Pharmacology: Pharmacodynamics: Mechanism of Action: Risedronate sodium is a pyridinyl bisphosphonate that binds to bone hydroxyapatite and inhibits osteoclast-mediated bone resorption. The bone turnover is reduced while the osteoblast activity and bone mineralisation is preserved.
Pharmacokinetics: Absorption: Absorption is relatively rapid [time to maximum concentration (Tmax)] of approximately 1 hr for immediate release and is independent of dose. Mean oral bioavailability is 0.63%. Dosing for the immediate-release tablet either 30 min prior to breakfast or 2 hrs after dinner reduces the extent of absorption to 55%. Absorption is reduced by food, especially by product containing calcium or other polyvalent cations. The pharmacokinetic of risedronate are dose-proportional after a single oral dose.
Distribution: In animal studies, approximately 60% of the dose is distributed to bone, with the mean steady-state volume of distribution is 13.8 L/kg. Plasma protein-binding is about 24%.
Metabolism: Risedronate is not metabolized. There is no evidence that supports system metabolism of residronate.
Excretion: Approximately 50% of the absorbed dose is excreted in urine within 24 hrs. Mean renal clearance is 105 mL/min and mean total clearance is 122 mL/min with the difference primarily reflecting nonrenal clearance or clearance caused by adsorption to bone. The renal clearance is not concentration dependent, and there is a linear relationship between renal clearance and creatinine clearance. Unabsorbed drug is eliminated unchanged in feces. The terminal expotential half-life (t½) was 561 hrs.