European journal of clinical investigation
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Eur. J. Clin. Invest. · Sep 2006
Bosentan for the treatment of pulmonary arterial hypertension associated with congenital heart defects.
Bosentan is an effective first-line therapy in New York Heart Association (NYHA) III patients with idiopathic pulmonary arterial hypertension (PAH). Pre-clinical data support the rationale for the potential benefit of bosentan in PAH associated with congenital heart disease (CHD). ⋯ Bosentan improves exercise capacity, functional class and haemodynamics in most patients with PAH-associated CHD, without serious side-effects, suggesting bosentan may be an important treatment option for these patients.
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Eur. J. Clin. Invest. · Sep 2006
Bosentan therapy of pulmonary arterial hypertension in connective tissue diseases.
Pulmonary arterial hypertension (PAH) is a life-threatening and debilitating complication of several connective tissue diseases. We aimed to evaluate the effects of long-term treatment with bosentan, an oral dual endothelin ET(A)/ET(B) receptor antagonist, in a cohort of patients with PAH related to connective tissue diseases. ⋯ Long-term treatment with bosentan was effective in improving exercise capacity and pulmonary haemodynamics in patients with PAH related to connective tissue diseases.
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Eur. J. Clin. Invest. · Sep 2006
In vivo and mechanistic evidence of nuclear receptor CAR induction by artemisinin.
Artemisinin (a sesquiterpene lactone endoperoxide) has become important in multi-drug treatment of malaria. There is evidence that artemisinin induces drug metabolism which could result in drug-drug interactions. The objective of this study was to characterize the inductive properties of artemisinin on drug-metabolizing cytochrome P450 (CYP450) enzymes. ⋯ The results demonstrate that the drug exerts its effects on drug metabolism via the CAR receptor that results in up-regulation of genes such as the Cyp2b. The weaker up-regulation of CYP2A5 might also be CAR-dependent or alternatively, a consequence of artemisinin toxicity. The results of this study are of importance when predicting potential drug-drug interactions in multi-drug therapies with artemisinin.
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Eur. J. Clin. Invest. · Sep 2006
Randomized Controlled TrialSurvival in patients with pulmonary arterial hypertension treated with first-line bosentan.
Pulmonary arterial hypertension (PAH) is a devastating disease of the small pulmonary arteries and arterioles, characterized by intimal fibrosis, medial hypertrophy and plexiform lesions. When untreated both the idiopathic form (IPAH, formerly termed primary pulmonary hypertension, PPH) and PAH related to various other conditions such as scleroderma (SSc) often take a progressive course with high mortality. There is ongoing search for disease-specific treatments that are able to improve survival in these patients. The oral dual endothelin (ET(A)/ET(B)) antagonist bosentan has been shown to improve exercise capacity, time to clinical worsening, haemodynamics and quality of life in short-term studies. ⋯ The present analyses suggest that first-line bosentan therapy, followed by the addition of other disease-specific therapies as required, improves survival in patients with advanced PAH.