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

Biomedicine & Pharmacotherapy (Oct 2022)

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

Affiliations

Jung-Hung Chen: Institute of Traditional Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan
I-Hsin Lin: Institute of Traditional Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan
Chung-Kai Sun: Institute of Traditional Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan
Ling Yang: Institute of Traditional Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan
Thomas Y. Hsueh: Division of Urology, Department of Surgery, Taipei City Hospital Renai Branch, Taipei 106, Taiwan; Department of Urology, School of Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan
Chin-Tsung Ting: Division of Gastrointestinal Surgery, Department of Surgery, Renai Branch, Taipei City Hospital, Taipei 106, Taiwan; General Education Center, University of Taipei, Taipei 100, Taiwan
Tung-Hu Tsai: Institute of Traditional Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan; Graduate Institute of Acupuncture Science, China Medical University, Taichung 40402, Taiwan; Department of Education and Research, Taipei City Hospital, Taipei 106, Taiwan; Correspondence to: Institute of Traditional Medicine, College of Medicine, National Yang Ming Chiao Tung University, 155, Li-Nong Street Section 2, Taipei 112, Taiwan.

Journal volume & issue: Vol. 154
p. 113613

Abstract

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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.

Published in Biomedicine & Pharmacotherapy

ISSN: 0753-3322 (Print); 1950-6007 (Online)
Publisher: Elsevier
Country of publisher: France
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: https://www.journals.elsevier.com/biomedicine-and-pharmacotherapy

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