Empirical and theoretical approaches for the prediction of human hepatic clearance using chimeric mice with humanised liver: the use of physiologically based scaling, a novel solution for potential overprediction due to coexisting mouse metabolism / Shogo Matsumoto, Hidetaka Kamimura, Megumi Nishiwaki, Naoki Cho, Kazuhiko Kato, Taichi Yamamoto
Abstract Chimeric mice are immunodeficient mice in which the majority of the hepatic parenchymal cells are replaced with human hepatocytes. Following intravenous administration of 24 model compounds to control and chimeric mice, human hepatic clearance (CL h ) was predicted using the single-species allometric scaling (SSS) method. Predictability of the chimeric mice was better than that of the control mice. Human CL h was predicted by the physiologically based scaling (PBS) method, wherein observed CL h in chimeric mice was first converted to intrinsic CL h (CL h,int ). As the liver of chimeric mice contains remaining mouse hepatocytes, CL h,int was corrected by in vitro CL h ratios of the mouse to human hepatocytes according to their hepatocyte replacement index. Further, predicted human CL h was calculated based on an assumption that CL h,int in chimeric mice normalised for their liver weight was equal to CL h,int per liver weight in humans. Consequently, better prediction performance was observed with the use of the PBS method than the SSS method. SSS method is an empirical method, and the effects of coexisting mouse metabolism cannot be avoided. However, the PBS method with in vitro CL h correction might be a potential solution and may expand the application of chimeric mice in new drug development.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2021 |
|---|---|
| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:51 |
|---|---|
| Enthalten in: |
Xenobiotica - 51(2021), 9, Seite 983- |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Matsumoto, Shogo [VerfasserIn] |
|---|
| Links: |
FID Access [lizenzpflichtig] |
|---|
| Umfang: |
1 Online-Ressource (12 p) |
|---|
| doi: |
10.1080/00498254.2021.1950865 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
KFL009133356 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | KFL009133356 | ||
| 003 | DE-627 | ||
| 005 | 20230621210102.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 220511s2021 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1080/00498254.2021.1950865 |2 doi | |
| 035 | |a (DE-627)KFL009133356 | ||
| 035 | |a (KFL)prod_LgpH_10.1080/00498254.2021.1950865 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 084 | |a PHARM |q DE-84 |2 fid | ||
| 100 | 1 | |a Matsumoto, Shogo |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Empirical and theoretical approaches for the prediction of human hepatic clearance using chimeric mice with humanised liver: the use of physiologically based scaling, a novel solution for potential overprediction due to coexisting mouse metabolism |c Shogo Matsumoto, Hidetaka Kamimura, Megumi Nishiwaki, Naoki Cho, Kazuhiko Kato, Taichi Yamamoto |
| 264 | 1 | |c 2021 | |
| 300 | |a 1 Online-Ressource (12 p) | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 520 | |a Abstract Chimeric mice are immunodeficient mice in which the majority of the hepatic parenchymal cells are replaced with human hepatocytes. Following intravenous administration of 24 model compounds to control and chimeric mice, human hepatic clearance (CL h ) was predicted using the single-species allometric scaling (SSS) method. Predictability of the chimeric mice was better than that of the control mice. Human CL h was predicted by the physiologically based scaling (PBS) method, wherein observed CL h in chimeric mice was first converted to intrinsic CL h (CL h,int ). As the liver of chimeric mice contains remaining mouse hepatocytes, CL h,int was corrected by in vitro CL h ratios of the mouse to human hepatocytes according to their hepatocyte replacement index. Further, predicted human CL h was calculated based on an assumption that CL h,int in chimeric mice normalised for their liver weight was equal to CL h,int per liver weight in humans. Consequently, better prediction performance was observed with the use of the PBS method than the SSS method. SSS method is an empirical method, and the effects of coexisting mouse metabolism cannot be avoided. However, the PBS method with in vitro CL h correction might be a potential solution and may expand the application of chimeric mice in new drug development | ||
| 700 | 1 | |a Kamimura, Hidetaka |e verfasserin |4 aut | |
| 700 | 1 | |a Nishiwaki, Megumi |e verfasserin |4 aut | |
| 700 | 1 | |a Cho, Naoki |e verfasserin |4 aut | |
| 700 | 1 | |a Kato, Kazuhiko |e verfasserin |4 aut | |
| 700 | 1 | |a Yamamoto, Taichi |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Xenobiotica |d Abingdon : Taylor & Francis Group, 1971 |g 51(2021), 9, Seite 983- |h Online-Ressource |w (DE-627)KFL000005959 |w (DE-600)1485113-1 |w (DE-576)079719163 |x 1366-5928 |7 nnns |
| 773 | 1 | 8 | |g volume:51 |g year:2021 |g number:9 |g pages:983- |
| 856 | 4 | 0 | |u http://pharmazie.proxy.fid-lizenzen.de/fid/tandf-ejournals-pharmazie/doi.org/10.1080/00498254.2021.1950865 |m X:KFL |x Resolving-System |x Verlag |y FID Access |z lizenzpflichtig |
| 912 | |a ZDB-1-TFE | ||
| 912 | |a GBV_KFL | ||
| 912 | |a FID-PHARM | ||
| 912 | |a SSG-OLC-PHA | ||
| 935 | |i IMPORT_0628_prod_LgpH_02 | ||
| 951 | |a AR | ||
| 952 | |d 51 |j 2021 |e 9 |h 983- | ||