Selective uptake of the anticancer drug bendamustine by liver and kidney tissues following its intravenous administration to mice.
Distribution of 14C-bendamustine following intravenous (i.v.) administration to mice was examined by whole body autoradiographic (WBAR) and quantitative techniques. The WBAR study showed that 14C-bendamustine-derived radioactivity was distributed extremely unevenly at each time interval investigated. After 5 min of administration the highest density of radioactive material was found in the liver and in the kidney. At all time intervals investigated the brain remained free of the label. In a detailed quantitative distribution study it was found that 14C-bendamustine-derived radioactivity was also unevenly distributed throughout the mouse tissues. At 5 min postdosing the level of 14C was by one order higher in the liver and in the kidney in comparison to the lungs, heart, spleen, and muscle. The results of both WBAR and quantitative tissue distribution studies suggest that bendamustine was selectively taken up from the blood by liver and kidney tissues. Because of this pharmacokinetic property, dose modification should be taken into consideration when administering the drug to patients suffering from hepatobiliary and kidney disorders.
Bezek
S
S
Institute of Experimental Pharmacology, Slovak Academy of Sciences, Bratislava, Slovak Republic.
Kukan
M
M
Scasnár
V
V
Lukácsová
M
M
Trnovec
T
T
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D001345:Autoradiography; D000069461:Bendamustine Hydrochloride; D002250:Carbon Radioisotopes; D007275:Injections, Intravenous; D007553:Isotope Labeling; D007668:Kidney / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D009588:Nitrogen Mustard Compounds / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D012015:Reference Standards; D014018:Tissue Distribution; D014915:Whole-Body Counting
D000970:Antineoplastic Agents; D002250:Carbon Radioisotopes; D009588:Nitrogen Mustard Compounds; D000069461:Bendamustine Hydrochloride