Placental transfer and foetal disposition of caffeine and its immediate metabolites in the 20-day pregnant rat: function of dose.
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.
Abdi
F
F
School of Biological Sciences, Macquarie University, Sydney, New South Wales, Australia.
Pollard
I
I
Wilkinson
J
J
D000653:Amniotic Fluid / Q000378:metabolism; D000818:Animals; D001711:Biotransformation; D002110:Caffeine / Q000378:metabolism / Q000493:pharmacokinetics*; D005260:Female; D005333:Fetus / Q000378:metabolism*; D006207:Half-Life; D008431:Maternal-Fetal Exchange; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D014970:Xanthines / Q000097:blood / Q000378:metabolism
D014970:Xanthines; D002110:Caffeine