Stereospecific salivary excretion of tocainide enantiomers in man

Saliva and plasma samples collected from four healthy volunteers who had received racemic tocainide by intravenous infusion for 20 minutes were analysed by a stereospecific and sensitive gas chromatographic method. The enantiomeric composition of mixed saliva obtained for a period of 48 hrs have been determined and compared with the corresponding plasma profiles. The concentration of each enantiomer in saliva tended to be greater than those in the corresponding plasma sample, such that the mean saliva to plasma ratio for S(+) tocainide was 2.07 +/- 0.50 (SEM) and for the R(-) isomer 3.683 +/- 0.76 (SEM). Marked intersubject variability was found in the saliva/plasma ratio of both isomers, however, the correlation of saliva/plasma concentrations in each volunteer was good and ranged from r = 0.910 to 0.987 for S(+) tocainide and r = 0.884 to 0.986 for R(-) tocainide. There was a 6-fold difference between saliva and plasma concentration of R(-) isomer in one subject whose saliva pH ranged from 6.9 to 7.1. The difference was only 3.5 fold in another subject whose saliva pH was consistently higher (7.4 to 7.5). Therefore, the saliva/plasma ratio appeared to depend on pH, increasing with decreasing pH. However, the correlation between the saliva/plasma ratio observed and the ratio predicted was poor. Mechanisms other than passive diffusion are likely to be involved in the transfer of tocainide enantiomers from plasma to saliva and are more pronounced with the levo isomer.