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Abstract
1. The dispositions of caffeine and its immediate dimethylxanthine metabolites, theobromine, theophylline and paraxanthine were studied after a single oral dose of 5 and 25 mg/kg caffeine administered to 20-day pregnant and non-pregnant rats, respectively.
2. Peak plasma levels were reached between 1 and 3 h in all fluids and tissues studied.
3. The elimination phase, however, differed significantly between the pregnant and non-pregnant groups. For 25 mg/kg the plasma half-life (t1/2) of caffeine was significantly longer in the pregnant than the non-pregnant group; for 5 mg/kg the elimination rate of caffeine was similar in both groups.
4. AUC values were used to compare caffeine and metabolite exposure in foetal tissues. At 5 mg/kg, peak concentrations for amniotic fluid, foetal blood, liver and kidney were not significantly different from one another. At 25 mg/kg peak levels in foetal liver and kidney were significantly less than those of foetal blood, amniotic fluid or placenta.
5. Because of the observed increase in maternal t1/2 at high dosage, a cautionary note is sounded about caffeine intake in pregnancy.
