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Apixaban is a highly selective, orally bioavailable, and reversible direct inhibitor of free and clot-bound factor Xa. Factor Xa catalyzes the conversion of prothrombin to thrombin, the final enzyme in the coagulation cascade that is responsible for fibrin clot formation. [ 27 ]
In dog testing, this compound with a carboxamide group called 13F, showed a great pharmacokinetical profile, a low clearance and adequate half-life and volume of distribution. Due to the success of finding a stabilizing group, SAR research for S1 binding moiety (p-methoxyphenyl) was discontinued.
In these cases, clearance is almost synonymous with renal clearance or renal plasma clearance. 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 ...
Clearance is therefore expressed as the plasma volume totally free of the drug per unit of time, and it is measured in units of volume per units of time. Clearance can be determined on an overall, organism level («systemic clearance») or at an organ level (hepatic clearance, renal clearance etc.). The equation that describes this concept is:
[14] [15] Renal clearance and degradation account for the most part for the systemic clearance of desulfatohirudins and there is accumulation of the drug in patients with chronic kidney disease. These drugs should not be used in patients with impaired renal function, since there is no specific antidote available to reverse the effects. [14]
The "Hepatic Extraction Ratio" is a similar measurement for clearance of a substance (usually a pharmacological drug) by the liver. It is defined as the fraction of drug removed from blood by the liver, and depends on 3 factors— the hepatic blood flow, the uptake into the hepatocytes, and the enzyme metabolic capacity.
This is a table of permselectivity for different substances in the glomerulus of the kidney in renal filtration. Substance Approximate molecular mass (g/mol) [1]
In pharmacology, augmented renal clearance (ARC) is a phenomenon where certain critically ill patients may display increased clearance of a medication through the kidneys. In many cases, it is observed as a measured creatinine clearance above that which is expected given the patient's age, gender, and other factors.