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Abstract
1. Caffeine disposition was studied over 24 h in rats on the 12th day of pregnancy given 80 mg/kg of drug as a single oral dose or in four divided doses every three hours.
2. Peak blood levels of caffeine were reached at three hours after the single dose, and at 10 h (at half the previous value) after the first of the divided doses.
3. At the end of the experiment both caffeine and its dimethylxanthine metabolites were higher in blood, amniotic fluid and fetuses after divided doses than after the single dose. Urinary excretion over 24 h was the same for the two groups.
4. The overall conclusions underline that caffeine per se and not its metabolites are responsible for the teratogenic effects.