PHARMACOKINETICS, TISSUE DISTRIBUTION AND BILIARY-EXCRETION OF FT-ADM AFTER INTRAVENOUS ADMINISTRATION OF DA-125, A PRODRUG OF FT-ADM TO DOGS - A NEW ADRIAMYCIN ANALOG CONTAINING FLUORINE

The pharmacokinetic parameters, tissue distribution and biliary excretion of M1-M4 were estimated after intravenous (i.v.) administration of DA-125, 2.5 mg per kg to beagle dogs. The mean values of the terminal half-life, mean residence time, total body clearance and apparent volume of distribution at steady state of M1 were 266 min, 170 min, 61.3 ml min(-1) kg(-1) and 9500 ml kg(-1), respectively (four male and four female dogs). M1 was highly concentrated in lung (five male and five female dogs), and this probably means that lung tumors are subjected to greater exposure to M1, an active metabolite of DA-125. The 8 h biliary excretion of M2 was significantly greater than that of M1, 53.6 vs 6860 pg (three male and two female dogs). The amount of glucuronide and/or sulfate conjugates of M1-M4 in the bile sample was negligible.