Pharmacokinetics of [14C]methylglyoxal-bis-guanylhydrazone) in patients with leukemia.

Abstract

Methylglyoxal-bis(guanylhydrazone) (MGBG; NSC 32946), a competitive inhibitor of S-adenosyl-L-methionine decarboxylase (EC 4.1.1.50), currently being reevaluated for its clinical antileukemic activity. MGBG labeled with 14C in the guanylhydrazone moiety was administered i.v. (150 microCi; specific activity, 1.9 microCi/mumol; 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 1/2 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 administered by a frequent treatment schedule, the prolonged biological half-life in humans may significantly contribute to its clinical toxicity.

• Authors: M G Rosenblum, M J Keating, B S Yap, T L Loo
• Journal: Cancer research (Cancer Res) Vol. 41 Issue 5 Pg. 1748-50 (May 1981) ISSN: 0008-5472 [Print] United States
• PMID: 7214342 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Guanidines
• Mitoguazone

Topics

• Drug Evaluation
• Guanidines (metabolism)
• Humans
• Kinetics
• Leukemia (drug therapy)
• Metabolic Clearance Rate
• Mitoguazone (metabolism, therapeutic use, urine)