Actonel Clinical Pharmacology

Drug Library
Actonel - Clinical Pharmacology [Risedronate]

Distribution:

The mean steady-state volume of distribution is 6. 3 L/ kg in humans. Human plasma protein binding of drug is about 24%. Preclinical studies in rats and dogs dosed intravenously with single doses of [ 14 C] risedronate indicate that approximately 60% of the dose is distributed to bone. The remainder of the dose is excreted in the urine. After multiple oral dosing in rats, the uptake of risedronate in soft tissues was in the range of 0.001% to 0. 01%.

Metabolism:

There is no evidence of systemic metabolism of risedronate.

Elimination:

Approximately half of the absorbed dose is excreted in urine within 24 hours, and 85% of an intravenous dose is recovered in the urine over 28 days. Mean renal clearance is 105 mL/ min (CV = 34%) and mean total clearance is 122 mL/ min (CV = 19%), with the difference primarily reflecting nonrenal clearance or clearance due to 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. 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:

Pediatric:

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

Gender:

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

Geriatric:

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

Race:

Pharmacokinetic differences due to race have not been studied.

Renal Insufficiency:

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