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Pharmacokinetics and Tissue Distribution of Rosuvastatin in a Rat Model of Preeclampsia
Version 1
: Received: 28 May 2024 / Approved: 29 May 2024 / Online: 29 May 2024 (11:56:56 CEST)
A peer-reviewed article of this Preprint also exists.
Dai, W.; Piquette-Miller, M. Altered Expression of BCRP Impacts Fetal Accumulation of Rosuvastatin in a Rat Model of Preeclampsia. Pharmaceutics 2024, 16, 884. Dai, W.; Piquette-Miller, M. Altered Expression of BCRP Impacts Fetal Accumulation of Rosuvastatin in a Rat Model of Preeclampsia. Pharmaceutics 2024, 16, 884.
Abstract
Expression of the breast cancer resistance protein (BCRP/ ABCG2) transporter is downregulated in placentas from women with preeclampsia (PE) and in an immunological rat model of PE, which closely resembles human PE. While many drugs are substrates of this important efflux transporter, the impact of BCRP downregulation on maternal and fetal drug exposure has not been investigated. Using the PE rat model, we performed a pharmacokinetic study with rosuvastatin (RSV), a BCRP substrate, to investigate this impact. PE was induced in rats during gestational days (GD) 13 to 16 with daily low-dose endotoxin. On GD18, RSV (3 mg/kg) was administrated intravenously, and rats were sacrificed at time intervals between 0.5-6 hours. Placental expression of Bcrp and Oatp2b1 significantly decreased in PE rats. A corresponding increase in RSV levels was seen in fetal tissues and amniotic fluid of the PE group (p<0.05), while maternal plasma concentrations remained unchanged. An increase in Bcrp expression and decreased RSV concentration, was seen in the livers of PE dams. This suggests that PE-mediated transporter dysregulation leads to significant changes in the maternal and fetal RSV disposition. Overall, our findings demonstrate that altered placental expression of transporters in PE can increase fetal accumulation of their substrates.
Keywords
breast cancer resistance protein; preeclampsia; pharmacokinetic; pregnancy; transporters
Subject
Medicine and Pharmacology, Pharmacology and Toxicology
Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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