A review of pulmonary arterial hypertension | 合法藥品大搜索

由RJBarst著作·2007·被引用90次—Endothelinreceptorantagonists(ERAs)actontheendothelinpathwaybyblocking...InPhase3clinicaltrialsinpatientswithPAH,ambrisentan(2.5–10mg ...

Ambrisentan is rapidly absorbed into the systemic circulation following oral administration, with high oral bioavailability (Rubin et al 2005b[1]). The pharmacokinetics of ambrisentan are dose-linear over a range of 1–100 mg and are not affected by food intake. Steady-state is achieved after 3–4 days of once-daily oral dosing with ambrisentan, and the pharmacokinetics of multiple doses (ie, steady-state ambrisentan) are consistent with observations after a single dose (Rubin et al 2005b[2]). The steady-state elimination half-life of ambrisentan in PAH patients is approximately 15 hours for the 5 mg dose, providing the rationale for once-daily dosing (Oudiz 2006[3]; Rubin et al 2005b[4]).

The main metabolic pathways of ambrisentan appears to be hepatic phase II glucuronidation of the parent compound, and to a lesser extent phase I hydroxylation. Moreover, in vitro and in vivo animal model studies with ambrisentan concentrations that exceeded therapeutic levels...