ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Drug Metabolism and Transport
Safety Evaluation and Toxicokinetics of Repeated Inhalation Exposure to Pegylated Interferon α-2b
Provisionally accepted
- 1Department of Pharmacy, Haikou Affiliated Hospital of Central South University Xiangya School of Medicine, Haikou, China
- 2Department of Infectious Diseases, Shanxi Children's Hospital, Taiyuan, China
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This study aimed to evaluate the safety profile and toxicokinetic (TK) characteristics of pegylated interferon α-2b (PEG IFNα-2b) following repeated nebulized inhalation exposure in juvenile Sprague-Dawley (SD) rats, and to establish the no-observed-adverse-effect level (NOAEL) to support its clinical development for pediatric respiratory infections. A total of 190 juvenile SD rats (5–6 days old) were randomized into blank control, low- (126.4 ± 21.8 μg/kg), mid- (384.3 ± 66.9 μg/kg), and high-dose (1202.4 ± 176.4 μg/kg) groups. Animals received nebulized PEG IFNα-2b via whole-body/nasal inhalation once every two days for two consecutive weeks. Assessments included clinical observations, body weight, hematology, coagulation, serum biochemistry, developmental parameters, histopathology, and TK analysis. PEG IFNα-2b was well tolerated at all dose levels, with no treatment-related mortality, clinical signs, or histopathological alterations observed. Systemic exposure increased in a dose-proportional manner; concentrations in the low-dose group were below the lower limit of quantitation (LLOQ), while Cmax values ranging from 0.467 ng/mL (mid-dose, females) to 15.3 ng/mL (high dose, females), and AUC0-last values from 2.18 h·ng/mL (mid-dose, females) to 61.5 h·ng/mL (high dose, females). Accumulation factors ranged from 0.135 to 1.66, indicating no significant drug accumulation. Developmental parameters and histopathological examinations of respiratory tissues revealed no treatment-related abnormalities. The NOAEL was determined to be 1202.4 ± 176.4 μg/kg, the highest dose tested. Inhaled PEG IFNα-2b demonstrated a favorable safety and TK profile in juvenile rats at doses up to 1202.4 ± 176.4 μg/kg, supporting its potential as an inhaled antiviral therapy for pediatric respiratory infections.
Keywords: Pegylated interferon α-2b, Inhalation toxicology, juvenile animal study, toxicokinetics, NOAEL
Received: 20 Aug 2025; Accepted: 28 Nov 2025.
Copyright: © 2025 Ji, Ji, Li and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Qinfang Wang
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