Pharmacokinetics of Caffeine and Dimethylxanthines in Plasma and Saliva

The concentrations of caffeine and its metabolites, dimethylxanthines, in the plasma and saliva were determined in order to clarify the metabolic capacity of caffeine in pregnant women. After taking caffeine-free diet for 3 d, caffeine (3 mg/kg) was orally administered to 6 healthy volunteers. The concentrations of caffeine and dimethylxanthines, i.e. theobromine, paraxanthine and theophylline in the plasma and saliva were measured. The concentrations in the saliva showed positive relationships to those in the plasma for both caffeine and paraxanthine. There was a linear relationship between the plasma clearance of caffeine and the molar concentration ratio of paraxanthine to caffeine in the saliva at 6 h after oral administration of caffeine. The concentration of caffeine in the saliva from pregnant women was higher than 1.3 μg/ml at 1 h after taking one or three cups of coffee or green tea without restriction. These results indicate that the plasma levels of caffeine and paraxanthine can be predicted from the saliva levels of caffeine and paraxanthine. Moreover, it would be possible to estimate the plasma clearance or metabolic capacity of caffeine from the molar concentration ratio of paraxanthine to caffeine in the saliva.