Distribution

Approximately 50% of calcium in the serum is in the physiologically active ionized form; about 10% is complexed to phosphate, citrate or other anions. The remaining 40% is bound to proteins, primarily albumin.

Unabsorbed calcium from the small intestine is excreted in the feces. Renal excretion depends largely on glomerular filtration and calcium tubular reabsorption with more than 98% of calcium reabsorbed from the glomerular filtrate. This process is regulated by active vitamin D and PTH.

Risedronate pharmacokinetics have not been studied in patients <18 years of age.

Bioavailability and pharmacokinetics following oral administration are similar in men and women.

Bioavailability and disposition are similar in elderly (>60 years of age) and younger subjects. No dosage adjustment is necessary.

Pharmacokinetic differences due to race have not been studied.

Risedronate is excreted unchanged primarily via the kidney. As compared to persons with normal renal function, the renal clearance of risedronate was decreased by about 70% in patients with creatinine clearance of approximately 30 mL/min. ACTONEL 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.

No studies have been performed to assess risedronates safety or efficacy in patients with hepatic impairment. Risedronate is not metabolized in rat, dog, and human liver preparations. Insignificant amounts (<0.1% of intravenous dose) of drug are excreted in the bile in rats. Therefore, dosage adjustment is unlikely to be needed in patients with hepatic impairment.

Absorption of calcium from calcium carbonate is poor in patients with achlorhydria unless taken with food.

Absorption of calcium from calcium carbonate has not been adequately studied with respect to gender.

There are no clinically significant differences in bioavailability following administration of 1 g elemental calcium as calcium carbonate between young (20 - 27 years) and elderly (63 - 71 years) females.

The effect of race on calcium absorption from oral calcium carbonate has not been studied.

Renal disease affects calcium homeostasis through its effects on vitamin D metabolism, phosphorus excretion, and PTH. Calcium should be administered cautiously to patients with renal disease (creatinine clearance <30 mL/min) to avoid elevations of the calcium-phosphorus ion product (Ca x Phos) and the development of calcinosis.

Treatment and Prevention of Osteoporosis in Postmenopausal Women:

Osteoporosis is characterized by decreased bone mass and increased fracture risk, most commonly at the spine, hip, and wrist.

The diagnosis can be confirmed by the finding of low bone mass, evidence of fracture on x-ray, a history of osteoporotic fracture, or height loss or kyphosis indicative of vertebral fracture. Osteoporosis occurs in both men and women but is more common among women following menopause. In healthy humans, bone formation and resorption are closely linked; old bone is resorbed and replaced by newly-formed bone. In postmenopausal osteoporosis, bone resorption exceeds bone formation, leading to bone loss and increased risk of bone fracture. After menopause, the risk of fractures of the spine and hip increases; approximately 40% of 50 year-old women will experience an osteoporosis-related fracture during their remaining lifetimes. After experiencing 1 osteoporosis-related fracture, the risk of future fracture increases 5-fold compared to the risk among a non-fractured population.

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