Summary.-Concentrations of 5-fluorouracil (FU) were measured in the plasma of patients receiving i.v. infusions of the drug for 5 days as treatment for adenocarcinoma of the gastrointestinal tract. Concentrations of FU varied widely in many patients. Concentration of drug x time of infusion (C x t values) were calculated.Patients showing a partial response or stabilization of disease had significantly higher C x t values than non-responders. Methyl CCNU did not affect the C x t values of FU. Determination of the plasma concentration of FU would allow the dose of the drug to be adjusted to maintain high concentrations of FU in the plasma. Our data suggest that such high concentrations would increase the response rate in this disease.

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A gas chromatographic-mass spectrometric method was developed for determining 5-fluorouracil in plasma, using methylated thymine as an internal standard. 2 5-fluorouracil was extracted from plasma by a novel procedure which removed plasma components interfering with the sensitivity of the assay. The method included heating the plasma, washing with ether and extracting the drug under optimum conditions. 3 The sensitivity of the assay was 10 ng/ml plasma, sufficient to determine the low concentrations of 5-fluorouracil found in plasma during continuous infusion of the drug in patients receiving chemotherapy for cancer.

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