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  • Title: Disposition and metabolism of adriamycin octanoylhydrazone (NSC 233853) in mice and rabbits.
    Author: Egorin MJ, Clawson RE, Ross LA, Chou FT, Andrews PA, Bachur NR.
    Journal: Drug Metab Dispos; 1981; 9(3):240-5. PubMed ID: 6113933.
    Abstract:
    The disposition, metabolism, and excretion of adriamycin octanoylhydrazone (OctAdr) were studied after iv administration to BALB/c mice and New Zealand White rabbits and were compared to similar studies of adriamycin (Adr). In mice, concentrations of OctAdr-derived fluorescence were initially greatest in lung with very low concentrations detectable in kidney, liver, and spleen. Little drug fluorescence was found in brain, heart, or skeletal muscle. Adriamycin had the highest drug fluorescence concentration in the kidney, with progressively lower but easily detectable concentrations in liver, heart, lung, spleen, and skeletal muscle. Drug fluorescence was lost much more rapidly from tissues of mice injected with OctAdr than from tissues of mice injected with Adr. At all times after injection, Adr was the major fluorescent drug species recovered from livers and kidneys of mice treated with OctAdr or Adr, although substantial amounts of unaltered OctAdr were recovered from the former group. In rabbits, plasma concentrations of OctAdr-derived fluorescence declined rapidly but then remained relatively constant from 120 to 480 min after injection. No OctAdr-derived fluorescence was observed in urine. During the 8 hr after injection, biliary excretion of OctAdr represented approximately 25% of the administered dose. At all times after injection, OctAdr was the major biliary fluorescent species, with Adr and adriamycinol (Adrol) the second and third most prominent, respectively. Eight hours after OctAdr administration, lung contained the highest concentration of drug-related fluorescence, with progressively lower amounts in liver, kidney, duodenum, and heart. Brain, skeletal muscle, and spleen contained little or no OctAdr-derived fluorescence. Adr and OctAdr were the major fluorescent species in all tissues. Small amounts of Adrol were detected in all tissues, but aglycones were present only in liver.
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