The Human Placental Perfusion Model: A Systematic Review and Development of a Model to Predict In Vivo Transfer of Therapeutic Drugs
Abstract
Dual perfusion of a single placental lobule is the only experimental model to study human placental transfer of substances in organized placental tissue. To date, there has not been any attempt at a systematic evaluation of this model. The aim of this study was to systematically evaluate the perfusion model in predicting placental drug transfer and to develop a pharmacokinetic model to account for nonplacental pharmacokinetic parameters in the perfusion results. In general, the fetal-to-maternal drug concentration ratios matched well between placental perfusion experiments and in vivo samples taken at the time of delivery of the infant. After modeling for differences in maternal and fetal/neonatal protein binding and blood pH, the perfusion results were able to accurately predict in vivo transfer at steady state (R² = 0.85, P < 0.0001). Placental perfusion experiments can be used to predict placental drug transfer when adjusting for extra parameters and can be useful for assessing drug therapy risks and benefits in pregnancy.
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Dual-perfusion of the delivered placenta has validated transfer for approximately 50 drugs.
“Comparison of the data with maternal-fetal in vivo measurements has validated transfer for approximately 50 drugs (266).”
From Placental Origins of Chronic Disease (2016) · cites this paper as [266]
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Gold nanoparticle distribution in advanced in vitro and ex vivo human placental barrier models
Aengenheister, L., Dietrich, D., Sadeghpour, A., Manser, P., Diener, L., Wichser, A., Kärst, U., Wick, P., & Buerki‐Thurnherr, T. (2018) · Journal of Nanobiotechnology · doi:10.1186/s12951-018-0406-6 · Cited by 71 · see citing works
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Antiseizure medication use during pregnancy and risk of ASD and ADHD in children
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Understanding the Chemical Exposome During Fetal Development and Early Childhood: A Review
Krausová, M., Braun, D., Buerki-Thurnherr, T., Gundacker, C., Schernhammer, E., Wisgrill, L., & Warth, B. (2023) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-051922-113350 · Cited by 61 · see citing works
Rivaroxaban transfer across the dually perfused isolated human placental cotyledon
Bapat, P., Pinto, L., Lubetsky, A., Berger, H. M., & Koren, G. (2015) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2015.06.065 · Cited by 60 · see citing works
“protein binding and liver metabolism), the placenta perfusion is the only experimental model that can be used to study human placental transfer of substances in organized placental tissue and may be able more reliably to predict fetal exposure compared with other experimental methods.(24) Although animal studies can b…”
BackgroundResultSelf-citationKnocking at the door of the unborn child: engineered nanoparticles at the human placental barrier
Buerki‐Thurnherr, T., von Mandach, U., & Wick, P. (2012) · Swiss Medical Weekly · doi:10.4414/smw.2012.13559 · Cited by 59 · see citing works
Freriksen, J. J. M., van Seyen, M., Judd, A., Gibb, D. M., Collins, I. J., Greupink, R., Rüssel, F. G. M., Drenth, J. P. H., Colbers, A. P. H., & Burger, D. M. (2019) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.15476 · Cited by 58 · see citing works
Grafmüller, S., Manser, P., Krug, H. F., Wick, P., & von Mandach, U. (2013) · Journal of Visualized Experiments · doi:10.3791/50401 · Cited by 57 · see citing works
Elzinga, F. A., Khalili, B., Touw, D. J., Prins, J. R., Olinga, P., Leuvenink, H. G. D., van Goor, H., Gordijn, S. J., Nagelkerke, A., & Mian, P. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12134315 · Cited by 56 · see citing works
“Furthermore, the placental perfusion model is not suitable to study placental transfer during the most vulnerable period for the embryonic organogenesis: the first or early second trimester of pregnancy [12,13].”
BackgroundResearch on nanoparticles in human perfused placenta: State of the art and perspectives
Aengenheister, L., Fávaro, R. R., Prieto, D. M. M., Furer, L. A., Gruber, M., Wadsack, C., Markert, U. R., & Buerki‐Thurnherr, T. (2020) · Placenta · doi:10.1016/j.placenta.2020.12.014 · Cited by 57 · see citing works
“For these, good correlation between transfer rates from perfusion studies with physiological data has been obtained [63].”
BackgroundShojaei, S., Ali, M. S., Suresh, M., Upreti, T., Mogourian, V., Helewa, M. E., & Labouta, H. I. (2021) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2021.166131 · Cited by 55 · see citing works
Placental Transfer of Fc‐Containing Biopharmaceuticals across Species, an Industry Survey Analysis
Bowman, C., Breslin, W. J., Connor, A. V., Martin, P. L., Moffat, G. J., Sivaraman, L., Tornesi, M. B., & Chivers, S. (2013) · Birth Defects Research Part B Developmental and Reproductive Toxicology · doi:10.1002/bdrb.21089 · Cited by 54 · see citing works
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“[6], resulted in a predicted fupF of 0.”
BackgroundInfluentialMaternal Immunization: Nature Meets Nurture
Saso, A., & Kampmann, B. (2020) · Frontiers in Microbiology · doi:10.3389/fmicb.2020.01499 · Cited by 53 · see citing works
Use of thiopurines in inflammatory bowel disease: Safety issues
Konidari, A., & El‐Matary, W. (2014) · World Journal of Gastrointestinal Pharmacology and Therapeutics · doi:10.4292/wjgpt.v5.i2.63 · Cited by 51 · see citing works
Examining the transplacental passage of apixaban using the dually perfused human placenta
Bapat, P., Pinto, L., Lubetsky, A., Aleksa, K., Berger, H. M., Koren, G., & Ito, S. (2016) · Journal of Thrombosis and Haemostasis · doi:10.1111/jth.13353 · Cited by 50 · see citing works
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In vitro simulation of placental transport: Part I. Biological model of the placental barrier
Levkovitz, R., Zaretsky, U., Gordon, Z., Jaffa, A. J., & Elad, D. (2013) · Placenta · doi:10.1016/j.placenta.2013.03.014 · Cited by 47 · see citing works
Goeden, N., & Bonnin, A. (2012) · Nature Protocols · doi:10.1038/nprot.2012.144 · Cited by 44 · see citing works
Muoth, C., Großgarten, M., Kärst, U., Ruiz, J., Astruc, D., Moya, S. E., Diener, L., Grieder, K., Wichser, A., Jochum, W., et al. (2017) · Nanomedicine · doi:10.2217/nnm-2017-0428 · Cited by 46 · see citing works
Mose, T., Mathiesen, L., Karttunen, V., Nielsen, J. K. S., Sieppi, E., Kummu, M., Mørck, T. A., Myöhänen, K., Partanen, H., Vähäkangas, K., et al. (2012) · Placenta · doi:10.1016/j.placenta.2012.02.004 · Cited by 45 · see citing works
Current and future antenatal management of isolated congenital diaphragmatic hernia
Russo, F. M., Coppi, P. D., Allegaert, K., Toelen, J., der Veeken, L. V., Attilakos, G., Eastwood, M. P., David, A. L., & Deprest, J. A. (2017) · Seminars in Fetal and Neonatal Medicine · doi:10.1016/j.siny.2017.11.002 · Cited by 45 · see citing works
“As a next step to clinical translation, we evaluated transfer of sildenafil through the human placenta, by using an ex-vivo placenta perfusion model [70].”
MethodComparative transplacental transfer of taxanes using the human perfused cotyledon placental model
Berveiller, P., Vinot, C., Mir, O., Broutin, S., Deroussent, A., Seck, A., Camps, S., Paci, A., Gil, S., & Tréluyer, J. (2012) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2012.10.007 · Cited by 43 · see citing works
Methodological Approaches to Evaluate Fetal Drug Exposure
Bouazza, N., Foissac, F., Hirt, D., Urien, S., Benaboud, S., Lui, G., & Tréluyer, J. (2019) · Current Pharmaceutical Design · doi:10.2174/1381612825666190319102812 · Cited by 42 · see citing works
Freriksen, J. J. M., Schalkwijk, S. J., Colbers, A. P. H., Abduljalil, K., Rüssel, F. G. M., Burger, D. M., & Greupink, R. (2019) · Clinical Pharmacology & Therapeutics · doi:10.1002/cpt.1748 · Cited by 42 · see citing works
“It has been shown that ex vivo placenta perfusion is a valid method to study placental transfer of compounds and is predictive of placental transfer in vivo.(17,18) We previously demonstrated that mechanistic data derived from ex vivo placental perfusion experiments can be used for parameterization of the fetal-placen…”
BackgroundPlacental effects and transfer of sildenafil in healthy and preeclamptic conditions
Hitzerd, E., Broekhuizen, M., Colafella, K. M. M., Glišić, M., VRIES, R. D., Koch, B. C. P., de Raaf, M. A., Merkus, D., Schoenmakers, S., Reiss, I. K. M., et al. (2019) · EBioMedicine · doi:10.1016/j.ebiom.2019.06.007 · Cited by 41 · see citing works
“Ex vivo cotyledon perfusion is a safe method to predict placental transfer of drugs in vivo, avoiding foetal exposure [30].”
BackgroundMethodInfluentialPaulzen, M., Goecke, T. W., Stickeler, E., Gründer, G., & Schoretsanitis, G. (2017) · Journal of Affective Disorders · doi:10.1016/j.jad.2017.01.019 · Cited by 40 · see citing works
Schoretsanitis, G., Westin, A., Deligiannidis, K., Spigset, O., & Paulzen, M. (2020) · Therapeutic Drug Monitoring · doi:10.1097/ftd.0000000000000692 · Cited by 31 · see citing works
Vinot, C., Gavard, L., Tréluyer, J., Manceau, S., Courbon, E., Scherrmann, J., Declèves, X., Duro, D., Peytavin, G., Mandelbrot, L., et al. (2013) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01821-12 · Cited by 38 · see citing works
“In the present study, we used the gold standard ex vivo human placental cotyledon perfusion model to evaluate the in vivo placental transfer of maraviroc by reproducing the conditions of the last trimester of pregnancy (37).”
MethodPlacental Villous Explant Culture 2.0: Flow Culture Allows Studies Closer to the In Vivo Situation
Kupper, N., Pritz, E., Siwetz, M., Guettler, J., & Huppertz, B. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22147464 · Cited by 38 · see citing works
“Although various advantages of this method are known, it is not suitable for experiments with first trimester placentas, and a complete intact organ, including intact blood vessels, is required for the perfusion of the fetal and the maternal side [11,23].”
MethodSchoretsanitis, G., Westin, A. A., Stingl, J., Deligiannidis, K. M., Paulzen, M., & Spigset, O. (2021) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2020.110228 · Cited by 37 · see citing works
“, 2015), but the physicochemical properties of the drugs might nevertheless be of importance (Hutson et al., 2011).”
BackgroundSchalkwijk, S. J., Greupink, R., Colbers, A. P. H., Wouterse, A. C., Verweij, V. G. M., van Drongelen, J., Teulen, M., van den Oetelaar, D., Burger, D. M., & Rüssel, F. G. M. (2015) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkv358 · Cited by 37 · see citing works
Cocaine and its metabolites in the placenta: A systematic review of the literature
Giovanni, N. D., & Marchetti, D. (2011) · Reproductive Toxicology · doi:10.1016/j.reprotox.2011.10.012 · Cited by 36 · see citing works
Graf, K., Murrieta-Coxca, J. M., Vogt, T., Besser, S., Geilen, D., Kaden, T., Bothe, A.-K., Prieto, D. M. M., Amiri, B., Schaller, S., et al. (2025) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1528748 · Cited by 35 · see citing works
Gély, C. A., Lacroix, M. Z., Morin, M., Vayssière, C., Gayrard, V., & Picard‐Hagen, N. (2021) · Chemosphere · doi:10.1016/j.chemosphere.2021.130213 · Cited by 32 · see citing works
Manceau, S., Giraud, C., Declèves, X., Scherrmann, J., Artiguebieille, F., Goffinet, F., Chappuy, H., Vinot, C., & Tréluyer, J. (2012) · Placenta · doi:10.1016/j.placenta.2012.07.016 · Cited by 33 · see citing works
Doppler evaluation of normal and abnormal placenta
Hernandez‐Andrade, E. A., Huntley, E. S., Bartal, M. F., Soto‐Torres, E. E., Tirosh, D., Jaiman, S., & Johnson, A. (2021) · Ultrasound in Obstetrics and Gynecology · doi:10.1002/uog.24816 · Cited by 32 · see citing works
Valéro, L., Alhareth, K., Gil, S., Simasotchi, C., Roques, C., Scherman, D., Mignet, N., Fournier, T., & Andrieux, K. (2017) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2017.07.076 · Cited by 32 · see citing works
Nanomedicine as a potential approach to empower the new strategies for the treatment of preeclampsia
Valéro, L., Alhareth, K., Gil, S., Lecarpentier, É., Tsatsaris, V., Mignet, N., Fournier, T., & Andrieux, K. (2018) · Drug Discovery Today · doi:10.1016/j.drudis.2018.01.048 · Cited by 32 · see citing works
Çalış, P. T., Vojtech, L. N., Hladik, F., & Gravett, M. G. (2021) · The Journal of Maternal-Fetal & Neonatal Medicine · doi:10.1080/14767058.2021.2005565 · Cited by 30 · see citing works
“With adjustments for protein binding and ion transfer results from modeling perfusion studies can accurately predict in vivo transfer of drugs at steady state [39].”
BackgroundBajoria, R., Sooranna, S. R., & Chatterjee, R. (2013) · Placenta · doi:10.1016/j.placenta.2013.10.005 · Cited by 29 · see citing works
“In general, the fetal-to-maternal drug concentration ratios matched well between placental perfusion experiments and in vivo samples taken at the time of delivery of the infant [31,32].”
BackgroundUpdate in Fetal Anesthesia for the Ex Utero Intrapartum Treatment (EXIT) Procedure
Ngamprasertwong, P., Vinks, A. A. T. M. M., & Boat, A. C. (2012) · International Anesthesiology Clinics · doi:10.1097/aia.0b013e31826df966 · Cited by 29 · see citing works
“Both in vitro and in vivo models have been used to study placental drug uptake and transfer and improve our understanding of PK and PD in the fetus.(45) In the past, PK studies in pregnancy were limited because of inability to obtain fetal blood or to draw multiple fetal blood samples.”
BackgroundEliesen, G. A. M., van Drongelen, J., van Hove, H., Kooijman, N. I., van den Broek, P., de Vries, A., Roeleveld, N., Rüssel, F. G. M., & Greupink, R. (2020) · Clinical Pharmacology & Therapeutics · doi:10.1002/cpt.1827 · Cited by 28 · see citing works
“For small molecule drugs, ex vivo placental transfer correlates well with in vivo cord-to-maternal ratios.(26) For antibody-based biologicals, however, results are more difficult to interpret, as placental transfer of IgG’s is slow compared with small molecules and only minimal transfer is expected to occur after 6 ho…”
BackgroundCriteria and challenges of the human placental perfusion – Data from a large series of perfusions.
Karttunen, V., Sahlman, H., Repo, J., Woo, C., Myöhänen, K., Myllynen, P., & Vähäkangas, K. (2015) · Toxicology in Vitro · doi:10.1016/j.tiv.2015.06.001 · Cited by 25 · see citing works
“However, antipyrine has been the most commonly used reference compound (for a review see e.g. Hutson et al., 2011) because of its properties such as low molecular weight and low protein binding without being metabolized by human placenta (Challier et al., 1983; Schneider et al., 1972).”
BackgroundComprehensive Measurements of Intrauterine and Postnatal Exposure to Lamotrigine
Paulzen, M., Stingl, J., Augustin, M., Saßmannshausen, H., Franz, C., Gründer, G., & Schoretsanitis, G. (2018) · Clinical Pharmacokinetics · doi:10.1007/s40262-018-0713-y · Cited by 27 · see citing works
Sildenafil for Antenatal Treatment of Congenital Diaphragmatic Hernia: From Bench to Bedside
Russo, F. M., Bie, F. R. D., Hodges, R. J., Flake, A. W., & Deprest, J. A. (2019) · Current Pharmaceutical Design · doi:10.2174/1381612825666190320151856 · Cited by 27 · see citing works
Heart rate changes mediate the embryotoxic effect of antiarrhythmic drugs in the chick embryo
Kočková, R., Svatunkova, J., Novotný, J., Hejnová, L., Ostadal, B., & Sedmera, D. (2013) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00679.2012 · Cited by 27 · see citing works
“The human placental model was developed as an experimental model to test transplacental perfusion of different drugs (12).”
MethodThe Placenta in Toxicology. Part IV
Göhner, C., Svensson‐Arvelund, J., Pfarrer, C. D., Häeger, J.-D., Faas, M. M., Ernerudh, J., Cline, J. M., Dixon, D., Buse, E., & Markert, U. R. (2013) · Toxicologic Pathology · doi:10.1177/0192623313482206 · Cited by 27 · see citing works
“A systematic evaluation of published results from the placenta perfusion model demonstrated that the maternal-to-fetal drug concentration ratios matched well between placental perfusion experiments and in vivo samples taken at the time of delivery of the infant (Hutson et al. 2011).”
Paulzen, M., Goecke, T. W., Stingl, J., Janssen, G., Stickeler, E., Gründer, G., & Schoretsanitis, G. (2017) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2017.06.030 · Cited by 27 · see citing works
Sildenafil crosses the placenta at therapeutic levels in a dually perfused human cotyledon model
Russo, F. M., Conings, S., Allegaert, K., Mieghem, T. V., Toelen, J., Calsteren, K. V., Annaert, P., & Deprest, J. A. (2018) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2018.08.041 · Cited by 27 · see citing works
Scabies-infested pregnant women: A critical therapeutic challenge
Weill, A., Bernigaud, C., Mokni, M., Gil, S., Éléfant, É., & Chosidow, O. (2021) · PLoS neglected tropical diseases · doi:10.1371/journal.pntd.0008929 · Cited by 26 · see citing works
“, HIV protease inhibitors or taxanes used in breast cancers), with good correlation between in vivo data and perfusion model [18].”
The transfer of 6-mercaptopurine in the dually perfused human placenta
Hutson, J. R., Lubetsky, A., Walfisch, A., Ballios, B. G., García‐Bournissen, F., & Koren, G. (2011) · Reproductive Toxicology · doi:10.1016/j.reprotox.2011.08.008 · Cited by 26 · see citing works
Self-citationCodaccioni, M., Bois, F. Y., & Brochot, C. (2019) · Computational Toxicology · doi:10.1016/j.comtox.2019.100111 · Cited by 24 · see citing works
Paulzen, M., Schoretsanitis, G., Gründer, G., Franz, C., Stingl, J., & Augustin, M. (2020) · Journal of Affective Disorders · doi:10.1016/j.jad.2020.02.010 · Cited by 25 · see citing works
Human placenta as an ex vivo vascular model for neurointerventional research
Kwok, J. C. K., Huang, W., Leung, W., Chan, S., Chan, K., Leung, K., Chu, A. C. H., & Lam, A. K. N. (2013) · Journal of NeuroInterventional Surgery · doi:10.1136/neurintsurg-2013-010813 · Cited by 25 · see citing works
Pencolé, L., Lê, M., Bouchet-Crivat, F., Duro, D., Peytavin, G., & Mandelbrot, L. (2020) · AIDS · doi:10.1097/qad.0000000000002637 · Cited by 25 · see citing works
“A literature review [45] showed that the ex-vivo results were predictive of the in-vivo situation when the cotyledon perfusion was performed at the same gestational age and when respecting good practices of”
BackgroundTransfer and Vascular Effect of Endothelin Receptor Antagonists in the Human Placenta
Hitzerd, E., Neuman, R. I., Broekhuizen, M., Simons, S. H. P., Schoenmakers, S., Reiss, I. K. M., Koch, B. C. P., van den Meiracker, A. H., Versmissen, J., Visser, W. E., et al. (2019) · Hypertension · doi:10.1161/hypertensionaha.119.14183 · Cited by 24 · see citing works
A Machine Learning Model to Predict Drug Transfer Across the Human Placenta Barrier
Filippo, J. I. D., Bollini, M., & Cavasotto, C. N. (2021) · Frontiers in Chemistry · doi:10.3389/fchem.2021.714678 · Cited by 24 · see citing works
“The fetal-maternal concentration ratio is a widely used indicator of placental permeability that has been applied to drug monitoring (Hutson et al., 2011).”
BackgroundMethodInfluentiall-arginine prevents hypoxia-induced vasoconstriction in dual-perfused human placental cotyledons
Bednov, A. A., Espinoza, J., Betancourt, A., Vedernikov, Y. P., Belfort, M. A., & Yallampalli, C. (2015) · Placenta · doi:10.1016/j.placenta.2015.08.012 · Cited by 24 · see citing works
“[32] was used in this study.”
Opportunities and Challenges for PBPK Model of mAbs in Paediatrics and Pregnancy
Gill, K. L., & Jones, H. M. (2022) · The AAPS Journal · doi:10.1208/s12248-022-00722-0 · Cited by 24 · see citing works
“Ex vivo placental transfer data correlates with in vivo cord:maternal ratio for small molecule drugs [122].”
BackgroundDong, M., Ware, R. E., Dallmann, A., & Vinks, A. A. T. M. M. (2023) · Pharmacotherapy The Journal of Human Pharmacology and Drug Therapy · doi:10.1002/phar.2793 · Cited by 24 · see citing works
van der Zande, I. S. E., van der Graaf, R., Browne, J. L., & van Delden, J. J. M. (2016) · Research ethics forum · doi:10.1007/978-3-319-26512-4_5 · Cited by 23 · see citing works
“To illustrate this point, placental perfusion experiments can be used to predict placental drug transfer and could facilitate the assessment of the risks and potential benefits of drug therapy in pregnancy in the pre-clinical phases of research (Myren et al. 2007; Hutson et al. 2011).”
In silico assessment of risks associated with pesticides exposure during pregnancy
Sobańska, A. W. (2023) · Chemosphere · doi:10.1016/j.chemosphere.2023.138649 · Cited by 22 · see citing works
Endothelin-1 traps as a potential therapeutic tool: from diabetes to beyond?
Jain, A., Coffey, C. G., Mehrotra, V., & Flammer, J. (2019) · Drug Discovery Today · doi:10.1016/j.drudis.2019.07.008 · Cited by 22 · see citing works
Maternal–fetal transfer of indocyanine green across the perfused human placenta
Rubinchik‐Stern, M., Shmuel, M., Bar, J., Eyal, S., & Kovo, M. (2016) · Reproductive Toxicology · doi:10.1016/j.reprotox.2016.04.017 · Cited by 22 · see citing works
Placental transport of parabens studied using an ex-vivo human perfusion model
Andersen, M. H. G., Zuri, G., Knudsen, L. E., & Mathiesen, L. (2021) · Placenta · doi:10.1016/j.placenta.2021.09.010 · Cited by 20 · see citing works
Paulzen, M., Goecke, T. W., Kuzin, M. I., Augustin, M., Gründer, G., & Schoretsanitis, G. (2017) · Schizophrenia Research · doi:10.1016/j.schres.2017.09.043 · Cited by 21 · see citing works
“Placental transfer is particularly affected by the physicochemical properties of a drug (Hutson et al., 2011).”
Prediction of human fetal–maternal blood concentration ratio of chemicals
Wang, C., Lin, P., Chou, C.-Y., Wang, S., & Tung, C.-W. (2020) · PeerJ · doi:10.7717/peerj.9562 · Cited by 20 · see citing works
“Most importantly, the results from in vitro and ex vivo methods are not able to directly predict in vivo outcomes making the assessment of placental transfer difficult (Hutson et al., 2011).”
BackgroundKuoni, S., Steiner, R., Saleh, L., Lehmann, R., Ochsenbein‐Kölble, N., & Simões‐Wüst, A. P. (2024) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2024.116177 · Cited by 19 · see citing works
Kinetics of maternal–fetal drug transfer
Anup, N., Desai, N., Rajpoot, K., & Tekade, R. K. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-814425-1.00007-3 · Cited by 19 · see citing works
van Hove, H., Mathiesen, L., Freriksen, J. J. M., Vähäkangas, K., Colbers, A. P. H., Brownbill, P., & Greupink, R. (2022) · Placenta · doi:10.1016/j.placenta.2022.03.128 · Cited by 19 · see citing works
“Secondly, human placental perfusion, especially after adjusting for protein binding, reflects the in vivo transfer very well in most cases [33], implicating human placental perfusion as a useful tool in preclinical assessment of new antiepileptics.”
BackgroundResultFetal and Perinatal Exposure to Drugs and Chemicals: Novel Biomarkers of Risk
Etwel, F., Hutson, J. R., Madadi, P., Gareri, J., & Koren, G. (2013) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-011613-135930 · Cited by 19 · see citing works
Self-citationBahmanyar, E. R., Out, H. J., & van Duin, M. (2021) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2021.03.024 · Cited by 19 · see citing works
- Authors
- Hutson, J. R., Garcia-Bournissen, F., Davis, A., & Koren, G.
- Affiliations
- University of Toronto (CA)
- Hospital for Sick Children (CA)
- Corresponding author
- Koren, G
- ORCID
- Venue
- Clinical Pharmacology & Therapeutics
- Publisher
- Wiley
- Published
- 2011-05-11
- Volume
- 90
- Issue
- 1
- Pages
- 67-76
- ISSN
- 0009-9236 (ISSN-L)
- 1532-6535
- OpenAlex
- W2069218640
- Cited by
- 199
- References
- 61
- Citations by year
- 2026: 14 · 2025: 9 · 2024: 9 · 2023: 14 · 2022: 15 · 2021: 21 · 2020: 18 · 2019: 16 · 2018: 9 · 2017: 12 · 2016: 13 · 2015: 12 · 2014: 8 · 2013: 13 · 2012: 12
- FWCI
- 1.79
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Pharmacology & Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Canadian Institutes of Health Research
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Pregnancy and Medication Impact
- Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmaceutical studies and practices
- Keywords
- maternal-fetal drug transfer, pharmacokinetic modeling, protein binding, blood pH, drug safety in pregnancy, in vivo prediction
- MeSH terms
- Adult, Data Interpretation, Statistical, Pharmaceutical Preparations, Female, Fetal Blood, Humans, Infant, Newborn, Maternal-Fetal Exchange, Models, Biological, Perfusion, Placenta, Pregnancy, Regional Blood Flow, Models, Statistical, In Vitro Techniques
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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