Pharmacokinetics of tallysomycin and bleomycin in the beagle dog.
The pharmacokinetics of tallysomycin, a third-generation bleomycin analog, and bleomycin have been determined and compared in the beagle dog. Both compounds exhibited biphasic plasma elimination characteristics and were extensively absorbed after in injection. The elimination half-lives of tallysomycin after iv and im administration were 1.51 +/- 0.41 hours and 2.40 +/- 0.667 hours respectively. These values were longer than the comparable iv (1.01 +/- 0.19 hours) and im (1.12 +/- 0.39 hours) elimination half-lives for bleomycin. The volume of distribution in the central compartment after iv administration was 0.111 +/- 0.039 liter/kg for tallysomycin and 0.125 +/- 0.0723 liter/kg for bleomycin. The total apparent volumes of distribution were 0.706 +/- 0.255 liter/kg and 0.388 +/- 0.245 liter/kg for tallysomycin and bleomycin respectively after iv injection. These values were significantly different (P less than 0.05). Total urinary recovery in 24 hours for tallysomycin was significantly (P less than 0.05) less than that for bleomycin after both iv and im injections. These observed differences in pharmacokinetic behavior may, in part, account for differences in in vivo antitumor activities and toxic effects which have been reported for these drugs.
D000818:Animals; D001761:Bleomycin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism*; D004285:Dogs; D005260:Female; D006207:Half-Life; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D007668:Kidney / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate
D001761:Bleomycin