ArticleThe AAPS journal2022
Multi-Well Array Culture of Primary Human Hepatocyte Spheroids for Clearance Extrapolation of Slowly Metabolized Compounds.
Article in The AAPS journal, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 33 citations in OpenAlex.
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- Animal product-free formation and cultivation of three-dimensional primary hepatocyte spheroids.Drug metabolism and disposition: the biological fate of chemicals · 2025Article
- Quantifying expression and metabolic activity of genes regulated by pregnane X receptor in primary human hepatocyte spheroids.PLoS computational biology · 2025Article
- In Vitro Hepatic Metabolism Input Parameters Support Toxicokinetic Simulations for the Formation of Methoxy Propionic Acid From β-Isomer Propylene Glycol Methyl Ether.Pharmacology research & perspectives · 2024Article
- The Current State of Biotransformation Science - Industry Survey of In Vitro and In Vivo Practices, Clinical Translation, and Future Trends.Pharmaceutical research · 2024Article
- OCT1 (SLC22A1) transporter kinetics and regulation in primary human hepatocyte 3D spheroids.Scientific reports · 2024Article
- In silico modeling and simulation of organ-on-a-chip systems to support data analysis and a priori experimental design.CPT: pharmacometrics & systems pharmacology · 2024Article
- Compound Absorption in Polymer Devices Impairs the Translatability of Preclinical Safety Assessments.Advanced healthcare materials · 2024Article
- Novel Strategy to Assess the Neurotoxicity of Organic Solvents Such as Glycol Ethers: Protocol for Combining In Vitro and In Silico Methods With Human-Controlled Exposure Experiments.JMIR research protocols · 2024Article
- Bioengineered Pancreas-Liver Crosstalk in a Microfluidic Coculture Chip Identifies Human Metabolic Response Signatures in Prediabetic Hyperglycemia.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Setup of human liver-chips integrating 3D models, microwells and a standardized microfluidic platform as proof-of-concept study to support drug evaluation.Biomaterials and biosystems · 2022Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Accurate prediction of human pharmacokinetics using in vitro tools is an important task during drug development. Albeit, currently used in vitro systems for clearance extrapolation such as microsomes and primary human hepatocytes in suspension culture show reproducible turnover, the utility of these systems is limited by a rapid decline of activity of drug metabolizing enzymes. In this study, a multi-well array culture of primary human hepatocyte spheroids was compared to suspension and single spheroid cultures from the same donor. Multi-well spheroids remained viable and functional over the incubation time of 3 days, showing physiological excretion of albumin and α-AGP. Their metabolic activity was similar compared to suspension and single spheroid cultures. This physiological activity, the high cell concentration, and the prolonged incubation time resulted in significant turnover of all tested low clearance compounds (n = 8). In stark contrast, only one or none of the compounds showed significant turnover when single spheroid or suspension cultures were used. Using multi-well spheroids and a regression offset approach (log(CL
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Registered trials
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