Pharmacokinetics of Clodronate after Single Intravenous,Intramuscular and Subcutaneous Injections in Rats

Abstract: The pharmacokinetics of clodronate was studied in rats after single intravenous, intramuscular and subcutaneous doses of a mixture of unlabelled and ¹⁴C-labelled disodium clodronate (25 mg/5 μCi/kg). The peak clodronate concentration in plasma was reached within 5 min., and the drug was eliminated with a half-life of about 1.5 hr regardless of administration route. Bioavailabilities after intramuscular and subcutaneous administration were 105% and 89%, respectively. During the 72 hr collection period, the mean share of clodronate recovered from the urine was about 53% of the dose regardless of administration route. Most of the drug was excreted during the first 24 hr. The amount of clodronate in bone (femur) was 186 μg/g tissue at 2 hr after intravenous administration, 188 μg/g after intramuscular administration and 157 μg/g after subcutaneous administration. It is concluded that absorption of clodronate after intramuscular and subcutaneous administration is rapid and good, and that the concentrations of the drug in bone after 2 hr are about the same as after intravenous administration.