Reasons for intraindividual inconstancy of the digoxin saliva to serum concentration ratio

When a constant dose of digoxin was administered orally over several days, the digoxin concentration in saliva and erythrocytes rose faster than in serum. Thus, the saliva/serum concentration ratio was below 1.0 after a single dose and above 1.0 in the steady state. The digoxin concentration was relatively high in "unstimulated" (more or less spontaneous) saliva and decreased with stimulation of the salivary flow rate. It therefore appeared that the actual salivary digoxin concentration depended on 2 components: the digoxin concentration in "stimulated" saliva depended only on the rapid diffusion from the blood into saliva, and the concentration in the "unstimulated" saliva depended on the rapid diffusion and on a slower exchange with the intracellular compartment. It is suggested that unstimulated saliva reflects the intracellular digoxin concentration and stimulated saliva reflects the free digoxin concentration of the serum. Both effects must be taken in account when interpreting the saliva/serum ratio, and they may explain conflicting results in the literature.