Clodronate kinetics and bioavailability

Abstract

13C-labeled clodronate disodium was given to healthy adult men by i.v. infusion and orally in a crossover design. Serum and urine levels were determined as a function of time by isotope-ratio mass spectrometry. Clodronate disodium (Cl2MDP) is primarily excreted unchanged by the kidney; > 80% of the i.v. dose was recovered within 48 h. The serum concentration-time curve over the first 8 h after i.v. dosing appears biexponential with the disposition phase, having a harmonic mean half-life (t1/2) of 2 h. The mean serum clearance was 1.4 ml/min per kg, and the apparent volume of distribution was .apprx. 25% of body wt. Simulations and computer fitting of the cumulative urinary excretion and urinary excretion rates, based on the biexponential serum decay curve, demonstrated the presence of a slow disposition component with a t1/2 of 12.8 h. The disposition kinetics of Cl2MDp appear to be triexponential, although the slowest component is not of major significance after a single dose and could not be verified because of a lack of serum data after 8 h. Cl2MDP is poorly absorbed with an absolute bioavailability of only 1-2%.