Salivary Excretion of Mexiletine after Bolus Intravenous Administration in Analbuminemic Rats

To clarify the effect of plasma albumin on the salivary excretion of mexiletine, we have investigated the kinetics of and correlation between plasma and saliva levels following bolus intravenous administration (5 mg/kg) in male Sprague-Dawley rats (analbuminemic and normal). Parotid and mandibular saliva was collected separately by stimulating salivation with constant rate infusion of pilocarpine (50 μg/kg/min). In both rats, the mexiletine levels in plasma, 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 (p < 0.05 or 0.01), the drug level in parotid saliva was always higher than that in mandibular saliva in both groups (p < 0.05 or 0.01). Furthermore, in both rats, significant correlations were observed when all data relating mexiletine concentration in plasma and saliva were included (p < 0.001). The saliva to plasma drug concentration ratios (S/P ratios) for both saliva in analbuminemic rats (0.814±0.162 for parotid saliva, 0.367±0.074 for mandibular saliva) were higher than those in normal rats (0.727±0.110 for parotid saliva, 0.197±0.061 for mandibular saliva) (p < 0.01). These changes in the S/P ratios between both groups could not be explained by the pH for either parotid or mandibular saliva. In contrast, the slight increase in the unbound fraction of the drug in analbuminemic rats, though it was not significant from the unbound fraction in normal rats, tended to be consistent with the difference in the S/P ratios for both salivary glands. These aspects suggest the possibility that the extent of salivary excretion of mexiletine may be influenced by the albumin concentration and dependent on the unbound fraction in plasma.