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Cancer Chemotherapy and Pharmacology

, Volume 8, Issue 1, pp 119–123 | Cite as

Pharmacokinetics and metabolism of β-2′-deoxythioguanosine and 6-thioguanine in man

  • Katherine Lu
  • John A. Benvenuto
  • Gerald P. Bodey
  • Jeffrey A. Gottlieb
  • Michael G. Rosenblum
  • Ti Li Loo
Original Articles Pharmacokinetics, TG, β-TGdR, Metabolism

Summary

Resistance to the antileukemic agent 6-thioguanine (TG) inevitably develops in animal tumors. However, a new agent, β-2′-deoxythioguanosine (β-TGdR) can overcome TG resistance in animal tumor models and is therefore of potential clinical use. The pharmacokinetics of radiolabeled TG were compared with those of β-TGdR in patients with cancer after intravenous administration. [35S]-β-TGdR (5.4 mg/kg, 200 mg/m2, 200 μCi total) was administered to five patients; the radiolabel in the plasma declined with an initial half-life (t1/2) of 14 min and a terminal t1/2 of 19.3 h. Within 24 h, 65% of the radiolabel was excreted in the urine. In contrast, after administration of [35S]-6-TG (3.4 mg/kg, 125 mg/m2, 200 μCi total) the average initial t1/2 was 40 min while the terminal phase t1/2 was 28.9 h. Urinary excretion of the radiolabel was 75% of the dose 24 h after administration. Both thiopurines were rapidly and extensively degraded and excreted as 6-thioxanthine, inorganic sulfate, S-methyl-6 thioxanthine, and 6-thiouric acid in addition to other products. Small amounts of unchanged drug were also excreted. These studies suggest that β-TGdR is merely a latent form of TG.

Keywords

Sulfate Cancer Research Intravenous Administration Urinary Excretion Tumor Model 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer-Verlag 1982

Authors and Affiliations

  • Katherine Lu
    • 1
  • John A. Benvenuto
    • 1
  • Gerald P. Bodey
    • 1
  • Jeffrey A. Gottlieb
    • 1
  • Michael G. Rosenblum
    • 1
  • Ti Li Loo
    • 1
  1. 1.Department of Developmental Therapeutics, The University of Texas System Cancer CenterMD Anderson Hospital and Tumor InstituteHoustonUSA

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