Salivary excretion of mexiletine after bolus intravenous administration in rats

Abstract— Salivary excretion of mexiletine was investigated following bolus intravenous administration (10 mg kg−1) in rats. Parotid and mandibular saliva was collected separately by stimulating salivation with constant rate infusion of pilocarpine (3 mg kg−1 h−1). The mexiletine levels in blood plasma and parotid and mandibular saliva declined biexponentially with time in almost parallel fashion. Although the mexiletine levels in both types of saliva were lower than that in plasma, the drug level in parotid saliva was always higher than that in mandibular saliva. Significant correlations were observed when all data relating mexiletine concentration in plasma and saliva were included (P < 0·001). The saliva/plasma drug concentration ratios (S/P ratios) did not vary to a large extent (0·56 ± 0·10 for parotid saliva, 0·21 ± 0·06 for mandibular saliva), but there was a consistent tendency for the higher plasma drug levels in the distribution phase to produce relatively high S/P ratios for both parotid and mandibular saliva. Moreover, the plasma mexiletine levels calculated by the equation of Matin et al (1974) employing the observed values for the saliva drug level, saliva pH and free fraction of mexiletine in plasma were significantly higher than the observed drug levels. Therefore, it is suggested that the salivary excretion of mexiletine could not be explained quantitatively by simple, passive secretion based on pH‐partition theory.