The pharmacokinetics of the new fluoropyrimidine 5′-deoxy-5-fluorouridine (5′-dFUrd) was investigated in twelve patients. The kinetics of the main metabolite 5-fluorouracil (5-FUra) was studied in eight patients and those of 5,6-dihydro-5-fluorouracil (5-FUraH2) in five patients.

The patients participated in a Phase II study performed to investigate the response rate of 5′-dFUrd in advanced ovarian cancer. The pharmacokinetic data were compared with the clinical effects of the drug. The parent drug and 5-FUra were measured in both plasma and urine by high performance liquid chromatography. 5-FUraH2 concentrations in plasma were determined by capillary gas chromatography using electron capture detection and nitrogen-phosphorus specific detection. Several pharmacokinetic parameters such as elimination half-life, mean residence time, and steady state volumes of distribution are presented for 5′-dFUrd, 5-FUra, and 5-FUraH2.

Two patients showed a partial response, four had stable disease, and five had progressive disease; one patient died due to myelotoxicity. The severity of the side effects correlated with the mean residence times of 5′-dFUrd and 5-FUra. Low pretreatment serum creatinine clearance (due to renal impairment) correlated with low renal excretion of 5′-dFUrd and a long mean residence time of 5′-dFUrd with the sum of observed toxicity. However, the extent of degradation of 5-FUra to 5-FUraH2 may also be related to the severity of the toxicity of 5′-dFUrd.

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