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Salivary excretion profiles of 5-fluorouracil (5-FU) were investigated following simultaneous bolus intravenous injection of a loading dose and constant-rate intravenous infusion of a maintenance dose of at one of three dose levels in rats. By stimulating salivation with pilocarpine infused intravenously, mandibular (M) and parotid (Pr) saliva samples were periodically collected separately via cannulas inserted into the ducts. Simultaneously, salivary pH and salivary flow rate were determined. (1) There was a good correlation between plasma concentration and each of the saliva concentrations of 5-FU with regard to the pooled data of the three doses (p less than 0.01). (2) A gland type difference between M and Pr in the saliva/plasma concentration ratio (S/P ratio) of 5-FU was observed. This difference seemed to result from that in salivary pH. These findings were similar to the results following bolus intravenous administration of 5-FU in rats. (3) The fluctuations of the S/P ratio and salivary clearance of 5-FU were smaller than those following the bolus intravenous administration. (4) The S/P ratio and salivary clearance were larger at higher dose and higher plasma concentration of 5-FU. It was confirmed that non-linear kinetics might be involved in the salivary excretion of 5-FU in rats, and it was speculated that 5-FU excreted into primary saliva might be reabsorbed partly through some saturable process.

journal of pharmacobio-dynamics

Salivary excretion of 5-fluorouracil (5-FU). IV. Dependency of saliva/plasma concentration ratio and salivary clearance on plasma concentration of 5-FU during constant-rate intravenous infusion in rats.