Embelin is used for the treatment of Pulmonary Arterial Hypertension (PAH) (WHO Group 1) to improve exercise capacity and delay clinical deterioration.
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Endothelin-1 (ET-1) is a powerful peptide involved in various vascular actions. It exerts its effects through two receptor subtypes: ETA and ETB. ETA primarily causes vasoconstriction and cell proliferation, while ETB induces vasodilation, antiproliferation, and ET-1 clearance. Ambrisentan is a potent ETA receptor antagonist, with over 4000 times greater selectivity for ETA over ETB. The exact clinical significance of this high selectivity is not well understood.
Ambrisentan is absorbed with peak levels appearing about 2 hours after oral administration, and food does not affect its absorption. It is highly bound to plasma proteins (99%) and eliminated through non-renal pathways. Although its terminal half-life is around 15 hours, the accumulation factor after long-term dosing indicates an effective half-life of about 9 hours.
Decreased hemoglobin levels and hematocrit have been observed in clinical trials with Embelin, similar to other endothelin receptor antagonists.
Co-administration with Cyclosporine can increase Embelin exposure by about 2-fold, so the dosage of Embelin should be limited to 5 mg once daily when taken with Cyclosporine.
Ambrisentan is contraindicated in pregnant women as it may cause fetal harm. Pregnancy must be excluded before starting treatment and prevented during treatment and for one month after stopping. It is also contraindicated in patients with Idiopathic Pulmonary Fibrosis (IPF), including those with pulmonary hypertension (WHO Group 3).
Store in a cool, dry place below 30°C, away from light and moisture.
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