Robert Stanley Ampulski

Clodronate kinetics and bioavailability

Carbon 13–labeled clodronate disodium was given to healthy adult men by intravenous 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; more than 80% of the intravenous dose was recovered within 48 hr. The serum concentration‐time curve over the first 8 hr after intravenous dosing appears biexponential with the disposition phase having a harmonic mean half‐life (t½) of 2 hr. The mean serum clearance was found to be 1.4 ml min−l kg−l and the apparent volume of distribution was approximately 25% of body weight. 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 t½ of 12.8 hr. Thus, 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 hr. Cl2MDP is poorly absorbed with an absolute bioavailability of only 1% to 2%.