The Role of PXR Genotype and Transporter Expression in the Placental Transport of Lopinavir in Mice
AbstractLopinavir (LPV), an antiretroviral protease inhibitor frequently prescribed in HIV-positive pregnancies, is a substrate of Abcb1 and Abcc2. As differences in placental expression of these transporters were seen in Pregnane X Receptor (PXR) −/− mice, we examined the impact of placental transporter expression and fetal PXR genotype on the fetal accumulation of LPV. PXR +/− dams bearing PXR +/+, PXR +/−, and PXR −/− fetuses were generated by mating PXR +/− female mice with PXR +/− males. On gestational day 17, dams were administered 10 mg/kg LPV (i.v.) and sacrificed 30 min post injection. Concentrations of LPV in maternal plasma and fetal tissue were measured by LC-MS/MS, and transporter expression was determined by quantitative RT-PCR. As compared to the PXR +/+ fetal units, placental expression of Abcb1a, Abcc2, and Abcg2 mRNA were two- to three-fold higher in PXR −/− fetuses (p < 0.05). Two-fold higher fetal:maternal LPV concentration ratios were also seen in the PXR +/+ as compared to the PXR −/− fetuses (p < 0.05), and this significantly correlated to the placental expression of Abcb1a (r = 0.495; p < 0.005). Individual differences in the expression of placental transporters due to genetic or environmental factors can impact fetal exposure to their substrates. View Full-Text
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Gahir, S.S.; Piquette-Miller, M. The Role of PXR Genotype and Transporter Expression in the Placental Transport of Lopinavir in Mice. Pharmaceutics 2017, 9, 49.
Gahir SS, Piquette-Miller M. The Role of PXR Genotype and Transporter Expression in the Placental Transport of Lopinavir in Mice. Pharmaceutics. 2017; 9(4):49.Chicago/Turabian Style
Gahir, Sarabjit S.; Piquette-Miller, Micheline. 2017. "The Role of PXR Genotype and Transporter Expression in the Placental Transport of Lopinavir in Mice." Pharmaceutics 9, no. 4: 49.
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