Tabriz University of Medical Sciences Pharmaceutical Sciences 1735-403X 32 4 2026 10 31 Biodisposition of the Promising JNK Inhibitor IQ-1 and its Metabolite in Rats Following Single Oral Administration 611 622 10.34172/ps.43665 EN Galina A. Frelikh https://orcid.org/0000-0003-3543-1540 Elena A. Yanovskaya https://orcid.org/0000-0002-4635-8046 Alexander P. Lakeev https://orcid.org/0000-0003-4597-3378 Galina A. Chernysheva https://orcid.org/0000-0002-6438-5734 Vera I. Smolyakova https://orcid.org/0000-0001-9501-4664 Andrei I. Khlebnikov https://orcid.org/0000-0002-3022-4510 Journal Article 10.34172/ps.43665 2025 12 23 2026 06 08 Introduction: The JNK inhibitor 11H-indeno[1,2-b]quinoxalin-11-one oxime (IQ-1) and its sodium salt exhibit antioxidant, hemorheological, endothelium-protective, anti-inflammatory, neuroprotective, and cardioprotective properties; however, no published reports describe their tissue distribution. We investigated the biodisposition of IQ-1 and its major metabolite, 11H-indeno[1,2-b]quinoxalin-11-one (IQ-18), in Wistar rats after a single oral 50 mg/kg dose of IQ-1. Methods: Male adult Wistar rats (230–260 g) received IQ-1 orally (50 mg/kg). To investigate plasma pharmacokinetics and tissue distribution of IQ-1 and its metabolite IQ-18 in rats, arterial blood was collected from the carotid artery, and tissue samples (liver, kidney, heart, brain, lung, spleen, skeletal muscle, adipose tissue, and duodenum) were harvested following oral administration of 50 mg/kg IQ-1. Mesenteric lymph, bile, and blood from the portal vein and inferior vena cava were also obtained post-dose to clarify the absorption routes and metabolic sites of IQ-1. Chromatographic separation was carried out on an EC Nucleodur C8 ec LC column (150×4.6 mm, 5 µm; Macherey-Nagel, Germany). IQ-1 and IQ-18 were quantified by validated LC-MS/MS method using a LC-20 Prominence system (Shimadzu) and a mass spectrometer 3200 QTRAP (AB Sciex). Analyst 1.6 and MultiQuant 2.1 (AB Sciex) handled data acquisition and analysis. Non-compartmental pharmacokinetic parameters were calculated with WinNonlin 5.2 (Pharsight). Statistics (Mann–Whitney U test; P<0.05) were performed in Statistica 12. Results: The plasma pharmacokinetic parameters for IQ-1 were as follows: Cmax, 59.69 ng/mL; Tmax, 1 h; and T1/2, 5.58 h. IQ-1 was metabolized to IQ-18, which reached a plasma Cmax of 2464.06 ng/mL at 8 h. Both compounds were widely distributed in tissues, with the highest tissue-to-plasma ratio observed in the liver. The Tmax values were 0.5–1 h for IQ-1 and 4–8 h for IQ-18. These data may indicate predominant absorption via the portal vein, extensive hepatic metabolism, and a substantial reduction in the concentrations of both compounds in venous blood following hepatic passage. Conclusion: Our results provide valuable insights into the pharmacokinetic profile of IQ-1, which may inform future clinical trials.