Placental transfer of xenobiotics in pregnancy physiologically-based pharmacokinetic models: Structure and data

Codaccioni, Marc; Brochot, Céline

doi:10.1016/j.comtox.2019.100111

Cited by 19 publications

(22 citation statements)

References 150 publications

(194 reference statements)

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“…During the last trimester, the thickness of the barrier significantly decreases as the cytotrophoblast disappears and fetal vessels get closer to the villus surface. The exchange zones of the barrier consist of only membranes of syncytiotropholast and adjacent capillaries walls (Chatuphonprasert et al, 2018;Codaccioni et al, 2019;Schatten and Constantinescu, 2007). Although it is unclear how HIV-1 viruses cross the placenta, the risk of transmission is increased during the third trimester when the placental barrier becomes thinner.…”

Section: Discussionmentioning

confidence: 99%

Different evolutionary pathways of HIV-1 between fetus and mother perinatal transmission pairs indicate unique immune selection pressure in fetuses

Marichannegowda

Mengual

Kumar

et al. 2020

Preprint

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SummaryStudy of evolution and selection pressure on HIV-1 in fetuses will lead to a better understanding of the role of immune responses in shaping virus evolution and vertical transmission. Detailed genetic analyses of HIV-1 env gene from 12 in utero transmission pairs show that most infections (67%) occur within two months from childbirth. In addition, env sequences from long-term infected fetuses were highly divergent and formed separate phylogenetic lineages from their cognate maternal viruses. Host selection sites unique to infant viruses were identified in regions frequently targeted by broadly neutralizing antibodies and T cell immune responses. The identification of unique selection sites in the env gene of fetal viruses indicates that the immune system in fetuses is capable of exerting selection pressure on viral evolution. Studying selection and evolution of HIV-1 or other viruses in fetuses can be an alternative approach to investigate adaptive immunity in fetuses.

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Section: Discussionmentioning

confidence: 99%

Different evolutionary pathways of HIV-1 between fetus and mother perinatal transmission pairs indicate unique immune selection pressure in fetuses

Marichannegowda

Mengual

Kumar

et al. 2020

Preprint

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“…Early exposure to these toxins, which have overlapping neurotoxic and endocrine-disrupting properties, can therefore lead to neurodevelopmental complications, with some coining the term neural-disrupting chemicals [107]. Experimental studies in humans and rodents have shown that most of these toxins cross both placental and blood-brain barriers [108,109], enabling their neurodevelopmental toxicity. The endocrine effects of these toxins may also contribute to the male bias observed in ASD diagnoses.…”

Section: Air Pollutants Heavy Metals Pops and Non-pops And Pesticidesmentioning

confidence: 99%

Exposure to Xenobiotics and Gene-Environment Interactions in Autism Spectrum Disorder: A Systematic Review

Santos¹,

Rasga²,

Vicente³

2021

Autism Spectrum Disorder - Profile, Heterogeneity, Neurobiology and Intervention

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Heritability estimates indicate that genetic susceptibility does not fully explain Autism Spectrum Disorder (ASD) risk variance, and that environmental factors may play a role in this disease. To explore the impact of the environment in ASD etiology, we performed a systematic review of the literature on xenobiotics implicated in the disease, and their interactions with gene variants. We compiled 72 studies reporting associations between ASD and xenobiotic exposure, including air pollutants, persistent and non-persistent organic pollutants, heavy metals, pesticides, pharmaceutical drugs and nutrients. Additionally, 9 studies reported that interactions between some of these chemicals (eg. NO2, particulate matter, manganese, folic acid and vitamin D) and genetic risk factors (eg. variants in the CYP2R1, GSTM1, GSTP1, MET, MTHFR and VDR genes) modulate ASD risk. The chemicals highlighted in this review induce neuropathological mechanisms previously implicated in ASD, including oxidative stress and hypoxia, dysregulation of signaling pathways and endocrine disruption. Exposure to xenobiotics may be harmful during critical windows of neurodevelopment, particularly for individuals with variants in genes involved in xenobiotic metabolization or in widespread signaling pathways. We emphasize the importance of leveraging multilevel data collections and integrative approaches grounded on artificial intelligence to address gene–environment interactions and understand ASD etiology, towards prevention and treatment strategies.

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“…Data from either in silico models, in vitro cell systems, ex vivo placental perfusion systems, or animal and human data are required to estimate placental transfer, which is further incorporated into the p-PBPK model. 66 Verification of the fetal exposure in these models is possible only when umbilical cord concentrations are available at term. Further refinements in these models as we learn more about pregnancy-mediated changes in drug absorption, distribution, transport, metabolism, excretion, and placental transport will provide more confidence in such models to predict drug exposure and needed drug-dosing changes in pregnancy.…”

Section: Application Of Pbpk Modeling To Predict Exposure Of Renally mentioning

confidence: 99%

“…These include inability to predict fetal exposure by itself (when a fetoplacental compartment is used) and to verify fetal exposure over the dosing interval. Data from either in silico models, in vitro cell systems, ex vivo placental perfusion systems, or animal and human data are required to estimate placental transfer, which is further incorporated into the p‐PBPK model 66 . Verification of the fetal exposure in these models is possible only when umbilical cord concentrations are available at term.…”

Section: Model‐based Approachesmentioning

confidence: 99%

Model‐Informed Dose Optimization in Pregnancy

Chaphekar

Caritis

Venkataramanan

2020

The Journal of Clinical Pharma

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Pregnancy is associated with several physiological changes that can alter the pharmacokinetics (PK) and pharmacodynamics of drugs. These may require dosing changes in pregnant women to achieve drug exposures comparable to the nonpregnant population. There is, however, limited information available on the PK and pharmacodynamics of drugs used during pregnancy. Practical difficulties in performing PK studies and potential liability issues are often the reasons for the availability of limited information. Over the past several years, there has been a rapid development in the application of various modeling strategies such as population PK and physiologically based PK modeling to provide guidance on drug dosing in this special patient population. Population PK models rely on measured PK data, whereas physiologically based PK models integrate physiological, preclinical, and clinical data to quantify changes in PK of drugs in various patient populations. These modeling strategies offer a promising approach to identify the drugs with PK changes during pregnancy and guide dose adjustment in pregnant women. This review focuses on PBPK modeling to guide drug therpay in pregnancy.

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Placental transfer of xenobiotics in pregnancy physiologically-based pharmacokinetic models: Structure and data

Cited by 19 publications

References 150 publications

Different evolutionary pathways of HIV-1 between fetus and mother perinatal transmission pairs indicate unique immune selection pressure in fetuses

Different evolutionary pathways of HIV-1 between fetus and mother perinatal transmission pairs indicate unique immune selection pressure in fetuses

Exposure to Xenobiotics and Gene-Environment Interactions in Autism Spectrum Disorder: A Systematic Review

Model‐Informed Dose Optimization in Pregnancy

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