1985 Volume 33 Issue 3 Pages 1187-1194
Salivary excretion of 5-fluorouracil (5-FU) was investigated following bolus intravenous administration (20mg/kg) in four beagle dogs. Parotid (Pr) and mandibular-sublingual saliva (MS) were collected separately by stimulating salivation with 10% citric acid. Significant correlations were observed between 5-FU concentrations in plasma and in each saliva (p<0.01). However, the saliva/plasma drug concentration ratios (S/P ratios) showed fairly large fluctuations (0.472±0.303 for Pr, 0.200±0.196 for MS) and were not influenced by protein concentration in saliva or salivary flow rate. The observed S/P ratios were significantly different from the S/P ratios calculated by the use of Matin's equation which employed the observed salivary pH values and free fraction of 5-FU in plasma and saliva (p<0.001). Therefore, it was concluded that the salivary excretion of 5-FU cannot be explained by pH-partition theory. Total salivary clearance of 5-FU (0.123±0.093ml/min/kg) was less than 0.5% of total body clearance. In each saliva, salivary clearance of 5-FU was almost independent of salivary flow rate. The relationship between salivary clearance and plasma 5-FU concentration is discussed.
