Pharmacokinetics and pharmacodynamics of the endothelin‐receptor antagonist bosentan in healthy human subjects

  title={Pharmacokinetics and pharmacodynamics of the endothelin‐receptor antagonist bosentan in healthy human subjects},
  author={Cornelia Weber and Rita Schmitt and Herbert Birnboeck and G{\'e}rard Hopfgartner and Sjoerd P. Marle and Pierre A. M. Peeters and Jan H. G. Jonkman and Charles‐Richard Jones},
  journal={Clinical Pharmacology \& Therapeutics},
In vivo and in vitro studies exploring the pharmacokinetic interaction between bosentan, a dual endothelin receptor antagonist, and glyburide
In a clinical trial with patients with chronic heart failure, a higher incidence ofelevated levels of liver transaminases was observed during concomitant treatment with bosentan, a dual endothelin
A receptor selective antagonist BMS-193884 in healthy men
This work investigated the haemodynamic effects of locally and systemically active doses of BMS-193884, an endothelin A (ET A ) receptor selective ERA, and its influence on vasoconstriction to Endothelin-1 (ET-1) in healthy men.
La pharmacologie de l'endothéline et de son antagoniste bosentan
Preclinical and clinical data suggest that bosentan might become a new approach for the chronic treatment of these cadiovascular and pulmonary diseases.
Endothelin Ligands and their Experimental Effects Within the Human Circulation
A number of endothelin (ET) receptor antagonists have been developed as research tools and as potential medicines and several are at various stages of clinical evaluation.
Pharmacokinetics and pharmacodynamic effects of ABT-627, an oral ETA selective endothelin antagonist, in humans.
The data suggest that ABT-627 may be a valuable tool in treatment of cardiovascular disease because it is well tolerated, rapidly absorbed, effectively blocks ET-1 induced vasoconstriction and causes a decrease in total peripheral resistance and mean arterial pressure.
Dual ETA/ETB vs. selective ETA endothelin receptor antagonism in patients with pulmonary hypertension
To answer the question of whether selective or dual ETRA is preferable in patients with PAH, experimental and clinical data with relevance to the pulmonary circulation are reviewed in this article.
Protection against aspirin‐induced human gastric mucosal injury by bosentan, a new endothelin‐1 receptor antagonist
  • DugganStack Hawkey
  • Medicine, Biology
    Alimentary pharmacology & therapeutics
  • 1999
Gastric ulceration induced by aspirin and by non‐steroidal anti‐inflammatory drugs (NSAIDs) is a major clinical problem and there is evidence that NSAID‐induced injury may cause endothelin activation.
Bosentan and the endothelin system in congestive heart failure
Early clinical experience with bosentan has confirmed some benefits on hemodynamic parameters in patients with CHF, and its role in slowing the progression of the disease and improving survival remains to be elucidated.


The effect of bosentan, a new potent endothelin receptor antagonist, on the pathogenesis of cerebral vasospasm.
In the dogs treated with bosentan, theBA spasm on Day 7 was significantly ameliorated compared with the BA spasm in the untreated dogs, which might indicate whether or not ET is involved in the pathogenesis of cerebral vasospasm.
Pharmacologic target‐mediated drug disposition
  • G. Levy
  • Biology, Psychology
    Clinical pharmacology and therapeutics
  • 1994
Clinical Pharmacology and Therapeutics (1994) 56, 248–252; doi:10.1038/clpt.1994.134
Pharmacological characterization of bosentan, a new potent orally active nonpeptide endothelin receptor antagonist.
Bosentan is the most potent orally active antagonist of ET receptors described so far and its pharmacological profile makes bosentan a potentially useful drug in the management of clinical disorders associated with vasoconstriction.
Endothelin receptor antagonists inhibit endothelin in human skin microcirculation.
Endothelin is a potent vasoconstrictor peptide produced by endothelial cells, but its role in physiology and disease is uncertain and a double injection model was developed, allowing simultaneous injection of two substances.
Clearance of circulating endothelin-1 by ETB receptors in rats.
It is suggested that ETB receptors play an important role in the clearance of ET-1, as about 80% of bolus-injected [125I]ET-1 was retained by the lungs after one passage.
Role of endothelin in the maintenance of blood pressure in conscious rats with chronic heart failure. Acute effects of the endothelin receptor antagonist Ro 47-0203 (bosentan).
Endothelin plays a role in the maintenance of blood pressure in CHF rats, as evidenced by the significant reduction in mean arterial pressure after oral administration of bosentan, and endothelin antagonists may be useful therapeutic agents in the treatment of CHF.
Radioimmunological Determination of Endothelin Peptides in Human Plasma: A Methodological Approach
For the first time, the concentrations of immunoreactive ET-1 determined in plasma after silica gel extraction were confirmed by a radio receptor assay and by specific immunoextraction.