Fluorouracil Dipyridamole

Grem, JL, Mulcahy T, Miller EM, et al. Interaction of deoxyuridine with fluorouracil and dipyridamole in a human colon cancer cell line. Biochem Pharmacol 1989 38 51-59. 

The pharmacokinetics of fluorouracil have been studied with escalating doses as a 72-hour intravenous infusion alone or in combination with a fixed dose of dipyridamole, a nucleoside transport inhibitor, and an enhancer of fluorouracil cytotoxicity (143). Stomatitis was dose-limiting at a fluorouracil dose of 2300 mg/m /day. For courses... 

Remick SC, Grem JL, Fischer PH, Tutsch KD, Alberti DB, Nieting LM, Tombes MB, Bruggink J, Willson JK, Trump DL. Phase I trial of 5-fluorouracil and dipyridamole administered by seventy-two-hour concurrent continuous infusion. Cancer Res 1990 50(9) 2667-72. 

Grem JL. Biochemical modulation of fluorouracil by dipyridamole preclinical and clinical experience. Semin Oncol 1992 19 56-65. 

One study suggested that intravenous dipyridamole may reduce the steady-state plasma levels of fluorouracil, whereas others found that oral dipyridamole caused no important changes in fluorouracil pharmacokinetics. 

An alternative mechanism may involve an inhibition of nucleoside transport. It has been shown that S-acetylamidobenzamide inhibits adenosine transport, and we have shown that SAB inhibits thymidine transport (unpublished results). This would explain the differential effect of SAB on purine base and nucleoside cytotoxicity. Grem and Fischer (17) observed that nucleoside transport inhibitors enhanced the cytotoxicity of 5 fluorouracil by preventing efflux of 5 -fluorodeoxyuridine. Since purine base analogues can be interconverted to the nucleoside derivatives, a similar mechanism could apply for the potentiation of 6TG by SAB. However in this case, we might expect to see an enhancement of 6TG cytotoxicity by dipyridamole, which is not seen. 

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