Placental transfer of the major caffeine metabolite in the rat using 6-amino-5[N-formylmethylamino]1,3[Me-14C]-dimethyluracil administered orally or intravenously to the pregnant rat
Abstract
6-Amino-5[N-formylmethylamino]1,3[Me-14C]dimethyluracil (1,3,7-DAU), the most important caffeine metabolite in the rat and a minor one in man was synthesized and administered p.o. or i.v. to pregnant rats. This study demonstrates the distribution of this metabolite in the animal and its transfer to the embryos and the fetus. The fetus was shown to be protected by a placental barrier which leads to a lower fetal tissue exposure 1 h after the administration, the equilibrium between fetus and pregnant rat being reached 4-5 h later. Future studies testing the fetotoxicity of this metabolite compared with caffeine must take into consideration that only about half of the oral dose is absorbed. In addition, similar fetal tissue exposure must be obtained when this metabolite is given orally or is produced from caffeine.
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Once caffeine enters the fetal circulation, it is metabolized slowly because neither the placenta nor the fetus itself has cytochrome P450, the enzyme that metabolizes caffeine.
“Once caffeine enters the fetal circulation, it is metabolized slowly because neither the placenta nor the fetus itself has cytochrome P450, the enzyme that metabolizes caffeine (166).”
From The Safety of Ingested Caffeine: A Comprehensive Review (2017) · cites this paper as [166]
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References 15 · Cited by 25
- Authors
- Arnaud, M. J., Bracco, I., Sauvageat, J.-L., & Clerc, M.-F.
- Affiliations
- Nestlé (Switzerland) (CH)
- ORCID
- Arnaud, Maurice J.
- Venue
- Toxicology Letters
- Publisher
- Elsevier BV
- Published
- 1983-05
- Volume
- 16
- Issue
- 3-4
- Pages
- 271-279
- ISSN
- 0378-4274 (ISSN-L)
- OpenAlex
- W1988761521
- Cited by
- 25
- References
- 15
- Citations by year
- 2020: 3 · 2017: 1 · 2015: 3 · 2014: 2 · 2013: 3 · 2012: 1
- FWCI
- 1.93
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Toxicology Letters (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology › Coffee research and impacts
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmacological Effects and Toxicity Studies
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Pregnancy and Medication Impact
- Keywords
- caffeine metabolites, placental transfer, placental barrier, prenatal exposure, pregnancy, oral and intravenous administration, fetal tissue distribution, fetal toxicity, caffeine
- MeSH terms
- Administration, Oral, Animals, Autoradiography, Caffeine, Feces, Female, Injections, Intravenous, Maternal-Fetal Exchange, Pregnancy, Rats, Inbred Strains, Uracil, Rats
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