Ambrisentan

The main ingredient of this product is ambrisentan.

The main ingredient of this product is ambrisentan, chemical name: ()-(2S)-2-[(4,6-dimethylpyrimidin-2-yl)oxy]-3-methoxy-3,3-diphenylpropionic acid Chemical structure: Molecular formula: C22H22N2O4 Molecular weight: 378.42

In vitro studies using human liver tissue have shown that ambrisentan is metabolized by CYP3A, CYP2C19, 5'-diphosphoglucosyltransferases (UGTs), 1A9S, 2B7S, and 1A3S. In vitro studies suggest that ambrisentan is a substrate for organic anion transporters (OATPs) and a substrate (but not an inhibitor) of P-gp. In vivo studies Co-administration of ambrisentan with the following drugs did not result in clinically significant changes in ambrisentan exposure: Ketoconazole Omeprazole Sildenafil or Tadalafil = Rifampicin Co-administration of ambrisentan did not result in changes in exposure of the following drugs: Warfarin Digoxin Sildenafil or Tadalafil Ethinyl estradiol/norethindrone Cyclosporine A A clinical trial in healthy subjects showed that a steady-state dose of 10 mg ambrisentan did not significantly affect the single-dose pharmacokinetics of the ethinyl estradiol or norethindrone components of the combined oral contraceptive (Ortho-Novum 1/35). Based on this pharmacokinetic study, ambrisentan is not expected to affect the exposure of estrogen or progestin contraceptives. Co-administration of ambrisentan with cyclosporine A (an inhibitor of P-gp and OATP) increased steady-state plasma concentrations of ambrisentan by 2-fold in healthy volunteers. Therefore, if used in combination with cyclosporine A, the dose of ambrisentan should be controlled within 5 mg once a day (see [Dosage and Administration] section). No clinically significant effect of ambrisentan on the exposure of cyclosporine A was observed (see [Pharmacokinetics] section). After the first co-administration of ambrisentan and rifampicin (an inhibitor of OATP, a strong inducer of CYP3A and 2C19, and an inducer of P-gp and UGTs) in healthy volunteers, the exposure of ambrisentan increased transiently (approximately 2 times). However, on the 7th day after administration, the stable administration of rifampicin had no clinically relevant effect on the exposure of ambrisentan. Therefore, when used in combination with rifampicin, there is no need to adjust the dose of ambrisentan (see [Pharmacokinetics] section).

Chemical name: ()-(2S)-2-[(4,6-dimethylpyrimidin-2-yl)oxy]-3-methoxy-3,3-diphenylpropionic acid Chemical structure: Molecular formula: C22H22N2O4 Molecular weight: 378.42

In vitro studies using human liver tissue have shown that ambrisentan is metabolized by CYP3A, CYP2C19, 5-bisphosphoglucosyltransferases (UGTs), 1A9S, 2B7S, and 1A3S. In vitro studies suggest that ambrisentan is a substrate for organ anion transporters (OATPs) and a substrate (but not an inhibitor) of P-gp. In vivo studies Co-administration of ambrisentan with the following drugs did not result in clinically significant changes in ambrisentan exposure: · Ketoconazole · Omeprazole · Sildenafil · Tadalafil Co-administration of ambrisentan did not result in changes in exposure to the following drugs: · Warfarin · Digoxin · Sildenafil · Tadalafil · Ethinyl estradiol/norethindrone A clinical trial in healthy subjects showed that a steady-state dose of 10 mg ambrisentan did not significantly affect the single-dose pharmacokinetics of the ethinyl estradiol or norethindrone components of the combined oral contraceptive (Ortho-Novum 1/35). Based on this pharmacokinetic study, ambrisentan is not expected to affect the exposure of estrogen or progestin contraceptives. After co-administration with cyclosporine A (an inhibitor of P-gp and OATP), the steady-state blood concentration of ambrisentan in healthy volunteers increased by 2 times. Therefore, if co-administered with cyclosporine A, the dose of ambrisentan should be controlled within 5 mg once a day (see the [Dosage and Administration] section). No clinically significant effect of ambrisentan on the exposure of cyclosporine A was observed (see the [Pharmacokinetics] section). The first co-administration of ambrisentan and rifampicin (an inhibitor of OATP, a strong inducer of CYP3A and 2C19, a P-gp and...