PHARMACOKINETICS OF TALLYSOMYCIN AND BLEOMYCIN IN THE BEAGLE DOG

  • 1 January 1979
    • journal article
    • research article
    • Vol. 63  (11-1) , 1821-1827
Abstract
The pharmacokinetics of tallysomycin, a 3rd-generation bleomycin analog, and bleomycin were determined and compared in the beagle dog. Both compounds exhibited biphasic plasma elimination characteristics and were extensively absorbed after i.m. injection. The elimination half-lives of tallysomycin after i.v. and i.m. administration were 1.51 .+-. 0.41 h and 2.40 .+-. 0.667 h, respectively. These values were longer than the comparable i.v. (1.01 .+-. 0.19 hours) and i.m. (1.12 .+-. 0.39 h) elimination half-lives for bleomycin. The volume of distribution in the central compartment after i.v. administration was 0.111 .+-. 0.039 l/kg for tallysomycin and 0.125 .+-. 0.0723 l/kg for bleomycin. The total apparent volumes of distribution were 0.706 .+-. 0.255 l/kg and 0.388 .+-. 0.245 l/kg for tallysomycin and belomycin, respectively, after i.v. injection. These values were significantly different (P < 0.05). Total urinary recovery in 24 h for tallysomycin was significantly (P < 0.05) less than that for bleomycin after i.v. and i.m. 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.