethyl)-rutosides (HR) and indomethacin on transcapillary macromolecular transport and prostaglandins following scalding injury. Bibliotheca Anatomica 12: 465–470, 1973

    PubMed  CAS  Google Scholar 

  • Balant LP, Wermeille M, Griffiths LA. Metabolism and pharmacokinetics of hydroxyethylated rutosides in animals and man. Drug Metabolism and Drug Interactions 5: 1–23, 1984

    Article  PubMed  CAS  Google Scholar 

  • Balmer A, Limoni C. A double-blind placebo-controlled clinical trial of Venoruton® on the symptoms and signs of chronic venous insufficiency. The importance of patient selection. VASA — Journal for Vascular Diseases 9: 76–82, 1980

    CAS  Google Scholar 

  • Barrow A, Griffiths LA. Metabolism of the hydroxyethylrutosides II. Excretion and metabolism of 3′4′7-tri-O-(β-hydroxyethyl)rutoside and related compounds in laboratory animals after parenteral administration. Xenobiotica 4: 1–16, 1974a

    CAS  Google Scholar 

  • Bast A, Jansen FP, Haenen GRMM. Free radical scavenging activity of hydroxyethylrutosides. Abstract. 17th European Conference on Microcirculation, London, July 5–10, 1992

  • Beier A. Therapeutic prevention and treatment of venous disorders during pregnancy. Zeitschrift für Therapie 8: 481–485, 1967

    Google Scholar 

  • Belcaro G, D’Aulerio A, Rulo A, Candiani C. Evaluation of capillary permeability and microcirculation in patients with chronic venous hypertension treated with Venoruton by the vacuum suction chamber (VSC) device and Laser-Doppler flowmetry. Phlébologie 41: 847–856, 1988

    PubMed  CAS  Google Scholar 

  • Belcaro G, Rulo A, Candiani C. Evaluation of the microcirculatory effects of Venoruton in patients with chronic venous hypertension by Laserdoppler flowmetry, transcutaneous pO2 and PCO2 measurements, leg volumetry and ambulatory venous pressure measurements. VASA — Journal for Vascular Diseases 18: 146–151, 1989

    CAS  Google Scholar 

  • Belcaro G, Candiani C. Chronic effects of O-(β-hydroxyethyl)-rutosides on microcirculation and capillary filtration in diabetic microangiopathy. Current Therapeutic Research 49: 131–139, 1991

    Google Scholar 

  • Bergqvist D, Hallböök T, Lindblad B, Lindhagen A. A double-blind trial of O-(β-hydroxyethyl)-rutoside in patients with chronic venous insufficiency. VASA — Journal for Vascular Diseases 10: 253–260, 1981

    CAS  Google Scholar 

  • Bergstein NAM. Clinical study on the efficacy of O-(β-hydroxyethyl)rutoside (HR) in varicosis of pregnancy. Journal of International Medical Research 3: 189–193, 1975

    PubMed  CAS  Google Scholar 

  • Blumberg S, Clough G, Michel C. Effects of hydroxyethyl rutosides upon the permeability of single capillaries in the frog mesentery. British Journal of Pharmacology 96: 913–919, 1989

    Article  PubMed  CAS  Google Scholar 

  • Bollinger A, Isenring G, Franzeck UK. Lymphatic microangiopathy: a complication of severe chronic venous incompetence (CVI). Lymphology 15: 60–65, Jun 1982

    PubMed  CAS  Google Scholar 

  • Börcsök E, Földi K, Györi I, Zoltán: OT, Földi M. Treatment of experimental lymphoedema with the semi-synthetic bioflavonoid O-(β-Hydroxyethyl)-rutosides(HR). Angiologica 7: 51–52, 1970

    PubMed  Google Scholar 

  • Braun HD, Becker T, Meyer U. Behandlung von Stauungserscheinungen nach Ablatio Mammae und Bestrahlung. Munchener Medizinische Wochenschrift 113: 1630–1633, 1971

    PubMed  CAS  Google Scholar 

  • Broks PDC. Effect of O-(β-hydroxyethyl)-rutoside in lymphangiography. American Journal of Roentgenology 128: 263–265, 1977

    PubMed  CAS  Google Scholar 

  • Browse NL, Burnand KG. The cause of venous ulceration. Lancet 2: 243–245, 1982

    Article  PubMed  CAS  Google Scholar 

  • Burnand KG, Powell S, Bishop C, Stacey M, Pulvertaft T. Effect of Paroven on skin oxygenation in patients with varicose veins. Phlebology 4: 15–22, 1989

    Google Scholar 

  • Burnand KG, Whimster I, Naidoo A, Browse NL. Pericapillary fibrin in the ulcer-bearing skin of the leg: the cause of lipodermatosclerosis and venous ulceration. British Medical Journal 285: 1071–1072, 1982

    Article  PubMed  CAS  Google Scholar 

  • Callam MJ, Ruckley CV, Dale JJ, Harper DR. Hazards of compression treatment of the leg: an estimate from Scottish surgeons. British Medical Journal 295: 1382–1383, 1987

    Article  PubMed  CAS  Google Scholar 

  • Cappelli R, Pecchi S, Oberhauser V, Forconi S, di Perri T. Efficacy of O-(β-hydroxyethyl)-rutosides at high dosage in counteracting the unwanted activity of oral contraceptives on venous function. International Journal of Clinical Pharmacology Research 7: 291–299, 1987

    PubMed  CAS  Google Scholar 

  • Casley-Smith JR, Casley-Smith JR. High-protein oedemas and the benzo-pyrones. J.B. Lippencott Company, Sydney, 1986

    Google Scholar 

  • Casley-Smith JR, Casley-Smith JR. The effects of O-(β-hydroxyethyl)-rutosides (HR) on acute lymphoedema in rats’ thighs, with and without macrophages. Microcirculation Endothelium and Lymphatics 6: 457–463, 1990

    CAS  Google Scholar 

  • Cesarone MR, Laurora G, Ricci A, Belcaro G, Pomante P, et al. Acute effects of hydroxyethylrutosides on capillary filtration in normal volunteers, patients with venous hypertension and in patients with diabetic microangiopathy (a dose comparison study). Vasa — Journal of Vascular Diseases 21: 76–80, 1992

    CAS  Google Scholar 

  • Chant ADB. The effect of Paroven (HR) on the clearance of sodium-24 from the subcutaneous tissues of the foot in patients with varicose veins. VASA — Journal for Vascular Diseases 2: 288–291, 1973

    CAS  Google Scholar 

  • Chollet D, Arnera V, Meyer P, Llull JB, Wermeille M. Biliary excretion of O-(β-hydroxyethyl)-rutosides in man after oral intake. Abstract No. 258. European Journal of Drug Metabolism and Pharmacokinetics 15 (Suppl.): 37, 1990

    Article  Google Scholar 

  • Clyne MB, Freeling P, Ginsborg S. Troxerutin in the treatment of haemorrhoids. Practitioner 198: 430–433, 1967

    Google Scholar 

  • Coleridge Smith PD, Thomas P, Scurr JH, Dormandy JA. Causes of venous ulceration: a new hypothesis. British Medical Journal 296: 1726–1727, 1988

    Article  PubMed  CAS  Google Scholar 

  • Cuendet JF, Sévin R. Diabetic retinopathies: possibilities and limitations of treatment with high doses of a P factor, O-β-(hydroxyethyl)-rutosides. Ophthalmologica 148: 121–129, 1964

    Article  PubMed  CAS  Google Scholar 

  • de Jongste AB, Jonker JJC, Huisman MV, ten Cate JW, Azar AJ. A double blind three center clinical trial on the short-term efficacy of O-(β-hydroxyethyl)-rutosides in patients with postthrombotic syndrome. Thrombosis and Haemostasis 62: 826–829, 1989

    PubMed  Google Scholar 

  • Dittrich P, Ostrowski J, Beubler E, Schraven E, Kukovetz W. HPLC-Bestimmung von Troxerutin im Plasma und Harn nach oraler Gabe am Menschen. Arzneimittel-Forschung/Drug Research 35: 765–767, 1985

    CAS  Google Scholar 

  • Eastham RD, Perham TGM, Pocock PV. Warfarin and hydroxyethylrutosides in deep vein thrombosis. British Medical Journal 4: 491, 1972

    Article  PubMed  CAS  Google Scholar 

  • Ekestrom S, Welti R. The affinity of hydroxyethyl-rutosides for the venous wall and its efficacy in preventing early occlusions of aorto-coronary vein bypass grafts. Phlebology 4 (Suppl. 1): 41–48, 1990

    Google Scholar 

  • Fagrell B. Local microcirculation in chronic venous incompetence and leg ulcers. Vascular Surgery 13: 217–225, 1979

    Article  Google Scholar 

  • Forconi S, Guerrini M, Perri TDI. Study of the activity of a flavonoid, O-(beta-hydroxyethyl)-rutoside, at high dose levels on venous tone measured by, strain gauge, plethysmography. VASA — Journal for Vascular Diseases 6: 279–284, 1977

    CAS  Google Scholar 

  • Förster H, Harth P, Hoos I. Studies on the absorption and metabolism of rutosides. Abstract. International Journal of Clinical Pharmacology 10: 139, 1974

    Google Scholar 

  • Freyler H, Haydn M. The use of O-β-hydroxyethyl-rutoside to reduce vascular permeability in diabetic retinopathy. Klinische Monatsblatter fur Augenheilkunde 160: 527–533, 1972

    PubMed  CAS  Google Scholar 

  • Gábor M. The effect of O-(β-hydroxyethyl)-rutosides (HR) on the skin capillary resistance of rats. Arzneimittel-Forschung/Drug Research 31: 442–445, 1981

    Google Scholar 

  • General Practitioner Research Group. An oral treatment for haemorrhoids. Practitioner 201: 378–381, 1968

    Google Scholar 

  • Gerdin B, Svensjö E. Inhibitory effect of the flavonoid O-(β-hydroxyethyl)-rutosides on increased microvascular permeability induced by various agents in rat skin. International Journal of Microcirculation — Clinical and Experimental 2: 39–46, 1983

    CAS  Google Scholar 

  • Griffiths LA, Barrow A. The fate of orally and parenterally administered flavonoids in the mammal. The significance of biliary excretion. Angiologica 9: 162–174, 1972

    CAS  Google Scholar 

  • Halborg-Sorensen AH, Hansen H. Chronic venous insufficiency treated with hydroxyethylrutoside (HR). Angiologica 7: 187–192, 1970

    Google Scholar 

  • Hammersen F. The ultrastructural charges in the microcirculation in experimental oedema: a suitable morphological testmodel for the effect of vaso-active drugs. Biorheology 6: 345–346, 1970

    Google Scholar 

  • Hackett AM, Griffiths LA, Luyckx AS, van Cauwenberge H. Metabolism of hydroxyethylrutosides (HR). Metabolism of [14 C]-HR in man. Arzneimittel-Forschung/Drug Research 26: 925–928, 1976

    CAS  Google Scholar 

  • Hackett AM, Griffiths LA. The metabolism and excretion of 7-mono-O-(β-hydroxyethyl) rutoside in the dog. European Journal of Drug Metabolism and Pharmacokinetics 4: 207–212, 1979

    Article  PubMed  CAS  Google Scholar 

  • Hilton JG. Effects of β-hydroxyethyl rutosides (H-R) administered post burn after thermal-injury-induced plasma volume loss in the nonresuscitated dog. Burns 8: 391–394, 1982

    Article  CAS  Google Scholar 

  • Hladovec J. Endothelial injury by nicotine and its prevention. Experientia 34: 1585–1586, 1978

    Article  PubMed  CAS  Google Scholar 

  • Jung G, Ottnad M, Voelter W. Quantitative determination of O-(β-hydroxyethyl)-rutosides in human blood after intravenous and oral administration by circular dichroism. European Journal of Drug Metabolism and Pharmacokinetics 2: 131–141, 1977

    Article  CAS  Google Scholar 

  • Kendall S, Towart R, Michel CC. Permeability reducing properties of O-(β-hydroxyethyl)-rutosides (Venoruton®) and its constituents. Abstract. 17th European Conference on Microcirculation, London, July 5–10, 1992

  • Klemm J. Contribution to the treatment of reactions in the skin and mucous membranes caused by partial high energy irradiation of the body. Strahlentherapie 125: 536–547, 1964

    PubMed  CAS  Google Scholar 

  • Kuhnz W, Zech K, Lupp R, Jung G, Voelter W. Quantitative determination of O-(β-hydroxyethyl)-rutosides in serum by highperformance liquid chromatography. Journal of Chromatography 272: 333–340, 1983

    Article  PubMed  CAS  Google Scholar 

  • Liu WL, Pearce FL, Towart R. Effect of O-(β-hydroxyethyl)-rutosides (Venoruton®) and its constituents on histamine secretion from isolated rat peritoneal mast cells. Abstract. 17th European Conference on Microcirculation, London, July 5–10, 1992

  • Lund F. Effect of i.v. hydroxyethylrutosides (HR) on the regional perfusion pattern in fluorescein angiography of seriously ischemic feet. Abstract. 1st Mediterranean Congress of Angiology, Corfu, p 140, May 29–Jun 3, 1988

  • Lund F. Fluoreszeinangiographische Studien Uber die Einwirkung intravenöser Venoruton-Behandlung auf die mikrovaskuläre Blutperfusion der Haut bei schweren Fällen von arteriellen GliedmassenverschlUssen. In Voelter & Jung (Eds). O-(beta-Hydroxyethyl)-rutoside. Neue Ergebnisse in Experiment und Klinik. Springer Verlag, Berlin-Heidelberg-New York, pp. 195–211,1983

    Google Scholar 

  • Lund F. Unexpected limb salvage by i.v. hydroxyethylrutosides (HR) and long term oral anticoagulation in 11 cases of critically leg ischaemia already decided for amputation. Abstract 239. 2nd Mediterranean Congress of Angiology, Antalya, 21–24 Sep, 1990

  • Lund F, Cronestrand R, Sonnenfeld T. Troxerutin in Raynaud’s syndrome. British Medical Journal 280: 334–335, 1980

    Article  PubMed  CAS  Google Scholar 

  • Lund F, Enoksson P, Mannerfelt T. A report on the treatment of acute central retinal vein occlusion with oral hydroxyethylrutosides. In Pulvertaft et al. (Eds) Hydroxyethylrutosides in Vascular Disease. International Congress and Symposium Series 42: 51–54, 1981

    Google Scholar 

  • Lund F, Fagrell B, Kunichi J, Glenne PO. The effect of O-(beta-hydroxyethyl)-rutosides in postischaemic and stasis oedema of the rat tail. Studied by means of a simple displacement technique for volume measurement. In van der Molen et al. (Eds). Progrès Cliniques et Thérapeutiques dans le Domaine de la Phlébologie,Amsterdam 1968; Stenvert & Zoom, Apeldoorn, pp. 519–527, 1970

    Google Scholar 

  • Lund F, Gottlieb I, Inacio J. Evaluation of microvascular permeability by dermofluorography (DFG) from a finger in diabetics and non-diabetics: with a preliminary study on the effect of hydroxyethyl-rutosides (HR). Phlebology 5 (Suppl. 1): 33–40, 1990

    Google Scholar 

  • Mann RJ. A double blind trial of oral O(β-hydroxyethyl)-ruto-sides for stasis leg ulcers. The British Journal of Clinical Practice 35: 79–81, 1981

    PubMed  CAS  Google Scholar 

  • McEwan AJ, McArdle CS. Effect of hydroxyethylrutosides on blood oxygen levels and venous insufficiency symptoms in varicose veins. British Medical Journal 2: 138–141, 1971

    Article  PubMed  CAS  Google Scholar 

  • Michel C, Blumberg S, Clough G. Hydroxyethyl-rutosides (HR) reduce permeability of frog mesenteric microvessels. Phlebology 5 (Suppl. 1): 3–7, 1990

    Google Scholar 

  • Michel CC, Kendall S. O-(β-hydroxyethyl)-rutosides (HR) reduce the hydraulic permeability of microvessels perfused with protein free solutions. Abstract. 17th European Conference on Microcirculation, London, July 5–10, 1992

  • Müller B, Nocker W, Diebschlag W. Clinical trials of the doserelated effects of O-(β-hydroxyethyl)-rutosides in patients with chronic venous insufficiency. 5th European-American Symposium on Venous Diseases. Vienna, 7–10 Nov 1990

  • Nees S. O-(β-hydroxyethyl)-rutosides (HR) protect vascular endothelium against oxidative injury. Abstract. 17th European Conference on Microcirculation, London, July 5–10, 1992

  • Neumann HAM, Carlsson K, Brom GHM. The uptake and localisation of O-(β-hydroxyethyl)-rutosides in the venous wall, measured by laser scanning microscopy. European Journal of Clinical Pharmacology: in press, 1992

  • Neumann HAM, van den Broek MJTB. Evaluation of O-(β-hydroxyethyl)-rutosides in chronic venous insufficiency by means of non-invasive techniques. Phlebology 5 (Suppl. 1): 13–20, 1990

    Google Scholar 

  • Nocker W, Diebschlag W. An investigation of dosage effects with drinking solutions of O-(beta-hydroxyethyl)-rutosides. VASA — Journal for Vascular Diseases 16: 365–369, 1987

    CAS  Google Scholar 

  • Nocker W, Diebschlag W, Lehmacher W. Three-month randomised, double-blind dose-response study with O-(beta-hydroxyethyl)-rutosides drinking solution. VASA — Journal for Vascular Diseases 18: 235–238, 1989

    CAS  Google Scholar 

  • Pearson JD, Carleton JS, Beesley JE, Hutchings A, Gordon JL. Granulocyte adhesion to endothelium in culture. Journal of Cell Science 38: 225–235, 1979

    PubMed  CAS  Google Scholar 

  • Piller NB. macrophage and tissue changes in the developmental phases of secondary lymphoedema and during conservative therapy with benzopyrone. Archives of Histology and Cytology 53 (Suppl.): 209–218, 1990

    Article  PubMed  Google Scholar 

  • Piller NB, Morgan RG, Casley-Smith JR. A double-blind, crossover trial of O-(β-hydroxyethyl)-rutosides (benzo-pyrones) in the treatment of lymphoedema of the arms and legs. British Journal of Plastic Surgery 41: 20–27, 1988

    Article  PubMed  CAS  Google Scholar 

  • Pferovsky I, Roztocil K, Hlavová A, Koleilat Z, Rázgová L, et al. The effect of hydroxyethylrutosides after acute and chronic oral administration in patients with venous diseases. A double-blind study. Angiologica 9: 408–414, 1972

    Google Scholar 

  • Pferovsky I, Hladovec J. Suppression of the desquamating effect of smoking on the human endothelium by hydroxyethylrutosides. Blood Vessels 16: 239–240, 1979

    Google Scholar 

  • Pulvertaft TB. Paroven in the treatment of chronic venous insufficiency. Practitioner 223: 838–841, 1979

    PubMed  CAS  Google Scholar 

  • Pulvertaft TB. General practice treatment of symptoms of venous insufficiency with oxerutins. Results of a 660 patient multicentre study in the UK. VASA — Journal for Vascular Diseases 12: 373–376, 1983

    CAS  Google Scholar 

  • Quigley FG, Faris IB. A study on the effect of hydroxyethylrutoside on transcutaneous oxygen tension measurements in patients with severe venous insufficiency. Vascular Surgery 25: 42–47, 1991

    Article  Google Scholar 

  • Rázgová L, Roztocil K, Hálová J, Fischer A. The effect of O-(β-hydroxyl)-rutosides (HR) on peripheral blood vessels of the lower extremities in idiopathic oedema. European Journal of Clinical Pharmacology 3: 247–251, 1971

    Article  PubMed  Google Scholar 

  • Rehn D, Hennings G, Nocker W, Diebschlag W. Time course of the anti-oedematous effect of O-(β-hydroxyethyl)-rutosides in healthy volunteers. European Journal of Clinical Pharmacology 40: 625–627, 1991

    PubMed  CAS  Google Scholar 

  • Rekka E, Kourounakis PN. Effect of hydroxyethyl rutosides and related compounds on lipid peroxidation and free radical scavenging activity. Some structural aspects. Journal of Pharmacy and Pharmacology 43: 486–491, 1991

    CAS  Google Scholar 

  • Roztocil K, Fischer A, Novák P, Rázgová L. The effect of O-(β-hydroxyethyl)-rutosides (HR) on the peripheral circulation in patients with chronic venous insufficiency. European Journal of Clinical Pharmacology 3: 243–246, 1971

    Article  PubMed  CAS  Google Scholar 

  • Roztocil K, Pferovsky I, Oliva I. The effect of hydroxyethylrutosides on capillary filtration rate in the lower limb of man. European Journal of Clinical Pharmacology 11: 435–438, 1977

    Article  PubMed  CAS  Google Scholar 

  • Samartzis S, Hauser GA. Incidence and treatment of pain in legs and veins during pregnancy. Therapeutische Umschau / Revue Thérapeutique 28: 485–489, 1971

    CAS  Google Scholar 

  • Schmid W. Varicose veins in pregnancy. Medical prophylaxis and treatment. Fortschritte der Medizin 90: 1273–1280, 1972

    Google Scholar 

  • Schmid-Schönbein H, Volger E, Weiss J, Brandhuber M. Effects of O-(β-hydroxyethyl)-rutosides on the microrheology of human blood under defined flow conditions. VASA — Journal for Vascular Diseases 4: 263–270, 1975

    Google Scholar 

  • Schultz-Ehrenburg U, Müller B. Two clinical trials of two different dosages of O-(β-hydroxyethyl)-rutosides in the treatment of venous ulcers. Abstract. 17th European Conference on Microcirculation, London, July 5–10, 1992

  • Sinnatamby CS. The treatment of haemorrhoids. Role of hydroxyethylrutosides, troxerutin (Paroven; Varemoid; Venoruton). Clinical Trials Journal 10: 45–51, 1973

    Google Scholar 

  • Sonnenfeld T, Ekeström S, Lal Koul B. Hydroxyethylrutosides during extracorporeal circulation: effect on erythrocyte deformability. Scandinavian Journal of Thoracic and Cardiovascular Surgery 19: 85–87, 1985

    Article  PubMed  CAS  Google Scholar 

  • Stegmann W, Hübner K, Deichmann B, Müller B. Efficacy of O-(β-hydroxyethyl)-rutosides in the treatment of venous varicose ulcer. Therapiewoche 36: 1828–1833, 1986

    Google Scholar 

  • Stemmer R, Furderer CR. Posologie de l’O-beta hydroxyéthylrutoside dans l’insuffisance veineuse chronique. Phlebologie 39: 995–1003, 1986

    PubMed  CAS  Google Scholar 

  • StrandnessJr. DE. Vascular diseases of the extremities. In Braunwald E, et al. (Eds) Harrison’s Principles of Internal Medicine, 11th ed. pp. 1040–1046, McGraw-Hill Book Company, New York, 1987

    Google Scholar 

  • Struckmann J. A review of some non-invasive, volumetric, diagnostic techniques in patients with CVI. Phlebology (Suppl. 1); 9-12, 1990

  • Svensjö E, Arfors K-E, Arturson G. Effect of inhibition of PGE2 -activity on FITC-dextran permeability in the hamster microvasculature. Bibliotheca Anatomica No. 13, pp. 303-304, 1975

  • Szepesi S, Müller B, Jacobi V, Klima A, Bettinger W, et al. Prophylaxis of radiation-induced mucosal reactions in patients with tumours of the head and neck. Results of a randomised study of Venoruton-intens versus and untreated control group. In Felix W (Ed) O-(β-hydroxyethyl)-rutoside, Neue Ergebnisse aus Klinik und Forschung, pp 44–54, Springer-Verlag, Berlin 1987

    Google Scholar 

  • Taylor HM, Twycross RG. The use of hydroxyethylrutosides in post-mastectomy lymphoedema. Abstract. 17th European Conference on Microcirculation, London, July 5–10, 1992

  • ten Cate JW, van Haeringen NJ, Gerritsen J, Glasius E. Biological activity of a semisynthetic flavonoid, O-(β-hydroxyethyl)rutoside: light-scattering and metabolic studies of human red cells and platelets. Clinical Chemistry 19: 31–35, 1973

    PubMed  Google Scholar 

  • Thomas PRS, Nash GB, Dormandy JA. White cell accumulation in dependent legs of patients with venous hypertension: a possible mechanism for trophic changes in the skin. British Medical Journal 296: 1693–1695, 1988

    Article  PubMed  CAS  Google Scholar 

  • Thorp RH, Hughes ESR. A clinical trial oftrihydroxyethylrutoside (’Varemoid’) in the treatment of haemorrhoids. Medical Journal of Australia: 1076-1078, 1970

  • Timeus C. The effect of oral O-(β-hydroxyethyl)-rutoside (HR) versus placebo on vessel wall permeability and selective permeability in the microcirculation of the skin in healthy volunteers. In Negus E et al. (Eds) Phlebology 85, pp 825-827, J. Libbey & Co Ltd. 1986

  • Tschopp M, Pometta D, Babel J. Diabetic retinopathy: study of the action of O-beta-hydroxyethyl-rutosides (HR) by retinal fluoresceinography. Diabetologia 6: 475–481, 1970

    Article  PubMed  CAS  Google Scholar 

  • van Acker SABE, Towart R, Hüsken BCP, de Jong J, van der Vijgh WJF, et al. The protective effect of Venoruton and its main constituents on acute doxorubicin-induced cardiotoxicity. Abstract. 17th European Conference on Microcirculation, London, July 5–10, 1992

  • van Cauwenberge H. Double blind study of the efficacy of O-(β-hydroxyethyl)-rutosides in the treatment of venous conditions. Médecine et Hygiène 36: 4175–4177, 1978

    Google Scholar 

  • Van Haeringen NJ, Glasius E, ten Cate JW, Gerritsen J, van Geet J. Effect of O-(β-hydroxyethyl)-rutoside on red cell and platelet functions in man. Bibliotheca Anatomica 12: 459–464 1973

    PubMed  Google Scholar 

  • Vicari S, Babel J, Cardinet J. The action of trihydroxyethylrutoside in diabetic retinopathy. Ophthalmologica 154: 21–30, 1967

    Article  PubMed  CAS  Google Scholar 

  • Wienert V, Gahlen W. Excretion of tri-hydroxyethyl rutoside (Venoruton®) by the kidney after parenteral and oral administration. Hautarzt 21: 278–279, 1970

    PubMed  CAS  Google Scholar 

  • Wenner A, Leu HJ, Spycher M, Brunner U. Ultrastructural changes of capillaries in chronic venous insufficiency. Experimental Cell Biology 48: 1–14, 1980

    Google Scholar 

  • Wijayanegara H, Mose JC, Achmad L, Sobarna R, Permadi W. A clinical trial of hydroxyethylrutosides in the treatment of haemorrhoids of pregnancy. Journal of International Medical Research 20: 54–60, 1992

    PubMed  CAS  Google Scholar 

  • Wild C, Fasel J. Effect of a flavonoid on the capillary resistance of the rectal mucosa in hepatic cirrhosis. American Journal of Proctology 20: 60–62, 1969

    PubMed  CAS  Google Scholar 

  • Wiratmahusada L, Soewito B, Riwanto I. A double blind clinical trial of O-(β-hydroxyethyl)-rutosides (HR) in the treatment of symptoms related to haemorrhoids. Medika 9: 531–533, 1980

    Google Scholar 

  • Wright DDI, Franks PJ, Blair SD, Backhouse CM, Moffat C, et al. Oxerutins in the prevention of recurrence in chronic venous ulceration: randomized controlled trial. British Journal of Surgery 78: 1269–1270, 1991

    Article  PubMed  CAS  Google Scholar 

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  1. Adis International Limited, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, Auckland 10, New Zealand

    Alison N. Wadworth & Diana Faulds

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  1. Alison N. Wadworth
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  2. Diana Faulds
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Various sections of the manuscript reviewed by: A. Auteri, Institute of Internal Medicine, Division of Immunology, University of Siena, Policlinico ‘Le Scotte’ Siena, Italy; J.R. Casley-Smith, Henry Thomas Laboratory (Microcirculation Research), University of Adelaide, Adelaide, South Australia, Australia; A.B. de Jongste, Department of Surgery, Rode Kruis Ziekenhuis, Den Haag, The Netherlands; F. Lund, Microcirculation Laboratory, Department of Clinical Physiology, Södersjukhuset, Stockholm, Sweden; N.B. Piller, Flinders University of South Australia, Adelaide, South Australia, Australia; D.D.I. Wright, Department of Surgery, Charing Cross Hospital, Charing Cross and Westminster Medical School, London, England.

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Wadworth, A.N., Faulds, D. Hydroxyethylrutosides. Drugs 44, 1013–1032 (1992). https://doi.org/10.2165/00003495-199244060-00009

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