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%.
D000284:Administration, Oral; D000328:Adult; D001682:Biological Availability; D002247:Carbon Isotopes; D004002:Clodronic Acid / Q000008:administration & dosage / Q000378:metabolism*; D004164:Diphosphonates / Q000008:administration & dosage / Q000378:metabolism*; D006801:Humans; D006843:Hydrocarbons, Chlorinated / Q000378:metabolism*; D007263:Infusions, Parenteral; D007700:Kinetics; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D008752:Methylene Chloride / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000378:metabolism*; D008954:Models, Biological; D011897:Random Allocation
D002247:Carbon Isotopes; D004164:Diphosphonates; D006843:Hydrocarbons, Chlorinated; D004002:Clodronic Acid; D008752:Methylene Chloride