Dose proportionality and bioavailability of quinoxaline-based JNK inhibitor after single oral and intravenous administration in rats; Xenobiotica; Vol. 54, iss. 1

Dose proportionality and bioavailability of quinoxaline-based JNK inhibitor after single oral and intravenous administration in rats

التفاصيل البيبلوغرافية
Parent link:Xenobiotica.— .— London: Taylor & Francis Group
Vol. 54, iss. 1.— 2024.— P. 18-25
مؤلف مشترك: National Research Tomsk Polytechnic University
مؤلفون آخرون: Frelikh G. A. Galina Andreevna, Yanovskaya E. A. Elena Anatoljevna, Lakeev A. P. Aleksandr Pavlovich, Chernysheva G. A., Smolyakova V. I. Vera Ivanovna, Kovrizhina A. R. Anastasia Ruslanovna
الملخص:Title screen
The dose proportionality and bioavailability of the potential anti-inflammatory and neuroprotective JNK inhibitor 11H-indeno[1,2-b]quinoxalin-11-one oxime (IQ-1) were evaluated by comparing pharmacokinetic parameters after single oral (25, 50 and 100 mg/kg) and intravenous (1 mg/kg) IQ-1 administration in rats. IQ-1 and its major metabolite ketone 11H-indeno[1,2-b]quinoxalin-11-one (IQ-18) were isolated from plasma samples by liquid–liquid extraction. IQ-1 (E-isomer) and IQ-18 were simultaneously quantified in plasma by the validated method of liquid chromatography with triple quadrupole mass spectrometry (HPLC–MS/MS). The absolute bioavailability of IQ-1 was < 1.5%. Cmax values were 24.72 ± 4.30, 25.66 ± 7.11 and 37.61 ± 3.53 ng/mL after single oral administration of IQ-1 at doses of 25, 50 and 100 mg/kg, respectively. IQ-1 exhibited dose proportionality at 50–100 mg/kg dose levels, whereas its pharmacokinetics was not dose proportional over the range of 25–50 mg/kg. IQ-18 demonstrated the invariance of the dose-normalized Cmax. In this study we systematically elucidated the absorption characteristics of IQ-1 in rat gastrointestinal tract and provided better understanding of IQ-1 pharmacology for the future development of a new formulations and therapeutic optimisation.
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اللغة:الإنجليزية
منشور في: 2024
الموضوعات:
электронный ресурс
труды учёных ТПУ
bioavailability
dose proportionality
preclinical pharmacokinetics
liquid chromatography-mass spectrometry
absorption
الوصول للمادة أونلاين:https://doi.org/10.1080/00498254.2023.2299686
التنسيق: الكتروني فصل الكتاب
KOHA link:https://koha.lib.tpu.ru/cgi-bin/koha/opac-detail.pl?biblionumber=672937

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