ArticlePharmacological reports : PR2025
Paracetamol, its metabolites, and their transfer between maternal circulation and fetal brain in mono- and combination therapies.
Article in Pharmacological reports : PR, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- A Noisy Signal? Geographic Bias in FAERS Reports Linking Paracetamol to Autism Spectrum Disorder.Journal of clinical medicine · 2026Article
- The interaction between paracetamol and ethanol during the early development of zebrafish.Frontiers in pharmacology · 2026Article
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDue to its availability and perceived safety, paracetamol is recommended even during pregnancy and for neonates. It is used frequently alone or in combination with other drugs required for the treatment of various chronic conditions. The aim of this study was to investigate potential effects of drug interactions on paracetamol metabolism and its placental transfer and entry into the developing brain.
methodsSprague Dawley rats at postnatal day P4, pregnant embryonic day E19 dams, and non-pregnant adult females were administered paracetamol (15 mg/kg) either as monotherapy or in combination with one of seven other drugs: cimetidine, digoxin, fluvoxamine, lamotrigine, lithium, olanzapine, valproate. Concentrations of parent paracetamol and its metabolites (paracetamol-glucuronide, paracetamol-glutathione, and paracetamol-sulfate) in plasma, cerebrospinal fluid (CSF) and brain were measured by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) and their entry into the brain, CSF and transfer across the placenta were estimated.
resultsIn monotherapy, concentration of parent paracetamol in plasma, CSF, and brain remained similar and at all ages brain entry was unrestricted. In combination therapies, CSF entry of paracetamol increased following co-treatment with olanzapine. Placental transfer of parent paracetamol remained unchanged, however, transfer of paracetamol-sulfate increased with lamotrigine co-administration. Acutely administered paracetamol was more extensively metabolized in adults compared to younger ages resulting in increased concentration of its metabolites with age.
conclusionsDevelopmental changes in the apparent brain and CSF entry of paracetamol appear to be determined more by its metabolism, rather than by cellular control of its transfer across brain and placental barriers.
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