A critical step in the pathway of DNA synthesis is the production of thymidylate from deoxyuridine monophosphate. This reaction is catalyzed by the enzyme thymidylate synthase (TS). Zeneca ZD9331 is a folate analogue and TS inhibitor intended for the treatment of solid human tumors. The toxic effects of the compound should be more predictable, manageable, or both than the earlier compound, raltitrexed, giving it several important advantages as an anti-neoplastic agent. This study will examine the bioavailability, pharmacokinetics, and tolerability of Zeneca ZD9331 given as an oral tablet to adult subjects with refractory solid malignancies.
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