Pharmacokinetics and metabolism of mirogabalin, a novel α2δ ligand, in rats and monkeys / Naotoshi Yamamura, Minoru Uchiyama, Makoto Takahashi, Tomoyo Honda, Yumi Nishiya
Abstract The purpose of this study was to investigate the pharmacokinetic behaviour of mirogabalin in rats and monkeys. Pharmacokinetic parameters of mirogabalin after its oral and intravenous administration were determined. Distribution study, mass balance study, and metabolite identification were also conducted after the oral administration of [ 14 C]mirogabalin. Plasma exposure ( C max and AUC inf ) increased dose-proportionally after the oral administration of mirogabalin at 1, 3, and 10 mg/kg to rats and monkeys. Mean total body clearance (CL tot ) after intravenous administration at 3 mg/kg was 13.5 mL/min/kg in rats and 9.02 mL/min/kg in monkeys, and absolute bioavailability at 3 mg/kg was 97.6% in rats and 85.2% in monkeys. There was a greater recovery of radioactivity in urine than that in faeces after the oral administration of [ 14 C]mirogabalin. The main radioactive component in the plasma, urine, and faeces was mirogabalin. A204-4455 (lactam form), an oxidised metabolite of mirogabalin, mirogabalin N -glucuronide and O -glucuronide of oxidised A204-4455 were detected as minor components in monkeys and rats. Mirogabalin administered orally was almost completely eliminated via urinary excretion. A small part of the orally administered dose of mirogabalin was metabolised via glucuronidation at the amine and carboxylic acid moiety and oxidation as the primary metabolic pathway.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:52 |
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| Enthalten in: |
Xenobiotica - 52(2022), 1, Seite 54-64 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Yamamura, Naotoshi [VerfasserIn] |
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| Links: |
FID Access [lizenzpflichtig] |
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| Themen: |
Disproportional metabolite |
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| Umfang: |
1 Online-Ressource (11 p) |
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| doi: |
10.1080/00498254.2022.2049396 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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KFL011135263 |
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| 245 | 1 | 0 | |a Pharmacokinetics and metabolism of mirogabalin, a novel α2δ ligand, in rats and monkeys |c Naotoshi Yamamura, Minoru Uchiyama, Makoto Takahashi, Tomoyo Honda, Yumi Nishiya |
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| 520 | |a Abstract The purpose of this study was to investigate the pharmacokinetic behaviour of mirogabalin in rats and monkeys. Pharmacokinetic parameters of mirogabalin after its oral and intravenous administration were determined. Distribution study, mass balance study, and metabolite identification were also conducted after the oral administration of [ 14 C]mirogabalin. Plasma exposure ( C max and AUC inf ) increased dose-proportionally after the oral administration of mirogabalin at 1, 3, and 10 mg/kg to rats and monkeys. Mean total body clearance (CL tot ) after intravenous administration at 3 mg/kg was 13.5 mL/min/kg in rats and 9.02 mL/min/kg in monkeys, and absolute bioavailability at 3 mg/kg was 97.6% in rats and 85.2% in monkeys. There was a greater recovery of radioactivity in urine than that in faeces after the oral administration of [ 14 C]mirogabalin. The main radioactive component in the plasma, urine, and faeces was mirogabalin. A204-4455 (lactam form), an oxidised metabolite of mirogabalin, mirogabalin N -glucuronide and O -glucuronide of oxidised A204-4455 were detected as minor components in monkeys and rats. Mirogabalin administered orally was almost completely eliminated via urinary excretion. A small part of the orally administered dose of mirogabalin was metabolised via glucuronidation at the amine and carboxylic acid moiety and oxidation as the primary metabolic pathway | ||
| 653 | |a Mirogabalin | ||
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| 700 | 1 | |a Nishiya, Yumi |e verfasserin |4 aut | |
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