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  • Title: The tissue distribution of clodronate (dichloromethylene bisphosphonate) in mice. The effects of vehicle and the route of administration.
    Author: Mönkkönen J, Ylitalo P.
    Journal: Eur J Drug Metab Pharmacokinet; 1990; 15(3):239-43. PubMed ID: 2147646.
    Abstract:
    Clodronate (dichloromethylene bisphosphonate) accumulates extensively in bone by binding to hydroxyapatite crystals. In an hypo-osmotic vehicle, it accumulates also in the spleen and, to a lesser extent, in the liver of mice and rats. In the present study, the effects of parenteral routes of administration (intravenous, intraperitoneal, and subcutaneous), drug dose, and injection vehicle on the distribution of [14C]-clodronate were studied in mice. The route of drug injection had no effect on the deposition of clodronate in bone. Either deionized water or iso-osmotic saline used as vehicles for intravenous administration of the drug caused equal and dose-dependent accumulation in bone. In iso-osmotic glucose, however, the osseous deposition of the drug was 2.2-2.5 times lower than in the other vehicles (water, saline, choline chloride). Clodronate accumulated in spleen and liver only after intravenous injection when the drug was in hypo-osmotic vehicle, and the process was saturable at high doses. The hypotonic vehicle probably causes a local hemolysis, and clodronate forms complexes with erythrocyte iron, which is a prerequisite for ingestion of the drug by splenic and hepatic macrophages.
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