Caffeine disposition in the pregnant rabbit. II. Fetal distribution of caffeine and paraxanthine during chronic maternal caffeine administration

Dev Pharmacol Ther. 1988;11(2):118-24.

Abstract

Twenty-three New Zealand White rabbits received a continuous intravenous infusion of caffeine during gestation. The amniotic fluid/maternal plasma concentration ratio was higher for caffeine than for its major metabolite, paraxanthine, throughout gestation, and increased near term for both compounds. Both compounds distributed nearly homogeneously to fluids and tissues of the 29-day fetus, with mean fetal/maternal concentration ratios of 0.7 for paraxanthine and 0.9 for caffeine. The free fraction of caffeine was constant during gestation (about 0.8), while that of paraxanthine increased from 0.25 to 0.4. Similar results were observed in 3 Dutch Belted rabbits given caffeine in their drinking water and sacrificed at 29 days of gestation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Albumins / analysis
  • Amniotic Fluid / analysis
  • Animals
  • Caffeine / administration & dosage
  • Caffeine / blood
  • Caffeine / cerebrospinal fluid
  • Caffeine / pharmacokinetics*
  • Female
  • Fetal Proteins / analysis
  • Fetus / metabolism*
  • Infusions, Intravenous
  • Male
  • Maternal-Fetal Exchange
  • Pregnancy
  • Pregnancy, Animal / metabolism*
  • Protein Binding
  • Rabbits
  • Serum Albumin / analysis
  • Theophylline / blood
  • Theophylline / cerebrospinal fluid
  • Theophylline / pharmacokinetics*
  • Tissue Distribution

Substances

  • Albumins
  • Fetal Proteins
  • Serum Albumin
  • Caffeine
  • Theophylline
  • 1,7-dimethylxanthine