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Hemodynamic effects of bosentan, an endothelin receptor antagonist, in patients with pulmonary hypertension
Few treatments are available for isolated pulmonary hypertension (PHT), which has a high morbidity and mortality. This trial was designed to assess the hemodynamic effects of bosentan, an endothelin receptor antagonist, in patients with PHT, in which local overproduction of endothelin-1 (ET-1) is th...
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| Published in: | Circulation (New York, N.Y.) N.Y.), 2000-07, Vol.102 (4), p.411-418 |
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| container_end_page | 418 |
| container_issue | 4 |
| container_start_page | 411 |
| container_title | Circulation (New York, N.Y.) |
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| creator | WILLIAMSON, D. J WALLMAN, L. L JONES, R KEOGH, A. M SCROOPE, F PENNY, R WEBER, C MACDONALD, P. S |
| description | Few treatments are available for isolated pulmonary hypertension (PHT), which has a high morbidity and mortality. This trial was designed to assess the hemodynamic effects of bosentan, an endothelin receptor antagonist, in patients with PHT, in which local overproduction of endothelin-1 (ET-1) is thought to play a pathogenic role.
An open-label, dose-ranging study was performed in 7 female patients with primary PHT (n=5) or isolated PHT associated with limited scleroderma (n=2). Infusions of 50, 150, and 300 mg were administered at 2-hour intervals, and the hemodynamic responses were measured. Bosentan caused a dose-dependent fall in total pulmonary resistance (-20.0+/-11.0%, P=0.01) and mean pulmonary artery pressure (-10.6+/-11.0%, P>0.05). However, there was also a fall in the systemic vascular resistance (-26.2+/-12.8%, P |
| doi_str_mv | 10.1161/01.CIR.102.4.411 |
| format | article |
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An open-label, dose-ranging study was performed in 7 female patients with primary PHT (n=5) or isolated PHT associated with limited scleroderma (n=2). Infusions of 50, 150, and 300 mg were administered at 2-hour intervals, and the hemodynamic responses were measured. Bosentan caused a dose-dependent fall in total pulmonary resistance (-20.0+/-11.0%, P=0.01) and mean pulmonary artery pressure (-10.6+/-11.0%, P>0.05). However, there was also a fall in the systemic vascular resistance (-26.2+/-12.8%, P<0.005) and mean arterial pressure (-19.8+/-14.4%, P<0.001). There was a slight increase in cardiac index (15+/-12%, P>0.05) and a dose-dependent rise in ET-1 but no significant change in other hemodynamic variables, gas exchange, or other vasoactive mediators.
Intravenous bosentan is a potent but nonselective pulmonary vasodilator at the doses tested, even in patients resistant to inhaled nitric oxide. Transient increases in plasma ET-1 were observed, consistent with a blockade of endothelial ET(B) receptors. Systemic hypotension and other significant events during the study indicate that its intravenous use in patients with severe PHT may be limited. Implications for future trial design and studies of chronic oral treatment are discussed.</description><identifier>ISSN: 0009-7322</identifier><identifier>EISSN: 1524-4539</identifier><identifier>DOI: 10.1161/01.CIR.102.4.411</identifier><identifier>PMID: 10908213</identifier><identifier>CODEN: CIRCAZ</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins</publisher><subject>Adult ; Aged ; Antihypertensive agents ; Antihypertensive Agents - administration & dosage ; Antihypertensive Agents - adverse effects ; Biological and medical sciences ; Bosentan ; Cardiovascular system ; Endothelin Receptor Antagonists ; Female ; Hemodynamics - drug effects ; Humans ; Hypertension, Pulmonary - drug therapy ; Hypertension, Pulmonary - physiopathology ; Infusions, Intravenous ; Medical sciences ; Middle Aged ; Pharmacology. Drug treatments ; Sulfonamides - administration & dosage ; Sulfonamides - adverse effects</subject><ispartof>Circulation (New York, N.Y.), 2000-07, Vol.102 (4), p.411-418</ispartof><rights>2000 INIST-CNRS</rights><rights>Copyright American Heart Association, Inc. Jul 25, 2000</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c481t-625512020bb2380dac5887092eedc2da8e01ba8d1ca363ec5af0ab452cb83c013</citedby><cites>FETCH-LOGICAL-c481t-625512020bb2380dac5887092eedc2da8e01ba8d1ca363ec5af0ab452cb83c013</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1453102$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10908213$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>WILLIAMSON, D. J</creatorcontrib><creatorcontrib>WALLMAN, L. L</creatorcontrib><creatorcontrib>JONES, R</creatorcontrib><creatorcontrib>KEOGH, A. M</creatorcontrib><creatorcontrib>SCROOPE, F</creatorcontrib><creatorcontrib>PENNY, R</creatorcontrib><creatorcontrib>WEBER, C</creatorcontrib><creatorcontrib>MACDONALD, P. S</creatorcontrib><title>Hemodynamic effects of bosentan, an endothelin receptor antagonist, in patients with pulmonary hypertension</title><title>Circulation (New York, N.Y.)</title><addtitle>Circulation</addtitle><description>Few treatments are available for isolated pulmonary hypertension (PHT), which has a high morbidity and mortality. This trial was designed to assess the hemodynamic effects of bosentan, an endothelin receptor antagonist, in patients with PHT, in which local overproduction of endothelin-1 (ET-1) is thought to play a pathogenic role.
An open-label, dose-ranging study was performed in 7 female patients with primary PHT (n=5) or isolated PHT associated with limited scleroderma (n=2). Infusions of 50, 150, and 300 mg were administered at 2-hour intervals, and the hemodynamic responses were measured. Bosentan caused a dose-dependent fall in total pulmonary resistance (-20.0+/-11.0%, P=0.01) and mean pulmonary artery pressure (-10.6+/-11.0%, P>0.05). However, there was also a fall in the systemic vascular resistance (-26.2+/-12.8%, P<0.005) and mean arterial pressure (-19.8+/-14.4%, P<0.001). There was a slight increase in cardiac index (15+/-12%, P>0.05) and a dose-dependent rise in ET-1 but no significant change in other hemodynamic variables, gas exchange, or other vasoactive mediators.
Intravenous bosentan is a potent but nonselective pulmonary vasodilator at the doses tested, even in patients resistant to inhaled nitric oxide. Transient increases in plasma ET-1 were observed, consistent with a blockade of endothelial ET(B) receptors. Systemic hypotension and other significant events during the study indicate that its intravenous use in patients with severe PHT may be limited. Implications for future trial design and studies of chronic oral treatment are discussed.</description><subject>Adult</subject><subject>Aged</subject><subject>Antihypertensive agents</subject><subject>Antihypertensive Agents - administration & dosage</subject><subject>Antihypertensive Agents - adverse effects</subject><subject>Biological and medical sciences</subject><subject>Bosentan</subject><subject>Cardiovascular system</subject><subject>Endothelin Receptor Antagonists</subject><subject>Female</subject><subject>Hemodynamics - drug effects</subject><subject>Humans</subject><subject>Hypertension, Pulmonary - drug therapy</subject><subject>Hypertension, Pulmonary - physiopathology</subject><subject>Infusions, Intravenous</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Pharmacology. 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Drug treatments</topic><topic>Sulfonamides - administration & dosage</topic><topic>Sulfonamides - adverse effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>WILLIAMSON, D. J</creatorcontrib><creatorcontrib>WALLMAN, L. L</creatorcontrib><creatorcontrib>JONES, R</creatorcontrib><creatorcontrib>KEOGH, A. M</creatorcontrib><creatorcontrib>SCROOPE, F</creatorcontrib><creatorcontrib>PENNY, R</creatorcontrib><creatorcontrib>WEBER, C</creatorcontrib><creatorcontrib>MACDONALD, P. 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S</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Hemodynamic effects of bosentan, an endothelin receptor antagonist, in patients with pulmonary hypertension</atitle><jtitle>Circulation (New York, N.Y.)</jtitle><addtitle>Circulation</addtitle><date>2000-07-25</date><risdate>2000</risdate><volume>102</volume><issue>4</issue><spage>411</spage><epage>418</epage><pages>411-418</pages><issn>0009-7322</issn><eissn>1524-4539</eissn><coden>CIRCAZ</coden><abstract>Few treatments are available for isolated pulmonary hypertension (PHT), which has a high morbidity and mortality. This trial was designed to assess the hemodynamic effects of bosentan, an endothelin receptor antagonist, in patients with PHT, in which local overproduction of endothelin-1 (ET-1) is thought to play a pathogenic role.
An open-label, dose-ranging study was performed in 7 female patients with primary PHT (n=5) or isolated PHT associated with limited scleroderma (n=2). Infusions of 50, 150, and 300 mg were administered at 2-hour intervals, and the hemodynamic responses were measured. Bosentan caused a dose-dependent fall in total pulmonary resistance (-20.0+/-11.0%, P=0.01) and mean pulmonary artery pressure (-10.6+/-11.0%, P>0.05). However, there was also a fall in the systemic vascular resistance (-26.2+/-12.8%, P<0.005) and mean arterial pressure (-19.8+/-14.4%, P<0.001). There was a slight increase in cardiac index (15+/-12%, P>0.05) and a dose-dependent rise in ET-1 but no significant change in other hemodynamic variables, gas exchange, or other vasoactive mediators.
Intravenous bosentan is a potent but nonselective pulmonary vasodilator at the doses tested, even in patients resistant to inhaled nitric oxide. Transient increases in plasma ET-1 were observed, consistent with a blockade of endothelial ET(B) receptors. Systemic hypotension and other significant events during the study indicate that its intravenous use in patients with severe PHT may be limited. Implications for future trial design and studies of chronic oral treatment are discussed.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins</pub><pmid>10908213</pmid><doi>10.1161/01.CIR.102.4.411</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Circulation (New York, N.Y.), 2000-07, Vol.102 (4), p.411-418 |
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| subjects | Adult Aged Antihypertensive agents Antihypertensive Agents - administration & dosage Antihypertensive Agents - adverse effects Biological and medical sciences Bosentan Cardiovascular system Endothelin Receptor Antagonists Female Hemodynamics - drug effects Humans Hypertension, Pulmonary - drug therapy Hypertension, Pulmonary - physiopathology Infusions, Intravenous Medical sciences Middle Aged Pharmacology. Drug treatments Sulfonamides - administration & dosage Sulfonamides - adverse effects |
| title | Hemodynamic effects of bosentan, an endothelin receptor antagonist, in patients with pulmonary hypertension |
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