| Class | Pulmonary vasodilator |
|---|---|
| Chemistry |
Propionic acid |
| Routes of administration |
Oral |
| Absorption |
90% oral bioavailability |
| Solubility |
This drug is a carboxylic acid with a pKa of 4 |
| Distribution |
Large VOD, 40L/kg; 99% protein bound |
| Metabolism |
Ambrisentan is excreted largely unchanged (45.6% of the dose); excretion is biliary. The rest is glucouronidated and oxidised by CYP3A4 into relatively inactive metabolites |
| Elimination |
In humans, the terminal half-life following oral administration was determined to be approximately 15 hours |
| Time course of action |
Maximum plasma concentrations (Cmax) of ambrisentan typically occur around 1.5 hours post dose |
| 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, LFT derangedment ("transaminitis"), |
| Literature reference |
TGA information pamphlet for the VOLIBRIS brand of ambrisentan |
| CICM details of understanding | Not specifically listed in the CICM syllabus |
| Mentioned around Deranged Physiology | |
| Related SAQs |