The influence of structure on the accumulation of caffeine induced by methyl xanthine derivatives.

In rats given caffeine (25 mg kg-1 p.o.) and 1,3,8-trisubstituted xanthine (1,3,8-TSX) derivatives (10 mg kg-1 p.o.) the accumulation of the former in plasma was 300% higher than that in control animals given caffeine alone. The effect on caffeine accumulation appears to be independent of the nature of the N3 substituent and its absence in rats given 1,3-disubstituted xanthines (1,3-DSX) instead of 1,3,8-TSX suggests that the presence of the C8-methyl group in the latter compounds is responsible for the accumulation phenomenon. The results of our previous work imply that these observations in this rat model can be extrapolated to man.