Rivarox-20 Mechanism of Action

Pharmacotherapeutic group: Direct factor Xa inhibitors. ATC code: B01AF01.
Pharmacology: Pharmacodynamics: Rivaroxaban is a highly selective direct factor Xa inhibitor with oral bioavailability.
Pharmacokinetics: Absorption: Rivaroxaban is rapidly absorbed with maximum concentrations (C_max) appearing 2-4 hours after tablet intake.
Oral absorption of rivaroxaban is almost complete and oral bioavailability is high (80-100%) for the 10 mg tablet dose, irrespective of fasting/fed conditions. Intake with food does not affect rivaroxaban AUC or C_max at the 10 mg dose. Rivaroxaban 10 mg tablets can be taken with or without food.
Due to reduced extent of absorption an oral bioavailability of 66% was determined for the 20 mg tablet under fasting conditions. When rivaroxaban 20 mg tablets are taken together with food increases in mean AUC by 39% were observed when compared to tablet under fasting conditions, indicating almost complete absorption and high oral bioavailability. Rivaroxaban 20 mg should be taken with food. Under fed condition rivaroxaban 10 mg, 15 mg and 20 mg tablets demonstrated dose-proportionality.
Variability in rivaroxaban pharmacokinetics is moderate with inter-individual variability (CV%) ranging from 30% to 40%.
Distribution: Plasma protein binding in humans is high at approximately 92% to 95%, with serum albumin being the main binding component. The volume of distribution is moderate with V_ss being approximately 50 L.
Metabolism and Elimination: Of the administered rivaroxaban dose, approximately ²/₃ undergoes metabolic degradation, with half then being eliminated renally and the other half eliminated by the faecal route. The final ¹/₃ of the administered dose undergoes direct renal excretion as unchanged active substance in the urine, mainly via active renal secretion.
Rivaroxaban is metabolised via CYP3A4, CYP2J2 and CYP-independent mechanisms. Oxidative degradation of the morpholinone moiety and hydrolysis of the amide bonds are the major sites of biotransformation. Based on in vitro investigations rivaroxaban is a substrate of the transporter proteins P-gp (P-glycoprotein) and Bcrp (breast cancer resistance protein).
Unchanged rivaroxaban is the most important compound in human plasma, with no major or active circulating metabolites being present. With a systemic clearance of about 10 L/h, rivaroxaban can be classified as a low-clearance substance. Elimination of rivaroxaban from plasma occurs with terminal half-lives of 5 to 9 hours in young individuals, and with terminal half-lives of 11 to 13 hours in the elderly.