Salivary excretion of 5-fluorouracil(5-FU). III. Non-linear kinetics of salivary excretion of 5-FU following bolus intravenous administration in rats.

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Abstract
Salivary excretion profiles of 5-fluorouracil(5-FU) were investigated following bolus intravenous administration at three dose levels (12.5, 25, and 50 mg/kg) in rats. Mandibular (M) and parotid (Pr) saliva samples were periodically collected separately via cannulas inserted into the ducts by stimulating salivation with pilocarpine infused intravenously. Simultaneously, salivary pH, flow rate, and protein concentration were determined. (1) Plasma and salive 5-FU concentration decreased bi-exponentially with time. A relatively scattered relationship but a statistically significant correlation was found between each of the saliva concentrations and plasma 5-FU concentration (p < 0.01). (2) The saliva/plasma concentration ratio (S/P ratios) and salivary pH were higher in M than Pr saliva, in contrast to the results in beagle dogs. (3) The S/P ratio and salivary clearance of 5-FU were larger at higher dose, and decreased with the decline of plasma 5-FU concentration, though they showed large fluctuations. It was, therefore, suggested that non-linear kinetics might be involved in the salivary excretion of 5-FU in rats. (4) The contribution of total salivary clearance to total body clearance of 5-FU was found to be insignificant, i.e. less than 0.1% even at the highest dose.