The DOI matches its Crossref record; 38 of the 38 references it cites were found in a registry or an index.
General approach for the calculation of tissue to plasma partition coefficients
Abstract
A new mechanistic, universal model for the calculation of steady state tissue:plasma partition coefficients (Kt:p) of organic chemicals in mammalian species was developed. The approach allows the estimation of Kt:p-values based on the composition of the tissues in terms of water, neutral lipids, neutral and acidic phospholipids and proteins using the lipophilicity, the binding to phospholipid membranes, the pKa and the unbound fraction in blood plasma as compound specific parameters. Taking explicitly into account the sign and fraction of the charge of the compounds at the physiological pH the method is universally applicable to neutral, acidic, basic or multiply charged substances and has thus a significantly extended applicability compared to previously published approaches. The model was applied to 59 chemically diverse drug compounds for which tissue:plasma partition coefficients are reported in the literature. In total 474 experimentally observed Kt:p values for 12 tissues and the red blood cells were available and could be compared to model results. For 73% of the calculated values a deviation less than 3-fold from the respective observed value was found, proving the validity of the approach.
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“In addition to the mechanistic models available in Simcyp for estimation of K p values, the PK‐Sim standard 45 and Schmitt 46 models can be applied in PK‐Sim.”
From Does the choice of applied physiologically‐based pharmacokinetics platform matter? A case study on simvastatin disposition and drug–drug interaction (2022) · cites this paper as [46]
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Basic Concepts in Physiologically Based Pharmacokinetic Modeling in Drug Discovery and Development
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“However, there are mixed and mechanistic approaches with tolerable error ranges (Poulin and Theil 2002, 2009; Schmitt 2008).”
BackgroundApplied Concepts in PBPK Modeling: How to Build a PBPK/PD Model
Kuepfer, L., Niederalt, C., Wendl, T., Schlender, J., Willmann, S., Lippert, J., Block, M., Eissing, T., & Teutonico, D. (2016) · CPT: Pharmacometrics & Systems Pharmacology · doi:10.1002/psp4.12134 · Cited by 425
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Metadata
- Authors
- Schmitt, W.
- Affiliations
- Bayer (Germany) (DE)
- Corresponding author
- Schmitt, Walter
- ORCID
- Schmitt, Walter
- Venue
- Toxicology in Vitro
- Publisher
- Elsevier BV
- Published
- 2008-03
- Volume
- 22
- Issue
- 2
- Pages
- 457-467
- ISSN
- 0887-2333 (ISSN-L)
- OpenAlex
- W2026015795
- Cited by
- 349
- References
- 38
- Citations by year
- 2026: 16 · 2025: 32 · 2024: 19 · 2023: 34 · 2022: 39 · 2021: 33 · 2020: 20 · 2019: 20 · 2018: 16 · 2017: 25 · 2016: 15 · 2015: 14 · 2014: 13 · 2013: 16 · 2012: 17
- FWCI
- 3.90
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Toxicology in Vitro (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Drug Discovery › Computational Drug Discovery Methods
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Interaction Studies and Fluorescence Analysis
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Keywords
- tissue-to-plasma partition coefficient, organic compounds, lipophilicity, tissue composition, pKa, drug compounds, mechanistic model, erythrocytes
- MeSH terms
- Algorithms, Animals, Chemistry, Physical, Hydrogen-Ion Concentration, Lipids, Phospholipids, Plasma, Proteins, Tissue Distribution, Models, Statistical, Xenobiotics, Extracellular Fluid, Rats, Chemical Phenomena
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