Protein binding effects on salivary excretion of phenobarbital in dogs.

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Abstract
The salivary excretion of phenobarbital was investigated by collecting parotid saliva (Pr) and mandibular-sublingual saliva (MS) separately after i.v. administration in beagle dogs. The alterations in the proportions of saliva secreted by the different glands were produced by salivation stimulants such as citric acid, ascorbic acid, NaCl and sodium glutamate. The phenobarbital concentrations in both Pr and MS were lower than those in plasma. The drug concentrations in MS were significantly lower than in Pr with stimulus of 10% citric acid or 15% NaCl (P < 0.05). There was a significant correlation between phenobarbital concentration in each saliva and plasma specimen (P < 0.05). The stimulation with 10% citric acid produced higher saliva/plasma drug concentration ratios (S/P ratios: 0.923 .+-. 0.175 for Pr, 0.633 .+-. 0.073 for MS) than that with 15% NaCl (S/P ratios; 0.597 .+-. 0.071 for Pr, 0.509 .+-. 0.067 for MS). The S/P ratios were hardly influenced by salivary flow rates. The increased S/P ratios were observed with higher salivary pH, and then the Matin equation seemed to hold for the average values of salivary pH and S/P ratio. The stimulation with 10% citric acid produced higher protein concentration in saliva and higher S/P ratio than that with 15% NaCl following alternate stimulations in the same dog.

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