Pharmacodynamic and pharmacokinetic properties of ET receptor antagonists approved for clinical use
| Bosentan | Macitentan | Active Metabolite of Macitentan | Ambrisentan | Sitaxentan (Withdrawn from Clinical Use in 2010) | |
|---|---|---|---|---|---|
| Trade name | Tracleer, | Opsumit | Letairis, Volibris | Thelin | |
| Chemical Name | benzenesulfonamide | sulfamide | sulfamide | benzenepropanoic acid | 3-thiophenesulfonamide |
| Inhibition [125I]-ET-1 IC50 (nM, *Ki) | |||||
| ETA | 5* | 0.5 | 3 | 0.3 | 1 |
| ETB | 97* | 391 | 185 | 185 | 9800 |
| ET plasma levels after administration | ↑↑ | ↑↑ | — | ↑ | ↓ |
| Bioavailability | ∼50% | Not reported | Not reported | High | 70–100% |
| Time to max plasma concentration | 3–5 | 4-12 | 30 | 1.7–3.3 | 1–4 |
| Terminal half-life (h) | 5.4 | 16 | 40.2-65.6 | 15 | 10 |
| Excretion in urine (%) | <3 | 50% | — | Low | 50–60 |
(Weber et al., 1996;1999; Spence et al., 2008; Opitz et al., 2008; Sidharta et al., 2013)