Abstract:
BACKGROUND:The oral dual endothelin (ET) antagonist bosentan has been established as a cornerstone in the treatment of pulmonary arterial hypertension (PAH). ET is believed to be a key pathogenic mediator in systemic sclerosis (scleroderma, SSc), causing fibrotic, hypertrophic and inflammatory processes. PAH is one of the resulting deleterious effects in approximately 15% of SSc patients. MATERIALS AND METHODS:This was an open-label prospective observational study of 8 patients aged 34-73 years with symptomatic, severe PAH related to SSc (WHO class III or IV) and mostly, lung fibrosis. PAH diagnosis was ascertained with echocardiography or right heart catheterization. Patients were treated on top of diuretics and anticoagulants with bosentan 62.5 mg twice daily for 4 weeks followed by a maintenance dose of 125 mg twice daily. RESULTS:The mean 6-minute walk distance (data available in 7 patients) increased from 71.9 (+/- 54.7) m at baseline to 191.9 (+/- 104.6) m after 3 months (P = 0.012) and to 202.6 (+/- 108.1) m after 6 months (P = 0.011), respectively. Six of 8 patients improved in the 6-minute walk test, and these 6 patients also improved in World Health Organization functional class. Two patients did not sufficiently respond to bosentan therapy; one of them died. The tolerability of bosentan was good, and there were no discontinuations. Elevations of hepatic aminotransferases above 3 times the upper limit of normal were not recorded. CONCLUSION:Bosentan treatment was well tolerated in this cohort of SSc patients with interstitial lung disease and was effective for treatment of severe PAH in the majority of patients.
journal_name
Eur J Clin Investjournal_title
European journal of clinical investigationauthors
Ahmadi-Simab K,Hellmich B,Gross WLdoi
10.1111/j.1365-2362.2006.01695.xsubject
Has Abstractpub_date
2006-09-01 00:00:00pages
44-8eissn
0014-2972issn
1365-2362pii
ECI1695journal_volume
36 Suppl 3pub_type
杂志文章abstract::The ATP-binding cassette transporter P-glycoprotein is now recognized as an important determinant for disposition of multiple drugs. The use of P-glycoprotein-expressing cell lines, the generation of P-glycoprotein knockout mice as well as studies in animals and humans contributed to a better understanding on the role...
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journal_title:European journal of clinical investigation
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journal_title:European journal of clinical investigation
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journal_title:European journal of clinical investigation
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journal_title:European journal of clinical investigation
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journal_title:European journal of clinical investigation
pub_type: 临床试验,杂志文章
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journal_title:European journal of clinical investigation
pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:1992-10-01 00:00:00
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journal_title:European journal of clinical investigation
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journal_title:European journal of clinical investigation
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更新日期:1992-10-01 00:00:00
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journal_title:European journal of clinical investigation
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更新日期:1998-05-01 00:00:00