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Clin Pharmacol Ther. 1982 Mar;31(3):402-10.

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 (Cl2/MDP) is primarily excreted unchanged by the kidney; more than 80% of the intravenous dose was recovered within 48 hr. The serum concentrations-time curve over the first 8 hr after intravenous dosing appears biexponential with the disposition phase having a harmonic mean half-life (t 1/2) of 2 hr. The mean serum clearance was found to be 1.4 ml min-1 kg-1 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 t 1/2 of 12.8 hr. Thus, the disposition kinetics of Cl2MDP appear to be triexponentials, 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%.

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