Pharmacokinetics of [¹⁴C]Methylglyoxal-bis(guanylhydrazone) in Patients with Leukemia

Methylglyoxal-bis(guanylhydrazone) (MGBG; NSC 32946), a competitive inhibitor of S-adenosyl-L-methionine decarboxylase (EC 4.1.1.50), 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 t_1/2of 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.