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Accumulation of theophylline, theobromine and paraxanthine in the fetal rat brain following a single oral dose of caffeine - PubMed

  • ️Fri Jan 01 1993

Accumulation of theophylline, theobromine and paraxanthine in the fetal rat brain following a single oral dose of caffeine

J M Wilkinson et al. Brain Res Dev Brain Res. 1993.

Abstract

This paper describes the disposition of caffeine and its metabolites, theophylline, theobromine and paraxanthine in the 20-day fetal and adult brains following a single maternal dose of 5 or 25 mg/kg caffeine. Brains and plasma were collected 5 and 30 min, and 1, 3, 8 and 24 h after dosing. It was found that fetal and adult caffeine AUC (area under the concentration-time curve) values did not differ between the brain and plasma at either dose. Caffeine's primary metabolites theophylline, theobromine and paraxanthine did, however, accumulate in the fetal brain at both doses resulting in a 3-fold increase in brain metabolite exposure compared to fetal circulatory levels. In contrast to the fetus, metabolite AUC values after a dose of 25 mg/kg were found to be lower in the brains of adults compared with plasma. This suggests that caffeine's primary metabolites might be selectively excluded from the adult brain. In conclusion we have shown that, unlike the adult, the fetal rat brain accumulates theophylline, theobromine and paraxanthine when exposed to caffeine doses comparable to those attainable by normal human consumption. Since many aspects of caffeine metabolism are similar in the rat and human, we suggested that particular attention should be paid to the consumption of caffeine during pregnancy.

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