This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Rosenblum, M. G. Articles by Loo, T. L. Search for Related Content PubMed PubMed Citation Articles by Rosenblum, M. G. Articles by Loo, T. L.

Pharmacokinetics of [¹⁴C]Methylglyoxal-bis(guanylhydrazone) in Patients with Leukemia¹

Department of Developmental Therapeutics, The University of Texas System Cancer Center, M. D. Anderson Hospital and Tumor Institute, Houston, Texas 77030

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 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.

¹ This work was supported by USPHS National Cancer Institute Contract CM-87185 and Grant CA-09189.

² To whom requests for reprints should be addressed.

Received 4/28/80. Accepted 2/ 2/81.

This article has been cited by other articles:

				F. A. L. M. Eskens, G. A. Greim, C. van Zuylen, I. Wolff, L. J. Denis, A. S. Th. Planting, F. A. Muskiet, J. Wanders, N. C. Barbet, L. Choi, et al. Phase I and Pharmacological Study of Weekly Administration of the Polyamine Synthesis Inhibitor SAM 486A (CGP 48 664) in Patients with Solid Tumors Clin. Cancer Res., May 1, 2000; 6(5): 1736 - 1743. [Abstract] [Full Text] [PDF]