Clodronate kinetics and dynamics.

Clodronate disodium (Cl2MDP) was given intravenously in doses of 3, 6 and 10 mg/kg to six men (aged 23 to 30 yr). Volume of distribution was 0.2720 +/- 0.0255 l/kg (mean +/- SD) after 3 mg/kg dose, 0.3037 +/- 0.0445 l/kg after 6 mg/kg, and 0.2528 +/- 0.417 l/kg after 10 mg/kg. The elimination rate constant was 0.3787 +/- 0.0546 hr(-1), 0.3492 +/- 0.0616 hr(-1), adn 0.3962 +/- 0.0358 hr(-1) after 3, 6, and 10 mg/kg. Corresponding total body clearances were 0.1026 /+- 0.0149, 0.1049 +/- 0.0159, and 0.0998 +/- 0.0172 l/kg/hr. Renal clearance accounted for 73% of total body clearance; 73% of the drug was extracted unchanged in the urine in 24 hr. After Cl2MDP serum phosphate decreased approximately 13%; this was associated at the 10 mg/kg dose with a transient fall in fractional phosphate excretion. There was no significant changes in the serum concentration of fractional excretion of calcium, sodium, or uric acid. Creatinine clearance and renal concentrating ability were not altered by Cl2MDP. After short-term administration Cl2MDP is excreted primarily by the kidney but has no significant effects on renal function.