Risedronate pharmacokinetics and intra- and inter-subject variability upon single-dose intravenous and oral administration

• Published in: Pharmaceutical research Vol. 18; no. 2; pp. 166 - 170
• Main Authors: MITCHELL, David Y, BARR, William H, EUSEBIO, Rachelle A, STEVENS, Karen A, DUKE, Frank P, RUSSELL, Darrell A, NESBITT, John D, POWELL, James H, THOMPSON, Gary A
• Format: Journal Article
• Language: English
• Published: New York, NY Springer 01.02.2001; Springer Nature B.V
• Subjects: Administration, Oral; Adult; Analysis of Variance; Area Under Curve; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Calcium Channel Blockers - pharmacokinetics; Cross-Over Studies; Etidronic Acid - analogs & derivatives; Etidronic Acid - pharmacokinetics; Female; Humans; Infusions, Intravenous; Male; Medical sciences; Metabolic Clearance Rate; Middle Aged; Pharmacology. Drug treatments; Risedronic Acid; Human; Urine; Intravenous administration; Healthy subject; Single dose; Oral administration; Diphosphonic acid derivatives; Bioavailability; Bisphosphonates; Blood; Blood plasma; Intraindividual comparison; Risedronic acid; Interindividual comparison; Clinical trial; Tablet; Pharmacokinetics
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1023/A:1011024200280

To determine the pharmacokinetics and absolute bioavailability of risedronate after single-dose oral administration of 30 mg risedronate as a tablet and an aqueous solution, and 0.3 mg risedronate as an intravenous infusion. This study was a randomized, three-treatment, four-period, partial replicate crossover study involving 33 healthy volunteers. Treatments were administered 7 weeks apart, and the third treatment was repeated during the fourth period. Serum and urine were collected over 72 hours and 672 hours, respectively. Following intravenous administration, renal clearance accounted for 87% of total clearance, with 65% of the dose excreted within 24 hours and 85% of the dose excreted within four weeks. The absolute bioavailability was approximately 0.62% after both oral formulations, and the relative bioavailability of the tablet compared with the oral solution was 104%. The rate and extent of absorption from the two formulations were bioequivalent based on the range proposed for highly variable drugs. Intrasubject variability following oral administration was 50-80%, and was primarily associated with absorption. The majority of the total clearance after intravenous administration of risedronate was renal clearance, indicating that only a small percentage of a systemic dose is potentially incorporated, or "cleared," into bone. The absolute bioavailability of orally administered risedronate is approximately 0.6%, and is independent of formulation. Variability in the pharmacokinetics following oral administration is primarily associated with intrasubject variability in absorption.