Interaction of a caffeine overdose with clinical doses of contraceptive ethinyl estradiol in a young woman

Aim

The overdose of caffeine, a cytochrome P450 1A2 probe, in young women has become a problem. The aim of this study was to evaluate possible drug interactions between intentionally overdosed caffeine (12 g) and oral contraceptive doses of ethinyl estradiol prescribed to a young woman in a suicide attempt.

Methods

The serum concentrations of caffeine in the patient and the time-dependent ethinyl estradiol inhibition of caffeine oxidation in vitro were evaluated.

Results

The serum concentration of caffeine 4 h after overdose was 136 μg/mL; from the data obtained between 4 and 28 h after overdose, the half-life was estimated to be 33 h, which is many times larger than the normal value. Prescribed ethinyl estradiol prolonged caffeine elimination in vivo and inhibited paraxanthine formation, as evidenced by the low serum concentrations. In human liver microsomes, ethinyl estradiol (50 nM) inhibited half of caffeine N₃-demethylation. Pre-incubation of human liver microsomes with ethinyl estradiol resulted in a powerful time-dependent inhibitory effect on caffeine N₃-demethylation in human liver microsomes.

Conclusion

These results suggest that a prescription history of contraceptives at clinical doses may have a strong effect on the pharmacokinetics of overdosed caffeine in young women, resulting in dangerous drug interactions.