Clodronate kinetics and dynamics

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Abstract
Clodronate disodium (Cl2MDP), a drug which reduces osteoclastic bone resorption in amimals and in patients with Paget''s disease, was given i.v. in doses of 3, 6 and 10 mg/kg to 6 men (aged 23-30 yr). Volume of distribution was 0.2720 .+-. 0.0255 1/kg (.hivin.x [mean] .+-. SD) after 3 mg/kg dose, 0.3037 .+-. 0.0445 1/kg after 6 mg/kg and 0.2528 .+-. 0.0417 l/kg after 10 mg/kg. The elimination rate constant was 0.3787 .+-. 0.0546 h-1, 0.3492 .+-. 0.0616 h-1 and 0.3962 .+-. 0.0358 h-1 after 3, 6 and 10 mg/kg, respectively. Corresponding total body clearances were 0.1026 .+-. 0.0149, 0.1049 .+-. 0.0159 and 0.0998 .+-. 0.0172 1/kg per h. Renal clearance accounted for 73% of total body clearance; 73% of the drug was excreted unchanged in the urine in 24 h. 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 were no significant changes in the serum concentration or fractional excretion of Ca, Na 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.

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