Methylglyoxal-bis(guanylhydrazone) (MGBG; NSC 32946), a competitive inhibitor of S-adenosyl-l-methionine decarboxylase (EC, is currently being reevaluated for its clinical antileukemic activity. MGBG labeled with 14C in the guanylhydrazone moiety was administered i.v. (150 µCi; specific activity, 1.9 µCi/µmol; 20 mg total) to six patients with leukemia. All patients in the study had normal renal and hepatic function. [14C]MGBG underwent no in vivo metabolism; it disappeared from the plasma with an average terminal t½ of 4.1 hr. The 72-hr cumulative urinary excretion was only 14.5 ± 2.2% (S.E. M.) of the total radioactive dose. The apparent volume of distribution was 661 ml/kg and the total clearance rate was 21.2 ml/kg/min. The low urinary excretion rate and the relatively rapid plasma clearance suggest that MGBG may be sequestered in the body. Therefore, if MGBG is adminstered by a frequent treatment schedule, the prolonged biological half-life in humans may significantly contribute to its clinical toxicity.


This work was supported by USPHS National Cancer Institute Contract CM-87185 and Grant CA-09189.

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