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Ticrynafen: A Novel Uricosuric Antihypertensive Natriuretic Agent

Ticrynafen: A Novel Uricosuric Antihypertensive Natriuretic Agent Abstract Interest in new diuretics with less side effects has led to the synthesis of ticrynafen, an uricosuric diuretic. This agent was compared with hydrochlorothiazide in a crossover design study involving 12 hypertensive men. Both agents significantly decreased mean arterial pressure from 8% to 18% in eight of the 12 patients. In addition to reducing body weight, these diuretics induced reversible changes in BUN and carbon dioxide content (increased) and plasma concentration of potassium and chloride ions (decreased). The most important change in renal function was a 2.5-fold increase in fractional urate clearance by ticrynafen associated with reduction of serum uric acid by 62%. Thus, ticrynafen is a promising therapeutic agent in hypertension, adding a unique uricosuric effect that should improve patient compliance. (Arch Intern Med 138:53-57, 1978) References 1. Thuillier G, Laforest J, Caribou B, et al: Heterocyclin derivatives of phenoxyacetic acids, synthesis and preliminary study of their diuretic and uricosuric activities . Eur J Med Chem 9:625-633, 1974. 2. Stote RM, Cherrill DA, Erb BB, et al: Site of action of SKF 62698, a new diuretic-uricosuric agent . Clin Res 22:721A, 1974. 3. Lau K, Goldberg M, Stote R, et al: Renal effects of SKF 62698 (SKF): A new uricosuric agent . Clin Res 24:405A, 1976. 4. Stote RM, Cherril DA, Maass AR, et al: SKF 62698 (ANP3624): A diuretic with significant uricosuric activity . Sixth International Congress of Nephrology, Florence, Italy, June 5-12, 1975 , abstract 827. 5. Steele TH, Prasad DR, Reese OG: Pharmacogenesis of diuretic-induced hypouricemia , abstracted. Clin Pharmacol Ther 19:116, 1976. 6. Reese OG, Steele TH: Renal transport of urate during diuretic induced hypouricemia . Am J Med 60:973-979, 1976.Crossref 7. Masberbard A, Giudicelli C: Etude clinique de l'action antihypertensive de l'acide chloro-2,3-(thienyl-2-ceto)-phenoxyacetique en administration prolongee . Lyon Med 232:165-174, 1974. 8. Masbernard A, Giudicelli CP, Kamaludin T: Étude pharmacologique clinique de l'acide dichloro-2,3-(thienyl-c-ceto)-phenoxyacetique . J Pharmacol Clin 1976, spécial, 13-18. 9. Wood GA, Levitt SH: Simultaneous red cell mass and plasma volume determinations using 51Cr tagged red cells and 125I labeled albumin . J Nucl Med 6:433-440, 1965. 10. Smith HW, Finkelstein N, Aliminosa L, et al: The renal clearances of substituted hippuric acid derivatives and other aromatic acids in dog and man . J Clin Invest 24:388-404, 1945.Crossref 11. Tarazi RC, Dustan HP, Frohlich ED, et al: Plasma volume and chronic hypertension: Relationship to arterial pressure levels in different hypertensive diseases . Arch Intern Med 125:835-842, 1970.Crossref 12. Gifford RW Jr: Chlorothiazide in the treatment of hypertension . Postgrad Med 25:559-571, 1959. 13. Fallis NE, Ford RV: Current concepts in therapy: Limitations in the use of thiazide diuretics . N Engl J Med 263:504-505, 1960.Crossref 14. Maldonado MN, Eknoyan G, Suki WM: Diuretics in nonedematous states: Physiological basis for the clinical use . Arch Intern Med 131:797-808, 1973.Crossref 15. Paloyan E, Forland M, Pickleman JR: Hyperparathyroidism coexisting with hypertension and prolonged thiazide administration . JAMA 210:1243-1245, 1969.Crossref 16. Healey LA, Magid GJ, Decker JL: Uric acid retention due to hydrochlorothiazide . N Engl J Med 261:1358-1362, 1959.Crossref 17. Duarte C, Dreifus LS, Kodama R, et al: Pattern of uric acid excretion after intravenous administration of hydrochlorothiazide . Am J Cardiol 8:815-818, 1961.Crossref 18. The Coronary Drug Project Research Group: Serum uric acid: Its association with other risk factors and with mortality in coronary heart disease . J Chron Dis 29:557-569, 1976.Crossref 19. Gertler MM, Garn SM, Levine SA: Serum uric acid in relation to age and physique in health and in coronary heart disease . Ann Intern Med 34:1421-1431, 1951.Crossref 20. Hall AP: Correlations among hyperuricemia, hypercholesterolemia, coronary disease and hypertension . Arthritis Rheum 8:846-852, 1965.Crossref 21. Dreyfuss F: The role of hyperuricemia in coronary heart disease . Chest 38:332-334, 1960.Crossref 22. Kohn PM, Prozan GB: Hyperuricemia: Relationship to hypercholesterolemia and acute myocardial infarction . JAMA 170:1909-1912, 1959.Crossref 23. Breckenridge A: Hypertension and hyperuricaemia . Lancet 1:15-18, 1966.Crossref 24. Klinenberg JR, Bonick HC, Dornfeld L: Renal function abnormalities in patients with asymptomatic hyperuricemia . Arthritis Rheum 18( (suppl) ):725:730, 1975.Crossref 25. Wallace SL: Gout and hypertension . Arthritis Rheum 18( (suppl) ):721-723, 1975.Crossref 26. Chrysant SG, Adamopoulos P, Tsuchiya M, et al: Systemic and renal hemodynamic effects of bupicomide: A new vasodilator . Am Heart J 92:335-339, 1976.Crossref 27. Ames RP, Hill P: Elevation of serum lipid levels during diuretic therapy of hypertension . Am J Med 61:748-757, 1976.Crossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Internal Medicine American Medical Association

Ticrynafen: A Novel Uricosuric Antihypertensive Natriuretic Agent

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Publisher
American Medical Association
Copyright
Copyright © 1978 American Medical Association. All Rights Reserved.
ISSN
0003-9926
eISSN
1538-3679
DOI
10.1001/archinte.1978.03630250033013
Publisher site
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Abstract

Abstract Interest in new diuretics with less side effects has led to the synthesis of ticrynafen, an uricosuric diuretic. This agent was compared with hydrochlorothiazide in a crossover design study involving 12 hypertensive men. Both agents significantly decreased mean arterial pressure from 8% to 18% in eight of the 12 patients. In addition to reducing body weight, these diuretics induced reversible changes in BUN and carbon dioxide content (increased) and plasma concentration of potassium and chloride ions (decreased). The most important change in renal function was a 2.5-fold increase in fractional urate clearance by ticrynafen associated with reduction of serum uric acid by 62%. Thus, ticrynafen is a promising therapeutic agent in hypertension, adding a unique uricosuric effect that should improve patient compliance. (Arch Intern Med 138:53-57, 1978) References 1. Thuillier G, Laforest J, Caribou B, et al: Heterocyclin derivatives of phenoxyacetic acids, synthesis and preliminary study of their diuretic and uricosuric activities . Eur J Med Chem 9:625-633, 1974. 2. Stote RM, Cherrill DA, Erb BB, et al: Site of action of SKF 62698, a new diuretic-uricosuric agent . Clin Res 22:721A, 1974. 3. Lau K, Goldberg M, Stote R, et al: Renal effects of SKF 62698 (SKF): A new uricosuric agent . Clin Res 24:405A, 1976. 4. Stote RM, Cherril DA, Maass AR, et al: SKF 62698 (ANP3624): A diuretic with significant uricosuric activity . Sixth International Congress of Nephrology, Florence, Italy, June 5-12, 1975 , abstract 827. 5. Steele TH, Prasad DR, Reese OG: Pharmacogenesis of diuretic-induced hypouricemia , abstracted. Clin Pharmacol Ther 19:116, 1976. 6. Reese OG, Steele TH: Renal transport of urate during diuretic induced hypouricemia . Am J Med 60:973-979, 1976.Crossref 7. Masberbard A, Giudicelli C: Etude clinique de l'action antihypertensive de l'acide chloro-2,3-(thienyl-2-ceto)-phenoxyacetique en administration prolongee . Lyon Med 232:165-174, 1974. 8. Masbernard A, Giudicelli CP, Kamaludin T: Étude pharmacologique clinique de l'acide dichloro-2,3-(thienyl-c-ceto)-phenoxyacetique . J Pharmacol Clin 1976, spécial, 13-18. 9. Wood GA, Levitt SH: Simultaneous red cell mass and plasma volume determinations using 51Cr tagged red cells and 125I labeled albumin . J Nucl Med 6:433-440, 1965. 10. Smith HW, Finkelstein N, Aliminosa L, et al: The renal clearances of substituted hippuric acid derivatives and other aromatic acids in dog and man . J Clin Invest 24:388-404, 1945.Crossref 11. Tarazi RC, Dustan HP, Frohlich ED, et al: Plasma volume and chronic hypertension: Relationship to arterial pressure levels in different hypertensive diseases . Arch Intern Med 125:835-842, 1970.Crossref 12. Gifford RW Jr: Chlorothiazide in the treatment of hypertension . Postgrad Med 25:559-571, 1959. 13. Fallis NE, Ford RV: Current concepts in therapy: Limitations in the use of thiazide diuretics . N Engl J Med 263:504-505, 1960.Crossref 14. Maldonado MN, Eknoyan G, Suki WM: Diuretics in nonedematous states: Physiological basis for the clinical use . Arch Intern Med 131:797-808, 1973.Crossref 15. Paloyan E, Forland M, Pickleman JR: Hyperparathyroidism coexisting with hypertension and prolonged thiazide administration . JAMA 210:1243-1245, 1969.Crossref 16. Healey LA, Magid GJ, Decker JL: Uric acid retention due to hydrochlorothiazide . N Engl J Med 261:1358-1362, 1959.Crossref 17. Duarte C, Dreifus LS, Kodama R, et al: Pattern of uric acid excretion after intravenous administration of hydrochlorothiazide . Am J Cardiol 8:815-818, 1961.Crossref 18. The Coronary Drug Project Research Group: Serum uric acid: Its association with other risk factors and with mortality in coronary heart disease . J Chron Dis 29:557-569, 1976.Crossref 19. Gertler MM, Garn SM, Levine SA: Serum uric acid in relation to age and physique in health and in coronary heart disease . Ann Intern Med 34:1421-1431, 1951.Crossref 20. Hall AP: Correlations among hyperuricemia, hypercholesterolemia, coronary disease and hypertension . Arthritis Rheum 8:846-852, 1965.Crossref 21. Dreyfuss F: The role of hyperuricemia in coronary heart disease . Chest 38:332-334, 1960.Crossref 22. Kohn PM, Prozan GB: Hyperuricemia: Relationship to hypercholesterolemia and acute myocardial infarction . JAMA 170:1909-1912, 1959.Crossref 23. Breckenridge A: Hypertension and hyperuricaemia . Lancet 1:15-18, 1966.Crossref 24. Klinenberg JR, Bonick HC, Dornfeld L: Renal function abnormalities in patients with asymptomatic hyperuricemia . Arthritis Rheum 18( (suppl) ):725:730, 1975.Crossref 25. Wallace SL: Gout and hypertension . Arthritis Rheum 18( (suppl) ):721-723, 1975.Crossref 26. Chrysant SG, Adamopoulos P, Tsuchiya M, et al: Systemic and renal hemodynamic effects of bupicomide: A new vasodilator . Am Heart J 92:335-339, 1976.Crossref 27. Ames RP, Hill P: Elevation of serum lipid levels during diuretic therapy of hypertension . Am J Med 61:748-757, 1976.Crossref

Journal

Archives of Internal MedicineAmerican Medical Association

Published: Jan 1, 1978

References