Salivary excretion of 5-fluorouracil (5-FU). V. Effect of 5-FU concentration in perfusate on the salivary excretion of 5-FU in perfused rat mandibular gland

The effect of 5-fluorouracil (5-FU) concentration in the perfusate on the salivary excretion of 5-FU was investigated in the rat mandibular gland perfused with modified Ringer solution containing pilocarpine (10 microM). The saliva to venous-effluent concentration ratio (S/E ratio) of 5-FU increased gradually during the perfusion. The 5-FU concentration in the perfusate ranging from 10 to 200 micrograms/ml caused elevation in the mean value of S/E ratio. This non-linearity suggested that the present perfusion method would be useful to further investigation for the mechanism of salivary excretion of 5-FU, since the tendency of the non-linearity was similar to that in in vivo studies as reported previously. The salivary flow rate declined with time, and the greater mean value of the flow rate was obtained during perfusion with the perfusate containing the lower level of 5-FU. Statistically significant correlation was found between the S/E ratio of 5-FU and salivary flow rate (p less than 0.01). Therefore, in the perfused rat mandibular gland, it was concluded that 5-FU itself had an influence on the salivary excretion of 5-FU via decreasing salivary flow rate. On the other hand, the salivary clearance of 5-FU showed no distinct increase and/or decrease not only with time but also with the change of 5-FU concentration in the perfusate. It seems to result from the cancellation of the increased S/E ratio of 5-FU by the decreased salivary flow rate in perfused rat mandibular gland.