Dual endothelin-A + B receptor antagonist — blocks vasoconstrictive + proliferative effects of endothelin-1 on pulmonary vasculature. Approved for pulmonary arterial hypertension. Hepatotoxicity (REMS program) + teratogenicity. Strong CYP3A4 inducer.
Half-Life (t½)
PO: 5h
Dosing Guidelines
PO: Typical 125 mg (Range: 62.5–125 mg)
Target Organ Systems
cardiovascular
respiratory
digestive
Interactions
Simvastatin (caution): CYP3A4 induction. Dingemanse 2003 (PMID:12603176) verbatim: "bosentan significantly reduced exposure to simvastatin and beta-hydroxyacid simvastatin by 34 and 46%, respectively". 9 healthy males, 3-period crossover, bosentan 125 mg bid × 5.5d + simvastatin 40 mg qd × 6d. Parent AUC ratio 0.66 → induction_factor 1/0.66 = 1.52. Per the paper: "in vivo bosentan is also a mild inducer of CYP3A4".
Sildenafil (caution): CYP3A4 induction. Burgess 2008 (PMID:18040672) verbatim: "bosentan decreased ... the area under the plasma concentration versus time curve over a dosing interval (AUC(tau)) by 62.6% (90% CI 56.8-67.7%)". 55 healthy male volunteers, randomized double-blind placebo-controlled parallel, sildenafil 20→80 mg tid + bosentan 125 mg bid × 11d. AUC ratio 0.374 → induction_factor 2.67. Note: PAH patients often need both for combo therapy; sildenafil dose adjustment.
Hormonal contraceptives (caution): CYP3A4 induction. van Giersbergen 2006 (PMID:16550733) verbatim: bosentan "significantly decreased the AUC of norethisterone and ethinyl estradiol by 13.7% (-23.5, -2.6) and 31.0% (-40.5,-20.2), respectively". 20 healthy women, randomized 2-way crossover, bosentan 125 mg bid × 7d + Ortho-Novum (1 mg NE + 35 µg EE). EE basis: AUC ratio 0.69 → induction_factor 1.45. "In an individual subject ... maximum decrease ... was 56% and 66%" — contraceptive failure risk.