• Corpus ID: 25335283

Pharmacokinetic/pharmacodynamic study of ZD9331, a nonpolyglutamatable inhibitor of thymidylate synthase, in a murine model following two curative administration schedules.

  title={Pharmacokinetic/pharmacodynamic study of ZD9331, a nonpolyglutamatable inhibitor of thymidylate synthase, in a murine model following two curative administration schedules.},
  author={G. Wynne Aherne and Anthea Hardcastle and Erica N. Ward and Donna Dobinson and Thomas Roy Crompton and Melanie Valenti and Lisa Brunton and Ann L. Jackman},
  journal={Clinical cancer research : an official journal of the American Association for Cancer Research},
  volume={7 9},
  • G. Aherne, A. Hardcastle, A. Jackman
  • Published 1 September 2001
  • Biology, Medicine, Chemistry
  • Clinical cancer research : an official journal of the American Association for Cancer Research
ZD9331 is a nonpolyglutamatable antifolate inhibitor of thymidylate synthase currently in clinical development. This enzyme is crucial for DNA synthesis and catalyzes the reductive methylation of dUMP to form thymidylate, which is subsequently converted to dTTP. The pharmacokinetics of two curative antitumor doses of ZD9331 administered by either a single i.p. bolus injection (50 mg/kg) or by 24-h s.c. infusion (3 mg/kg) have been measured in a thymidine salvage-incompetent murine lymphoma… 

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