Etravirine inhibits ABCG2 drug transporter and affects transplacental passage of tenofovir disoproxil fumarate

Reznicek, Josef; Čečková, Martina; Tupova, Lenka; Štaud, František

doi:10.1016/j.placenta.2016.09.019

Cited by 13 publications

(7 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…P-gp and BCRP expression in the placenta could be regulated at the transcriptional, translational and post-translational levels [79,83,89,136]. Recent studies indicate that the roles of P-gp (likely BCRP as well) in determining fetal drug exposure depend on drugs administered even if the drugs are their substrates, a phenomenon that could be interpreted by the concept of fraction of drug transported [51,56,57,61,80,91,92,95,137,138]. In addition, since many transporters overlap in substrate specificity due to their promiscuous nature, transport of substrates by P-gp or BCRP in the placenta could be influenced by other transporters.…”

Section: Resultsmentioning

confidence: 99%

“…A dual human placental perfusion study showed that nicardipine, a BCRP inhibitor, partially blocked the transfer of glyburide across the whole placenta presumably by inhibition of BCRP [91]. A dually rat placenta perfusion study revealed that etravirine (antiviral) reduced trans-placental passage of tenofovir disoproxil fumarate (antiviral) likely through inhibition of Bcrp [92]. The role of BCRP as a bile acid transporter in the placenta has been characterized.…”

Section: P-gp and Bcrp In The Placentamentioning

confidence: 99%

See 1 more Smart Citation

An update on expression and function of P-gp/ABCB1 and BCRP/ABCG2 in the placenta and fetus

Han

Gao

Mao

2018

Expert Opinion on Drug Metabolism & Toxicology

View full text Add to dashboard Cite

P-glycoprotein (P-gp)/ABCB1 and breast cancer resistance protein (BCRP)/ABCG2 are highly expressed in the placenta and fetus throughout gestation and can modulate exposure and toxicity of drugs and xenobiotics to the vulnerable fetus during the sensitive times of growth and development. We aim to provide an update on current knowledge on placental and fetal expressions of the two transporters in different species, and to provide insight on interpreting transporter expression and fetal exposure relative to the concept of fraction of drug transported. Areas covered: Comprehensive literature review through PubMed (primarily from July 2010 to February 2018) on P-gp and BCRP expression and function in the placenta and fetus of primarily human, mouse, rat, and guinea pig. Expert opinion: While there are many commonalities in the expression and function of P-gp and BCRP in the placenta and fetal tissues across species, there are distinct differences in expression levels and temporal changes. Further studies are needed to quantify protein abundance of these transporters and functionally assess their activities at various gestational stages. Combining the knowledge of interspecies differences and the concept of fraction of drug transported, we may better predict the magnitude of impact these transporters have on fetal drug exposure.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: P-gp and Bcrp In The Placentamentioning

confidence: 99%

An update on expression and function of P-gp/ABCB1 and BCRP/ABCG2 in the placenta and fetus

Han

Gao

Mao

2018

Expert Opinion on Drug Metabolism & Toxicology

View full text Add to dashboard Cite

show abstract

“…Raltegravir is transported by P‐gp/ABCB1 but also by BCRP/ABCG2, which are both highly expressed in epididymis and induced by etravirine . Etravirine, after a single dose, was also reported to be a potent inhibitor of BCRP/ABCG2 and not an inhibitor of P‐gp/ABCB1 .…”

Section: Discussionmentioning

confidence: 99%

Lack of a Clinically Significant Pharmacokinetic Interaction between Etravirine and Raltegravir Using an Original Approach Based on Drug Metabolism, Protein Binding, and Penetration in Seminal Fluid: A Pharmacokinetic Substudy of the ANRS‐163 ETRAL Study

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Transplacental transport to the fetus is susceptible to DDIs. Research showed for example that ETR inhibits placental ABC transporter BCRP (ABCG2) in vitro, and ritonavir inhibits several placental ABC transporters at physiological concentrations [87,88]. Etravirine and ritonavir can, therefore, increase the fetal exposure of co-administered PIs or lamivudine, which are known substrates of the placental ABC transporters [88].…”

Section: Etravirine and Tenofovir Disoproxil Fumarate: An Additional mentioning

confidence: 99%

Drug–Drug Interactions with Antiretroviral Drugs in Pregnant Women Living with HIV: Are They Different from Non-Pregnant Individuals?

et al. 2020

View full text Add to dashboard Cite

Background and Objective Although the separate effects of drug-drug interactions and pregnancy on antiretroviral drug pharmacokinetics have been widely studied and described, their combined effect is largely unknown. Physiological changes during pregnancy may change the extent or clinical relevance of a drug-drug interaction in a pregnant woman. This review aims to provide a detailed overview of the mechanisms, magnitude, and clinical significance of antiretroviral drug-drug interactions in pregnant women. Methods We performed a literature search and selected studies that compared the magnitude of drug-drug interactions with antiretroviral drugs in pregnant vs non-pregnant women. Results Forty-eight papers examining drug-drug interactions during pregnancy were selected, of which the majority focused on pharmacokinetic boosting. Other selected studies examined the drug-drug interactions between efavirenz and lumefantrine, efavirenz and tuberculosis drugs, etravirine and tenofovir disoproxil fumarate, atazanavir and tenofovir disoproxil, and mefloquine and nevirapine in pregnant compared to non-pregnant women. The clinical significance of antiretroviral drug-drug interactions changed during pregnancy from a minimal effect to a contra-indication. In almost all cases, the clinical significance of a drug-drug interaction was more relevant in pregnant women, owing to the combined effects of pregnancyinduced physiological changes and drug-drug interactions leading to a lower absolute drug exposure. Conclusions Multiple studies show that the clinical relevance of a drug-drug interaction can change during pregnancy. Unfortunately, many potential interactions have not been studied in pregnancy, which may place pregnant women living with human immunodeficiency virus and their newborns at risk.

show abstract

Etravirine inhibits ABCG2 drug transporter and affects transplacental passage of tenofovir disoproxil fumarate

Cited by 13 publications

References 22 publications

An update on expression and function of P-gp/ABCB1 and BCRP/ABCG2 in the placenta and fetus

An update on expression and function of P-gp/ABCB1 and BCRP/ABCG2 in the placenta and fetus

Lack of a Clinically Significant Pharmacokinetic Interaction between Etravirine and Raltegravir Using an Original Approach Based on Drug Metabolism, Protein Binding, and Penetration in Seminal Fluid: A Pharmacokinetic Substudy of the ANRS‐163 ETRAL Study

Drug–Drug Interactions with Antiretroviral Drugs in Pregnant Women Living with HIV: Are They Different from Non-Pregnant Individuals?

Contact Info

Product

Resources

About