Absorption, Distribution, Metabolism, and Excretion of [14C]BS1801, a Selenium-Containing Drug Candidate, in Rats
BS1801 is a selenium-containing drug candidate with potential for treating liver and lung fibrosis. To fully elucidate the biotransformation of BS1801 in animals and provide sufficient preclinical drug metabolism data for human mass balance study, the metabolism of BS1801 in rats was investigated. We used radiolabeling techniques to investigate the mass balance, tissue distribution, and metabolite identification of BS1801 in Sprague-Dawley/Long-Evans rats after a single oral dose of 100 mg/kg (100 μCi/kg) [14C]BS1801: 1. The mean recovery of radioactive substances in urine and feces was 93.39% within 168 h postdose, and feces were the main excretion route. 2. Additionally, less than 1.00% of the dose was recovered from either urine or bile. 3. BS1801-related components were widely distributed throughout the body. 4. Fifteen metabolites were identified in rat plasma, urine, feces, and bile, and BS1801 was detected only in feces. 5. BS1801-M484, the methylation product obtained via a N-Se bond reduction in BS1801, was the most abundant drug-related component in plasma. The main metabolic pathways of BS1801 were reduction, amide hydrolysis, oxidation, and methylation. Overall, BS1801 was distributed throughout the body, and excreted mainly as an intact BS1801 form through feces. No differences were observed between male and female rats in distribution, metabolism, and excretion of BS1801.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:28 |
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| Enthalten in: |
Molecules (Basel, Switzerland) - 28(2023), 24 vom: 15. Dez. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Yang, Cheng [VerfasserIn] |
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| Links: |
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| Themen: |
[14C]BS1801 |
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| Anmerkungen: |
Date Completed 25.12.2023 Date Revised 25.12.2023 published: Electronic Citation Status MEDLINE |
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| doi: |
10.3390/molecules28248102 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM366292560 |
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| 245 | 1 | 0 | |a Absorption, Distribution, Metabolism, and Excretion of [14C]BS1801, a Selenium-Containing Drug Candidate, in Rats |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a BS1801 is a selenium-containing drug candidate with potential for treating liver and lung fibrosis. To fully elucidate the biotransformation of BS1801 in animals and provide sufficient preclinical drug metabolism data for human mass balance study, the metabolism of BS1801 in rats was investigated. We used radiolabeling techniques to investigate the mass balance, tissue distribution, and metabolite identification of BS1801 in Sprague-Dawley/Long-Evans rats after a single oral dose of 100 mg/kg (100 μCi/kg) [14C]BS1801: 1. The mean recovery of radioactive substances in urine and feces was 93.39% within 168 h postdose, and feces were the main excretion route. 2. Additionally, less than 1.00% of the dose was recovered from either urine or bile. 3. BS1801-related components were widely distributed throughout the body. 4. Fifteen metabolites were identified in rat plasma, urine, feces, and bile, and BS1801 was detected only in feces. 5. BS1801-M484, the methylation product obtained via a N-Se bond reduction in BS1801, was the most abundant drug-related component in plasma. The main metabolic pathways of BS1801 were reduction, amide hydrolysis, oxidation, and methylation. Overall, BS1801 was distributed throughout the body, and excreted mainly as an intact BS1801 form through feces. No differences were observed between male and female rats in distribution, metabolism, and excretion of BS1801 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a BS1801 (butaselen) | |
| 650 | 4 | |a [14C]BS1801 | |
| 650 | 4 | |a mass balance | |
| 650 | 4 | |a metabolism | |
| 650 | 4 | |a selenium | |
| 650 | 4 | |a tissue distribution | |
| 650 | 7 | |a Selenium |2 NLM | |
| 650 | 7 | |a H6241UJ22B |2 NLM | |
| 700 | 1 | |a Xue, Mingzhen |e verfasserin |4 aut | |
| 700 | 1 | |a He, Yifei |e verfasserin |4 aut | |
| 700 | 1 | |a Yin, Hanwei |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Chen |e verfasserin |4 aut | |
| 700 | 1 | |a Zhong, Dafang |e verfasserin |4 aut | |
| 700 | 1 | |a Zeng, Huihui |e verfasserin |4 aut | |
| 700 | 1 | |a Zheng, Yuandong |e verfasserin |4 aut | |
| 700 | 1 | |a Diao, Xingxing |e verfasserin |4 aut | |
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