Osteorise Mechanism of Action

Pharmacology: Mechanism of Action: At the cellular level, Risedronate Sodium (Osteorise) inhibits osteoclasts. The osteoclasts adhere normally to the bone surface, but show evidence of reduced active resorption.
Pharmacokinetics: Absorption: Absorption after an oral dose is relatively rapid (tmax~1 hour) and occurs throughout the upper gastrointestinal tract. The fraction of the dose absorbed is independent of dose over the range studied (single dose, 2.5 to 30 mg; multiple dose, 2.5 to 5 mg). Dosing 1 hour prior to breakfast reduces the extent of absorption by 30% compared to dosing in the fasting state. Dosing either 0.5 hours prior to breakfast or 2 hours after dinner (evening meal) results in a similar extent of absorption. Risedronate Sodium (Osteorise) is effective when administered at least 30 minutes before breakfast.
Distribution: The mean steady-state volume of distribution is 6.3 L/kg in humans. Plasma protein binding of drug is about 24%.
Metabolism: There is no evidence of systemic metabolism of risedronate sodium.
Excretion: Approximately half of the absorbed dose is excreted in urine within 24 hours. Unabsorbed drug is eliminated unchanged in feces. Once risedronate is absorbed, the serum concentration-time profile is multi-phasic, with an initial half-life of about 1.5 hours and a terminal exponential half-life of 480 hours. This terminal half-life is hypothesized to represent the dissociation of risedronate from the surface of bone.
Special populations: Renal insufficiency: Risedronate is excreted unchanged primarily via the kidney. Risedronate Sodium (Osteorise) is not recommended for use in patients with severe renal impairment (creatinine clearance < 30 mL/min) because of lack of clinical experience. No dosage adjustment is necessary in patients with a creatinine clearance ≥30 mL/min.
Hepatic insufficiency: No studies have been performed to assess risedronate's safety or efficacy in patients with hepatic impairment. But dosage adjustment is unlikely to be needed in patients with hepatic impairment.