OCULAR SIDE-EFFECTS WITH 5-FLUOROURACIL

The concentrations of 5-fluorouracil in tears and plasma were studied in 8 patients receiving the drug for carcinoma of the colon. The drug was measured by a GLC method and was present only in the tears of patients with excessive lacrimation. In 3 patients with watery eyes the peak concentration in tears (16-23.8 .mu.g/ml) occurred 15 min after i.v. administration and this corresponded with the end of the distribution (.alpha.) phase in the plasma when the plasma levels ranged 18-26 .mu.g/ml. In 5 patients without eye symptoms the drug was undetectable in the lacrimal fluid even though they had similar plasma levels (15-25 .mu.g/ml) of 5-fluorouracil. The volumes of distribution and plasma clearance rates were similar in the 2 groups [being 0.2-0.52 (mean = 0.33) 1/kg and 612-978 (mean = 850) ml/min, respectively, in patients with excessive lacrimation and 0.13-0.79 (mean = 0.36) 1/kg and 435-1138 (mean = 831) ml/min, respectively, in the 5 patients without symptoms.]. 5-Fluorouracil apparently produces irritation of the lacrimal apparatus in about 30% of patients on the drug and in association with this appears in the tears where it may be responsible for the reported irritation and fibrosis of the tear duct.