Pharmacokinetics and apparent Michaelis constant for metabolite conversion of sorafenib in healthy and hepatocellular carcinoma-bearing rats
Aim: Investigation of the pharmacokinetics of sorafenib (SRF) in rats with hepatocellular carcinoma (HCC). Methods: A reproducible ultra-HPLC-MS method for simultaneous determination of serum SRF, N-hydroxymethyl sorafenib and N-demethylation sorafenib. Results: Both the maximum serum concentrations (2.5-times) and the area under the serum concentration-time curve from 0 h to infinity (4.5-times) of SRF were observed to be significantly higher, with a greater than 3.0-fold decrease in the clearance rate in the HCC-bearing rats compared with these values in healthy animals. Further study revealed approximately 3.8- and 3.2-times increases in the apparent Michaelis constant for N-hydroxymethyl sorafenib and N-demethylation sorafenib conversions in the HCC-bearing rats. Conclusion: The low efficiency for the SRF conversions was a key contributor to the increased serum concentrations of SRF.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
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| Enthalten in: |
Bioanalysis - (2024) vom: 26. März |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Cai, Hongxin [VerfasserIn] |
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| Links: |
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| Themen: |
Hepatocellular carcinoma |
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| Anmerkungen: |
Date Revised 26.03.2024 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.4155/bio-2023-0215 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM37019778X |
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| 245 | 1 | 0 | |a Pharmacokinetics and apparent Michaelis constant for metabolite conversion of sorafenib in healthy and hepatocellular carcinoma-bearing rats |
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| 520 | |a Aim: Investigation of the pharmacokinetics of sorafenib (SRF) in rats with hepatocellular carcinoma (HCC). Methods: A reproducible ultra-HPLC-MS method for simultaneous determination of serum SRF, N-hydroxymethyl sorafenib and N-demethylation sorafenib. Results: Both the maximum serum concentrations (2.5-times) and the area under the serum concentration-time curve from 0 h to infinity (4.5-times) of SRF were observed to be significantly higher, with a greater than 3.0-fold decrease in the clearance rate in the HCC-bearing rats compared with these values in healthy animals. Further study revealed approximately 3.8- and 3.2-times increases in the apparent Michaelis constant for N-hydroxymethyl sorafenib and N-demethylation sorafenib conversions in the HCC-bearing rats. Conclusion: The low efficiency for the SRF conversions was a key contributor to the increased serum concentrations of SRF | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Michaelis constant | |
| 650 | 4 | |a hepatocellular carcinoma | |
| 650 | 4 | |a metabolism | |
| 650 | 4 | |a pharmacokinetics | |
| 650 | 4 | |a sorafenib | |
| 700 | 1 | |a Du, Xiaoyue |e verfasserin |4 aut | |
| 700 | 1 | |a Deng, Yufeng |e verfasserin |4 aut | |
| 700 | 1 | |a Cao, Dejian |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Lele |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Zhiguo |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Xianchao |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Jinbiao |e verfasserin |4 aut | |
| 700 | 1 | |a Xie, Baogang |e verfasserin |4 aut | |
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