Bosentan
Bosentan. Dual endothelin-A + B receptor antagonist — blocks vasoconstrictive + proliferative effects of endothelin-1 on pulmonary vasculature.… Oral half-life 5.4 h.
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.
PK: BOTH OF MY SUSPICIONS RESOLVED IN THE RECORD FAVOUR, AND SAYING SO IS THE POINT. F 0.5 VERIFIES against a real intravenous ascending-dose arm — "The absolute bioavailability was 50% and appeared to decrease with doses above 600 mg" — in a paper this record did not cite; because that volume is intravenous-derived, CLASS 6 DOES NOT APPLY. And AUTO-INDUCTION DOES NOT BREAK THE MODEL: "the exposure to bosentan was reduced by 33% WITHOUT CHANGE IN tmax AND t(1/2)", so one half-life is valid in both the first-dose and steady-state phases — the fortunate case. Its active metabolite is likewise bounded by the same paper, "less than 25% of that to bosentan both after single and multiple doses", unlike the co-equal metabolites that made two other records in this group unauthorable. t½ 5 becomes the verbatim 5.4. V 18 L was the label figure; the nearest verbatim quantity is a dose-dependent limiting value of 0.2 L/kg, intravenous-derived, carried at 70 kg. ka 0.65 reproduces nothing, implying a 3.0 h peak against an observed 4.5 h. All four references are CYP3A4 induction citations, correctly filed.
Pharmacokinetics
- Oral — t½ 5.4 h · F 50% · Vd 14 L
Related compounds
- Simvastatin — caution
- Sildenafil — caution
- Hormonal contraceptives — caution
- Ethinyl Estradiol — caution
Sources: PMID:12047483, PMID:12603176, PMID:18040672, PMID:16550733, PMID:8035319, PMID:8823230