| Class | Pulmonary vasodilator |
|---|---|
| Chemistry |
Pyrimidine derivative |
| Routes of administration |
Oral |
| Absorption |
50% oral bioavailability |
| Solubility |
pKa 5.8 |
| Distribution |
Large VOD, 28L/kg; ; highly protein-bound (98%); |
| Metabolism |
Hepatic metabolism and almost completely biliary elimination; only 3% of the dose is recovered from the urine. Only of the metabolites is effective and probably contributes 10-20% of the total drug effect |
| Elimination |
Terminal elimination half-life is about 5 hours in healthy adult subjects |
| Time course of action |
Effects are maximal ~ 1 hour following oral administration |
| Target receptor |
Endothelin receptor types ETA and ETB |
| Mechanism of action |
By competitive inhbition prevents binding of endothelin to its ETA receptor, which would usually produce smooth muscle contraction (vasoconstriction). ETA are G-protein coupled receptors; activating them leads to an increase in cAMP and an increased availability of intracellular calcium which gives rise to vasoconstriction. |
| Clinical effects |
Pulmonary vasodilation, fluid retention, pulmonary veno-occlusive disease, foetal toxicity, anaemia |
| Literature reference |
FDA information on the TRACLEER brand of bosentan |
| CICM details of understanding | Not specifically listed in the CICM syllabus |
| Mentioned around Deranged Physiology | |
| Related SAQs |