Placental transfer and foetal disposition of caffeine and its immediate metabolites in the 20-day pregnant rat: function of dose. 1993

F Abdi, and I Pollard, and J Wilkinson
School of Biological Sciences, Macquarie University, Sydney, New South Wales, Australia.

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.

UI MeSH Term Description Entries
D008431 Maternal-Fetal Exchange Exchange of substances between the maternal blood and the fetal blood at the PLACENTA via PLACENTAL CIRCULATION. The placental barrier excludes microbial or viral transmission. Transplacental Exposure,Exchange, Maternal-Fetal,Exposure, Transplacental,Maternal Fetal Exchange
D010920 Placenta A highly vascularized mammalian fetal-maternal organ and major site of transport of oxygen, nutrients, and fetal waste products. It includes a fetal portion (CHORIONIC VILLI) derived from TROPHOBLASTS and a maternal portion (DECIDUA) derived from the uterine ENDOMETRIUM. The placenta produces an array of steroid, protein and peptide hormones (PLACENTAL HORMONES). Placentoma, Normal,Placentome,Placentas,Placentomes
D011247 Pregnancy The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH. Gestation,Pregnancies
D002110 Caffeine A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes SMOOTH MUSCLE, stimulates CARDIAC MUSCLE, stimulates DIURESIS, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide PHOSPHODIESTERASES, antagonism of ADENOSINE RECEPTORS, and modulation of intracellular calcium handling. 1,3,7-Trimethylxanthine,Caffedrine,Coffeinum N,Coffeinum Purrum,Dexitac,Durvitan,No Doz,Percoffedrinol N,Percutaféine,Quick-Pep,Vivarin,Quick Pep,QuickPep
D005260 Female Females
D005333 Fetus The unborn young of a viviparous mammal, in the postembryonic period, after the major structures have been outlined. In humans, the unborn young from the end of the eighth week after CONCEPTION until BIRTH, as distinguished from the earlier EMBRYO, MAMMALIAN. Fetal Structures,Fetal Tissue,Fetuses,Mummified Fetus,Retained Fetus,Fetal Structure,Fetal Tissues,Fetus, Mummified,Fetus, Retained,Structure, Fetal,Structures, Fetal,Tissue, Fetal,Tissues, Fetal
D006207 Half-Life The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. Halflife,Half Life,Half-Lifes,Halflifes
D000653 Amniotic Fluid A clear, yellowish liquid that envelopes the FETUS inside the sac of AMNION. In the first trimester, it is likely a transudate of maternal or fetal plasma. In the second trimester, amniotic fluid derives primarily from fetal lung and kidney. Cells or substances in this fluid can be removed for prenatal diagnostic tests (AMNIOCENTESIS). Amniotic Fluid Index,Amniotic Fluid Indices,Amniotic Fluids,Fluid Index, Amniotic,Fluid Indices, Amniotic,Fluid, Amniotic,Fluids, Amniotic,Index, Amniotic Fluid,Indices, Amniotic Fluid
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001711 Biotransformation The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alterations may be divided into METABOLIC DETOXICATION, PHASE I and METABOLIC DETOXICATION, PHASE II.

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