PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
RCT Entities:
PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
Authors: D Y Mitchell; R A Eusebio; N A Sacco-Gibson; K A Pallone; S C Kelly; J D Nesbitt; C P Brezovic; G A Thompson; J H Powell Journal: J Clin Pharmacol Date: 2000-03 Impact factor: 3.126
Authors: S T Harris; N B Watts; H K Genant; C D McKeever; T Hangartner; M Keller; C H Chesnut; J Brown; E F Eriksen; M S Hoseyni; D W Axelrod; P D Miller Journal: JAMA Date: 1999-10-13 Impact factor: 56.272
Authors: S A Khan; J A Kanis; S Vasikaran; W F Kline; B K Matuszewski; E V McCloskey; M N Beneton; B J Gertz; D G Sciberras; S D Holland; J Orgee; G M Coombes; S R Rogers; A G Porras Journal: J Bone Miner Res Date: 1997-10 Impact factor: 6.741
Authors: G J Yakatan; W J Poynor; R L Talbert; B F Floyd; C L Slough; R S Ampulski; J J Benedict Journal: Clin Pharmacol Ther Date: 1982-03 Impact factor: 6.875
Authors: Kenneth C Lasseter; Arturo G Porras; Andrew Denker; Anu Santhanagopal; Anastasia Daifotis Journal: Clin Drug Investig Date: 2005 Impact factor: 2.859