Transplacental transfer of acetaminophen in pregnant rats

Jung Hung Chen, I. Hsin Lin, Chung Kai Sun, Ling Yang, Thomas Y. Hsueh, Chin Tsung Ting, Tung Hu Tsai*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Acetaminophen is among the most widely used analgesics; however, the proportion and mechanism of transplacental transfer of unbound acetaminophen with actual pharmacological activity remain unknown. Our hypothesis is that acetaminophen gradually penetrates the blood-placenta barrier to reach the fetus. A multiple microdialysis coupled to liquid chromatography with photodiode array detection method was developed to monitor acetaminophen levels in the maternal blood, placenta, fetus, and amniotic fluid of a pregnant rat and investigate this hypothesis. The pharmacokinetic data indicates that acetaminophen exhibits a nonlinear behavior in the maternal blood within the dosage regimen of 100 and 300 mg/kg. In addition, acetaminophen penetrates the placenta, fetus, and amniotic fluid during treatment. The transplacental transfer ratio represented by the area under the concentration curve (AUC) ratio for the conceptus (the collective term for the fetus, placenta, and amniotic fluid) and maternal blood (AUCtissue/AUCblood) was approximately 11–23 % after acetaminophen (100 and 300 mg/kg) administration. However, the transporter of multidrug resistance-associated protein (MRP) inhibitor MK-571 did not significantly change the transplacental transfer ratio. This basic study provides constructive information for the clinical application of acetaminophen in pregnant women.

Original languageEnglish
Article number113613
JournalBiomedicine and Pharmacotherapy
StatePublished - Oct 2022


  • Acetaminophen
  • Microdialysis
  • Pharmacokinetics
  • Transplacental transfer


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