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

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 i nfusion. 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 th e fourth period. Serum and urine were collected over 72 hours and 672 hours , respectively. Results. Following intravenous administration, renal clearance accounted fo r 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 w as approximately 0.62% after both oral formulations, and the relative bioav ailability of the tablet compared with the oral solution was 104%. The rate and extent of absorption from the two formulations were bioequivalent base d on the range proposed for highly variable drugs. Intrasubject variability following oral administration was 50-80%, and was primarily associated wit h absorption. Conclusion. The majority of the total clearance after intravenous administr ation of risedronate was renal clearance, indicating that only a small perc entage of a systemic dose is potentially incorporated, or "cleared," into b one. The absolute bioavailability of orally administered risedronate is sim ilar to0.6%, and is independent of formulation. Variability in the pharmaco kinetics following oral administration is primarily associated with intrasu bject variability in absorption.