Increased Expression of MDR1 mRNAs and P-glycoprotein in Placentas from HIV-1 Infected Women

Camus, M.; Deloménie, Claudine; Didier, Nathalie; Faye, Albert; Gil, Sophie; Dauge, Marie-Christine; Mabondzo, Aloı̈se; Farinotti, Robert

doi:10.1016/j.placenta.2005.08.001

Cited by 34 publications

(30 citation statements)

References 56 publications

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“…1, A and B). Other laboratories have shown that MDR1 expression is not dependent on the region of the sample or on cesarean versus vaginal delivery (Camus et al, 2006;Sun et al, 2006). MRP1, MRP2, and MDR3 were present in all samples, but their expression was variable and did not appear to be dramatically affected by pregnancy condition (Fig.…”

Section: Resultsmentioning

confidence: 73%

ATP-Binding Cassette Transporter Expression in Human Placenta as a Function of Pregnancy Condition

Mason

Buhimschi²,

Buhimschi³

et al. 2011

Drug Metab Dispos

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ABSTRACT:Fetal drug exposure is determined by the type and concentration of placental transporters, and their regulation is central to the development of new treatments and delivery strategies for pregnant women and their fetuses. We tested the expression of several clinically important transporters in the human placenta associated with various pregnancy conditions (i.e., labor, preeclampsia, and preterm labor-inflammation). Placentas were obtained from five groups of women at the time of primary cesarean section: 1) term no labor; 2) term labor; 3) preterm no labor (delivered for severe preeclampsia); 4) preterm labor without inflammation (PTLNI); and 5) preterm labor with inflammation (PTLI). Samples were analyzed by Western blot and immunohistochemistry to identify changes in protein expression. Relative mRNA expression was determined by quantitative real-time polymerase chain reaction. A functional genomic approach was used to identify placental gene expression and elucidate molecular events that underlie the given condition. Placental expression of ATP-binding cassette transporters from women in labor and women with preeclampsia was unaltered. Multidrug resistance protein 1 (MDR1) and breast cancer resistance protein (BCRP) and mRNA expression increased in placentas of women with preterm labor with inflammation. Molecular pathways of genes up-regulated in PTLI samples included cytokinecytokine receptor interactions and inflammatory response compared with those in the PTLNI group. The mRNA expression of MDR1 and BCRP was correlated with that of interleukin-8, which also increased significantly in PTLI samples. These data suggest that the transfer of drugs across the placenta may be altered in preterm pregnancy conditions associated with inflammation through changes in MDR1 and BCRP.

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Section: Resultsmentioning

confidence: 73%

ATP-Binding Cassette Transporter Expression in Human Placenta as a Function of Pregnancy Condition

Mason

Buhimschi²,

Buhimschi³

et al. 2011

Drug Metab Dispos

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“…As drug-drug interactions on ABC transporters may substantially affect the fate of drugs in organism, our findings should be taken into account when TDF is co-administered with compounds whose membrane transport is mediated by ABCB1 and/ or ABCG2 such as antiretrovirals [41] or other drugs administered in pregnancy [8]. Differences in ABCB1 expression between HIV-infected and noninfected women [42] as well as genetic polymorphisms leading to altered expression and function of the protein in the placenta [43] should also be considered when substrate drugs are prescribed.…”

Section: Discussionmentioning

confidence: 91%

Interactions of tenofovir and tenofovir disoproxil fumarate with drug efflux transporters ABCB1, ABCG2, and ABCC2; role in transport across the placenta

Neumanova

Červený²,

Čečková³

et al. 2014

Aids

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“…One study suggested a significantly higher, 3.3-fold (p < 0.0009) mean increase in the expression of the MDR1 gene in the placentas of HIV-infected versus uninfected women [105]. This gene encodes P-glycoprotein, which can result in efflux transport of many protease inhibitors [105].…”

Section: Resultsmentioning

confidence: 99%

“…This gene encodes P-glycoprotein, which can result in efflux transport of many protease inhibitors [105]. The increased expression did not appear to be confounded by protease inhibitor administration to the HIV-infected group, as a similar extent of increased expression was observed whether the women were treated with zidovudine alone or in combination with nelfinavir and lamivudine [105]. This finding may account in part for difficulty in transplacental transport of protease inhibitors in HIV-infected women.…”

Section: Resultsmentioning

confidence: 99%

Protecting the Fetus Against HIV Infection: A Systematic Review of Placental Transfer of Antiretrovirals

McCormack

Best

2014

Clin Pharmacokinet

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Background Maternal-fetal transfer of antiretroviral drugs contributes to prevention of vertical transmission of HIV. Objective This systematic review discusses published studies containing data pertaining to the pharmacokinetics of placental transfer in humans, including paired cord and maternal plasma samples collected at the time of delivery as well as ex vivo placental perfusion models. Methods Articles pertaining to placental transfer of antiretrovirals were identified from PubMed, from references of included articles, and from U.S. Department of Health and Human Services Panel on Treatment of HIV-infected Pregnant Women and Prevention of Perinatal Transmission guidelines. Articles from non-human animal models or that had no original maternal-fetal transfer data were excluded. PRISMA guidelines were followed. Results A total of 103 published studies were identified. Data across studies appeared relatively consistent for the nucleoside reverse transcriptase inhibitors (NRTIs) and the non-nucleotide reverse transcriptase inhibitors (NNRTIs), with cord to maternal ratios approaching 1 for many of these agents. The protease inhibitors atazanavir and lopinavir exhibited consistent maternal-to-fetal transfer across studies, although the transfer may be influenced by variations in drug-binding proteins. The protease inhibitors indinavir, nelfinavir, and saquinavir exhibited unreliable placental transport, with cord blood concentrations that were frequently undetectable. Limited data, primarily from case reports, indicate that darunavir and raltegravir provide detectable placental transfer. Conclusion These findings appear consistent with current guidelines of using two NRTIs plus an NNRTI, atazanavir/ritonavir, or lopinavir/ritonavir to maximize placental transfer as well as to optimally suppress maternal viral load. Darunavir/ritonavir and raltegravir may reasonably serve as second-line agents.

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Increased Expression of MDR1 mRNAs and P-glycoprotein in Placentas from HIV-1 Infected Women

Cited by 34 publications

References 56 publications

ATP-Binding Cassette Transporter Expression in Human Placenta as a Function of Pregnancy Condition

ATP-Binding Cassette Transporter Expression in Human Placenta as a Function of Pregnancy Condition

Interactions of tenofovir and tenofovir disoproxil fumarate with drug efflux transporters ABCB1, ABCG2, and ABCC2; role in transport across the placenta

Protecting the Fetus Against HIV Infection: A Systematic Review of Placental Transfer of Antiretrovirals

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