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 a gents, We attempted to establish the reference range for urinary pyrim idines in adults to detect individuals with abnormal pyrimidine metabo lism, We analyzed urinary pyrimidine levels in 1133 adults to establis h a reference range for persons ages 20 years or older, Urinary dihydr ouracil and uracil levels were determined by high-performance liquid c hromatography with column switching, The reference range obtained was found to be 0-59.3 CLmoVg creatinine for dihydrouracil and 0-129.8 mu mol/g creatinine for uracil, In addition, an asymptomatic man with sus pected dihydropyrimidinase deficiency was detected on the basis of dih ydropyrimidinuria. Although only three cases of this disease have been found worldwide, including one infant reported previously by our grou p, 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 1 92.1 mu mol/liter and a peak uracil level of 67.8 mu mol/liter. Eight h after loading, the uracil level was still 11.1 mu mol/liter, about 1 7 times that in healthy subjects. Additional research on dihydropyrimi ninase deficiency may help to prevent adverse reactions to pyrimidine chemotherapy agents in susceptible individuals.