Towards human ex vivo organ perfusion models to elucidate drug pharmacokinetics in health and disease
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 of ADME profiles earlier in the drug development process are very valuable. Good prediction of intestinal absorption and renal and biliary excretion remain especially difficult, as there is an interplay of active transport and metabolism involved. To study these processes, including enterohepatic circulation, ex vivo tissue models are highly relevant and can be regarded as the bridge between in vitro and in vivo models. In this review the current in vitro, in vivo and in more detail ex vivo models for studying pharmacokinetics in health and disease are discussed. Additionally, we propose novel models, i.e., perfused whole-organs, which we envision will generate valuable pharmacokinetic information in the future due to improved translation to the in vivo situation. These machine-perfused organ models will be particularly interesting in combination with biomarkers for assessing the functionality of transporter and CYP450 proteins.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:52 |
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| Enthalten in: |
Drug metabolism reviews - 52(2020), 3 vom: 03. Aug., Seite 438-454 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Stevens, Lianne J [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 30.06.2021 Date Revised 30.06.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1080/03602532.2020.1772280 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM311307167 |
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| 245 | 1 | 0 | |a Towards human ex vivo organ perfusion models to elucidate drug pharmacokinetics in health and disease |
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| 500 | |a Date Completed 30.06.2021 | ||
| 500 | |a Date Revised 30.06.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 of ADME profiles earlier in the drug development process are very valuable. Good prediction of intestinal absorption and renal and biliary excretion remain especially difficult, as there is an interplay of active transport and metabolism involved. To study these processes, including enterohepatic circulation, ex vivo tissue models are highly relevant and can be regarded as the bridge between in vitro and in vivo models. In this review the current in vitro, in vivo and in more detail ex vivo models for studying pharmacokinetics in health and disease are discussed. Additionally, we propose novel models, i.e., perfused whole-organs, which we envision will generate valuable pharmacokinetic information in the future due to improved translation to the in vivo situation. These machine-perfused organ models will be particularly interesting in combination with biomarkers for assessing the functionality of transporter and CYP450 proteins | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Review | |
| 650 | 4 | |a Preclinical models | |
| 650 | 4 | |a biliary and renal secretion | |
| 650 | 4 | |a drug-drug interactions | |
| 650 | 4 | |a endogenous biomarkers | |
| 650 | 4 | |a perfusion models | |
| 650 | 4 | |a pharmacokinetics | |
| 650 | 7 | |a Biomarkers, Pharmacological |2 NLM | |
| 650 | 7 | |a Membrane Transport Proteins |2 NLM | |
| 650 | 7 | |a Pharmaceutical Preparations |2 NLM | |
| 700 | 1 | |a Donkers, Joanne M |e verfasserin |4 aut | |
| 700 | 1 | |a Dubbeld, Jeroen |e verfasserin |4 aut | |
| 700 | 1 | |a Vaes, Wouter H J |e verfasserin |4 aut | |
| 700 | 1 | |a Knibbe, Catherijne A J |e verfasserin |4 aut | |
| 700 | 1 | |a Alwayn, Ian P J |e verfasserin |4 aut | |
| 700 | 1 | |a van de Steeg, Evita |e verfasserin |4 aut | |
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