caa a22 4500 465812252 CHVBK 20180323112119.0 cr unu---uuuuu 170327e19900701xx s 000 0 eng 10.1007/BF03190210 doi (NATIONALLICENCE)springer-10.1007/BF03190210 The tissue distribution of clodronate (dichloromethylene bisphosphonate) in mice. The effects of vehicle and the route of administration [Elektronische Daten] [J. Mönkkönen, P. Ylitalo] Summary: 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. Springer-Verlag, 1990 Clodronate (dichloromethylene bisphosphonate) nationallicence distribution nationallicence spleen nationallicence liver nationallicence bone nationallicence Mönkkönen J. Department of Pharmacology and Toxicology, University of Kuopio, P.O. Box 6, SF-70211, Kuopio, Finland aut Ylitalo P. Department of Pharmacology and Toxicology, University of Kuopio, P.O. Box 6, SF-70211, Kuopio, Finland aut European Journal of Drug Metabolism and Pharmacokinetics Springer-Verlag 15/3(1990-07-01), 239-243 0378-7966 15:3<239 1990 15 13318 https://doi.org/10.1007/BF03190210 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF03190210 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Mönkkönen J. Department of Pharmacology and Toxicology, University of Kuopio, P.O. Box 6, SF-70211, Kuopio, Finland aut NATIONALLICENCE 700 1- Ylitalo P. Department of Pharmacology and Toxicology, University of Kuopio, P.O. Box 6, SF-70211, Kuopio, Finland aut NATIONALLICENCE 773 0- European Journal of Drug Metabolism and Pharmacokinetics Springer-Verlag 15/3(1990-07-01), 239-243 0378-7966 15:3<239 1990 15 13318 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer