[Pharmacokinetics and a phase I study of tegafur-uracil enterogranules in cancer patients]

UFT-E, enterogranules of tegafur-uracil (at molar ratio of 1: 4) was developed in order to minimize GI toxicity of UFT. Pharmacokinetic study after single oral administration of 300 to 1200 mg of UFT-E was carried out in cancer patients measuring tagafur, uracil and 5-FU levels in serum, normal tissue and tumor tissue using HPLC and GC-mass. In the all doses studied, curves of serum tegafur after administration of UFT-E were consistently higher than those of uracil and 5-FU. Peak 5-FU levels were observed at 2-4 hours after administration of UFT-E. Maximum 5-FU levels ranged 0.1-3.0 mcg/ml and were variable in each patient even at the same doses. The serum 5-FU level was correlated with tegafur and uracil levels, especially with the latter. The curves of serum 5-FU of UFT-E were different from those of UFT, and the peak time of UFT-E occurred 2 or 3 hours later than that of UFT and the decrease of 5-FU level was slower. The concentrations of 5-FU in tumor tissue (T) were observed in most of the cases compared with those in normal tissue (N) (T/N ratio of more than 2.0 was observed in 16/23 patients), especially in the patients received higher doses of UFT-E and in the patients with GI cancers. In the phase I study of oral daily consecutive administration of UFT-E in 23 cancer patients, the GI side effects such as anorexia, nausea, vomiting and diarrhea, were observed in 5 out of 23 patientsr.(ABSTRACT TRUNCATED AT 250 WORDS)