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Eslami Amirabadi, H. (author), Donkers, J.M. (author), Wieringa, E. (author), Ingenhut, B. (author), Pieters, L. (author), Stevens, L. (author), Donkers, T. (author), Westerhout, J. (author), Masereeuw, R. (author), Bobeldijk-Pastorova, I. (author), Nooijen, I. (author), van de Steeg, E. (author)The majority of intestinal in vitro screening models use cell lines that do not reflect the complexity of the human intestinal tract and hence often fail to accurately predict intestinal drug absorption. Tissue explants have intact intestinal architecture and cell type diversity, but show short viability in static conditions. Here, we present a...article 2022
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Streekstra, E.J. (author), Kiss, M. (author), van den Heuvel, J. (author), Nicolaï, J. (author), van den Broek, P. (author), Botden, S.M.B.I. (author), Stommel, M.W.J. (author), van Rijssel, L. (author), Ungell, A.L. (author), van de Steeg, E. (author), Russel, F.G.M. (author), de Wildt, S.N. (author)Little is known about the impact of age on the processes governing human intestinal drug absorption. The Ussing chamber is a system to study drug transport across tissue barriers, but it has not been used to study drug absorption processes in children. This study aimed to explore the feasibility of the Ussing chamber methodology to assess...article 2022
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Donkers, J.M. (author), Hoppener, E.M. (author), Grigoriev, I. (author), Will, L. (author), Melgert, B.N. (author), van der Zaan, B. (author), van de Steeg, E. (author), Kooter, I.M. (author)Micro- and nanoplastics (MNP) can be found virtually everywhere around us in the biosphere and food chain, therefore humans are continuously exposed to MNP, mainly via inhalation and ingestion. Here, we have applied physiologically relevant human-based advanced in vitro models representing the lung (MucilAir™) and gut (InTESTine™ and Intestinal...article 2022
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Donkers, J.M. (author), Eslami Amirabadi, H. (author), van de Steeg, E. (author)Over the past decade, microfluidic intestine-on-a-chip models have been emerging as a novel platform to study intestinal function in health and disease. These microphysiological systems surpass conventional in vitro intestinal model systems, as they add microenvironmental context in the form of mechanical cues or by the incorporation of multiple...article 2021
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van Berlo, D. (author), van de Steeg, E. (author), Amirabadi, H.E. (author), Masereeuw, R. (author)The development of new medicines suffers from attrition, especially in the development pipeline. Eight out of nine drug candidates entering the clinical testing phase fail, mostly due to poor safety and efficacy. The low predictive value of animal models, used in earlier phases of drug development, for effects in humans poses a major problem. In...article 2021
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Stevens, L.J. (author), Zhu, A.Z.X. (author), Chothe, P.P. (author), Chowdhury, S.K. (author), Donkers, J.M. (author), Vaes, W.H.J. (author), Knibbe, C.A.J. (author), Alwayn, I.P.J. (author), van de Steeg, E. (author)There is a lack of translational preclinical models that can predict hepatic handling of drugs. In this study we aimed to evaluate the applicability of normothermic machine perfusion (NMP) of porcine livers as a novel ex vivo model to predict hepatic clearance, biliary excretion and plasma exposure of drugs. For this evaluation we dosed...article 2021
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Streekstra, E.J. (author), Russel, F.G.M. (author), van de Steeg, E. (author), de Wildt, S.N. (author)Drug disposition in children is different compared to adults. Growth and developmental change the processes involved in drug disposition and efficacy, including membrane transporters and drug metabolizing enzymes, but for many of these proteins, the exact changes have not been fully elucidated to date. Quantitative proteomics offers a solution...article 2021
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Rahman, S. (author), Ghiboud, M. (author), Donkers, J.M. (author), van de Steeg, E. (author), van Tol, E.A.F. (author), Hakvoort, T.B.M. (author), de Jonge, W.J. (author)Over the past years, several preclinical in vitro and ex vivo models have been developed that helped to understand some of the critical aspects of intestinal functions in health and disease such as inflammatory bowel disease (IBD). However, the translation to the human in vivo situation remains problematic. The main reason for this is that these...article 2021
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Stevens, L.J. (author), Donkers, J.M. (author), Dubbel, J. (author), Vaes, W.H.J. (author), van de Steeg, E. (author), Knibbe, C.A.J. (author), Alwayn, I.P.J. (author), van de Steeg, E. (author)To predict the absorption, distribution, metabolism and excretion (ADME) profile of candidate drugs a variety of preclinical models can be applied. The ADME and toxicological behavior of newly developed drugs are often investigated prior to assessment in humans, which is associated with long time-lines and high costs. Therefore, good predictions...article 2020
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- Bouwmeester, H. (author), Withoff, S. (author), van de Steeg, E. (author) bookPart 2020
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Stevens, L.J. (author), van Lipzig, M.M.H. (author), Erpelinck, S.L.A. (author), Pronk, A. (author), van Gorp, J. (author), Wortelboer, H.M. (author), van de Steeg, E. (author)A majority of the preclinical intestinal screening models do not properly reflect the complex physiology of the human intestinal tract, resulting in low translational value to the clinical situation. The often used cell lines such as Caco-2 or HT-29 are not well suited to investigate the different processes that predict oral bioavailability in...article 2019
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van der Heiden, M.S. (author), Tejeda, H. (author), Rajadurai, S.R.S. (author), Donkers, T. (author), Duivenvoorde, T.L.P. (author), Eslami Amirabadi, H. (author), Ananth, A.N. (author), Lucas, P. (author), van de Steeg, E. (author)Organ-on-chip technology is based on tissues or (stem)cell derived organ mimicking structures and in microfluidic systems. This technology is used to monitor functional response to stimuli, aiming to enable personalized medicine and to conduct pre-clinical drug development studies. In general, cells in stress exhibit a change in nanomechanical...other 2019
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Peters, V.B.M. (author), van de Steeg, E. (author), van Bilsen, J. (author), Meijerink, M. (author)The human body is exposed to many xenobiotic, potentially harmful compounds. The intestinal immune system is crucial in protecting the human body from these substances. Moreover, many microorganisms, residing in the gastrointestinal tract, play an important role in modulating immune responses. Pre- and probiotics may have beneficial effects on...article 2019
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Eslami Amirabadi, H. (author), Wierenga, E. (author), Stevens, L.J. (author), Donkers, J. (author), Donkers, T. (author), Ingenhut, B.L.J. (author), Usta, B. (author), Pieters, L. (author), Gröllers, M. (author), Nooijen, I.H.G. (author), Erpelinck, S.L.A. (author), Schuren, F. (author), Masereeuw, R. (author), van de Steeg, E. (author)The majority of screening and predictive models do not reflect the physiology of the human intestinal tract since they show major limitations to include the processes that determine the oral bioavailability1,2. A major drawback of current intestinal models is the use of single cell lines and the static environment, which is in contrast with the...public lecture 2019
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Stevens, L. (author), Dubbeld, J. (author), Doppenberg, J. (author), Erpelinck, S. (author), Knibbe, C. (author), Alwayn, I. (author), van de Steeg, E. (author)Current models to predict biliary excretion often fail due to species differences (rodent/dog) or due to differences in transporter expression in in vitro assays (e.g. sandwich cultured hepatocytes). Especially when drugs are subjective to enterohepatic circulation (EHC), this results difficulties to predict plasma profiles after oral and iv...public lecture 2019
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van de Steeg, E. (author), Schuren, F.H.J. (author), Nooijen, I.H.G. (author), Erpelinck, S. (author), Scott Obach, R. (author), Vaes, W.H.J. (author)Gut microbiota plays a major role in metabolizing xenobiotics into active, inactive or toxic metabolites, thereby influencing pharmacokinetics, efficacy and toxicity profiles of prescribed drugs, which is currently being underexplored.public lecture 2019
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van de Steeg, E. (author), Schuren, F.H.J. (author), Obach, R.S. (author), van Woudenbergh, C. (author), Walker, G.S. (author), Heerikhuisen, M. (author), Nooijen, I.H.G. (author), Vaes, W.H.J. (author)Colon microbiota-based drug metabolism has received little attention thus far in the process of drug development, whereas the role of gut microbiota in clinical safety and efficacy of drugs has become more clear. Many of these studies have been performed using animal studies, but the translational value of these data with respect to drug...article 2018
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van Groen, B.D. (author), van de Steeg, E. (author), Mooij, M.G. (author), van Lipzig, M.M.H. (author), de Koning, B.A.E. (author), Verdijk, R.M. (author), Wortelboer, H.M. (author), Gaedigk, R. (author), Bi, C. (author), Leeder, S. (author), van Schaik, R.H.N. (author), van Rosmalen, J. (author), Tibboel, D. (author), Vaes, W.H. (author), de Wildt, S.N. (author)Background Hepatic membrane transporters are involved in the transport of many endogenous and exogenous compounds, including drugs. We aimed to study the relation of age with absolute transporter protein expression in a cohort of 62 mainly fetus and newborn samples. Methods Protein expressions of BCRP, BSEP, GLUT1, MCT1, MDR1, MRP1, MRP2, MRP3,...article 2018
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Notenboom, S. (author), Weigand, K.M. (author), Proost, J.H. (author), van Lipzig, M.M. (author), van de Steeg, E. (author), van den Broek, P.H.H. (author), Greupink, R. (author), Russel, F.G.M. (author), Groothuis, G.M.M. (author)The authors regret the molar unit is incorrectly displayed on the x-axis in Fig. 4A and 4C and on the y-axis in Fig. 4B, 4D and Fig. 5. The correct versions of the figures are displayed below together with the unchanged legends. The authors would like to apologise for any inconvenience caused. DOI of original article: 10.1016/j.ejps.2018.01.007 ...article 2018
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Notenboom, S. (author), Weigand, K.M. (author), Proost, J.H. (author), van Lipzig, M.M.H. (author), van de Steeg, E. (author), van den Broek, P.H.H. (author), Greupink, R. (author), Russel, F.G.M. (author), Groothuis, G.M.M. (author)Drug-induced liver injury (DILI) is a common reason for drug withdrawal from the market. An important cause of DILI is drug-induced cholestasis. One of the major players involved in drug-induced cholestasis is the bile salt efflux pump (BSEP; ABCB11). Inhibition of BSEP by drugs potentially leads to cholestasis due to increased (toxic)...article 2018
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