Possible prediction of adverse reactions to pyrimidine chemotherapy from urinary pyrimidine levels and a case of asymptomatic adult dihydropyrimidinuria.

Deficiency of dihydropyrimidine dehydrogenase or dihydropyrimidinase, enzymes that catalyze the breakdown of pyrimidine chemotherapy agents such as 5-fluorouracil, may cause serious adverse reactions to these agents. We attempted to establish the reference range for urinary pyrimidines in adults to detect individuals with abnormal pyrimidine metabolism. We analyzed urinary pyrimidine levels in 1133 adults to establish a reference range for persons ages 20 years or older. Urinary dihydrouracil and uracil levels were determined by high-performance liquid chromatography with column switching. The reference range obtained was found to be 0-59.3 micromol/g creatinine for dihydrouracil and 0-129.8 micromol/g creatinine for uracil. In addition, an asymptomatic man with suspected dihydropyrimidinase deficiency was detected on the basis of dihydropyrimidinuria. Although only three cases of this disease have been found worldwide, including one infant reported previously by our group, it may not be so rare as has been thought. In this man, a 10 mg/kg oral uracil loading test yielded a peak blood dihydrouracil level of 192.1 micromol/liter and a peak uracil level of 67.8 micromol/liter. Eight h after loading, the uracil level was still 11.1 micromol/liter, about 17 times that in healthy subjects. Additional research on dihydropyrimininase deficiency may help to prevent adverse reactions to pyrimidine chemotherapy agents in susceptible individuals.