Abstract
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.
Acknowledgements
Authors appreciate the employees of the Kizhner Scientific Center for supplying substances (IQ-1 and IQ-18) and general consulting.
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Disclosure statement
No potential conflict of interest was reported by the author(s).
Data availability statement
All data generated or analysed during this study are included in this article. The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.