Summary
The availability of uridine can alter the sensitivity of tumor cells to antimetabolites such as N-phosphonacetyl-l-aspartic acid (PALA) and acivicin by virtue of the cell's ability to salvage preformed metabolites from its environment. We investigated the pharmacokinetics of physiologically relevant amounts of uridine in cancer patients in a pilot study to further our understanding of uridine metabolism in the human body. Four cancer patients, two males and two females, were given an i.v. bolus of a trace amount of radiolabeled uridine. The nucleoside disappeared from the plasma in a triphasic manner, with initial half-lives of 0.57±0.28 and 1.79±0.62 min and a terminal half-life of 17.5±7.3 min. The volume of distribution was 481±70 ml/kg, and the plasma uridine clearance was calculated to be 1.70±0.42 l/min. Simultaneous plasma and bone marrow uridine concentrations were measured in a separate group of seven healthy volunteers. The uridine concentration in plasma was 2.32±0.58 μM, and that in the bone marrow plasma was 10.44±5.06 μM. These results suggest a very rapid turnover of uridine in the plasma when the nucleoside is present at physiologic concentrations, and that there is a locally high concentration of uridine available for salvage in the bone marrow.
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Supported by grants CA 23334 and CA 23100 from the NCI and a grant from Boehringer Ingelheim Ltd. Presented as an abstract at the American Association for Cancer Research Meeting in Los Angeles, CA, May 7–10, 1986. This research is conducted in part by the Clayton Foundation for Research, California Division. Dr. Howell is a Clayton Foundation Investigator
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Chan, T.C.K., Markman, M., Pfeifle, C.E. et al. Uridine pharmacokinetics in cancer patients. Cancer Chemother. Pharmacol. 22, 83–86 (1988). https://doi.org/10.1007/BF00254188
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DOI: https://doi.org/10.1007/BF00254188