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The monitoring of warfarin and keeping the international normalized ratio (INR) between 2.0 and 3.0, along with avoiding over and under treatment, has driven a search for an alternative. [ 3 ] [ 14 ] A naturally occurring inhibitor of factor Xa was reported in 1971 by Spellman et al. from the dog hookworm. [ 15 ]
Apixaban, sold under the brand name Eliquis, is an anticoagulant medication used to treat and prevent blood clots and to prevent stroke in people with nonvalvular atrial fibrillation through directly inhibiting factor Xa.
Rivaroxaban (Xarelto) was the first approved FXa inhibitor to become commercially available in Europe and Canada in 2008. [1] The second one was apixaban (Eliquis), approved in Europe in 2011 [2] and in the United States in 2012. [3] The third one edoxaban (Lixiana, Savaysa) was approved in Japan in 2011 and in Europe and the US in 2015. [4]
The juxtaglomerular apparatus is part of the kidney nephron, next to the glomerulus. It is found between afferent arteriole and the thick ascending limb of the loop of Henle (distal straight tubule) of the same nephron. This location is critical to its function in regulating renal blood flow and glomerular filtration rate. [2] [3]
It uses Na-H antiport, Na-glucose symport, sodium ion channels (minor). [1] It is stimulated by angiotensin II and aldosterone, and inhibited by atrial natriuretic peptide. It is very efficient, since more than 25,000 mmol/day of sodium is filtered into the nephron, but only ~100 mmol/day, or less than 0.4% remains in the final urine.
Andexanet alfa, sold under the brand name Andexxa among others, is an antidote for the medications rivaroxaban and apixaban, when reversal of anticoagulation is needed due to uncontrolled bleeding. [8]
Each substance has a specific clearance that depends on how the substance is handled by the nephron. Clearance is a function of 1) glomerular filtration, 2) secretion from the peritubular capillaries to the nephron, and 3) reabsorption from the nephron back to the peritubular capillaries.
Fig.1) Schematic diagram of the nephron (yellow), relevant circulation (red/blue), and the four methods of altering the filtrate. The nephron is the functional unit of the kidney. [3] This means that each separate nephron is where the main work of the kidney is performed. A nephron is made of two parts: