When this happens, pressure builds up in the tissues and muscles causing tissue ischemia. An increase in muscle weight will reduce the compartment volume of the surrounding fascial borders and result in an increased compartment pressure. An increase in the pressure of the tissue can force fluid to leak into the interstitial space (extracellular fluid), leading to a disruption of the micro-circulation of the leg. This condition occurs commonly in the lower leg and various other locations within the body, such as the foot or forearm. CECS can be seen in athletes who train rigorously in activities that involve constant repetitive actions or motions. Pathophysiology
In a normal human body, blood flow from the arterial system (higher pressure) to venous system (lower pressure) requires a pressure gradient. When this pressure gradient is diminished, blood flow from the artery to the vein is reduced. This causes a backup of blood and excessive fluid to leak from the capillary wall into spaces between the soft tissues cells, causing swelling of the extracellular space and a rise in intracompartmental pressure. This swelling of the soft tissues surrounding the blood vessels compresses the blood and lymphatic vessels further, causing more fluid to enter the extracellular spaces, leading to additional compression. The pressure continues to increase due to the non-compliant nature of the fascia containing the compartment. This worsening cycle can eventually lead to a lack of sufficient oxygen in the soft tissues (tissue ischemia) and tissue death (necrosis).
When in the circulation, about 99% of both substances are bound to plasma proteins, namely to albumin and alpha-1-acid glycoprotein to equal amounts.The liver enzymes CYP2C8 and, to a lesser extent, CYP3A4, hydroxylate and dealkylate the active substance, thereby inactivating it. Besides, ACT-333679 is glucuronidized by the enzymes UGT1A3 and UGT2B7. The terminal half-life of selexipag is 0.8 to 2.5 hours, that of the active metabolite is 6.2 to 13.5 hours. History
The U.S. Food and Drug Administration (FDA) granted selexipag orphan drug status for PAH. It was approved by the FDA on 22 December 2015.In Europe, the drug was approved in May 2016. Society and culture
Economics
The expected price for the drug in the US is $160,000 to $170,000 per patient before rebates. References
External links
"Selexipag". Drug Information Portal. U.S. National Library of Medicine. Clinical trial number NCT03187678 for "Safety Study of the Switch From Oral Selexipag to Intravenous Selexipag in Subjects With Stable Pulmonary Arterial Hypertension" at ClinicalTrials.gov