The safety, tolerability, pharmacokinetics, and pharmacodynamics of nebulized pegylated interferon α-2b in healthy adults: a randomized phase 1 trial
Abstract Background Interferons (IFNs) are proteins that combat viruses and regulate the immune system. Studies have demonstrated that aerosol inhalation of IFNα is both effective and safe for treating respiratory infections. However, IFNα has a short half-life and is rapidly cleared by lung defense...
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BMC
2025-05-01
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| Series: | BMC Pharmacology and Toxicology |
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| Online Access: | https://doi.org/10.1186/s40360-025-00937-9 |
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| author | Wenqi Huang Yanneng Kang Yajun Zhao Jiao Yang Changjuan Dai Weibing Wu Jinchao Xu Wen Jin Xiaolu Wu Qing Zhou |
| author_facet | Wenqi Huang Yanneng Kang Yajun Zhao Jiao Yang Changjuan Dai Weibing Wu Jinchao Xu Wen Jin Xiaolu Wu Qing Zhou |
| author_sort | Wenqi Huang |
| collection | DOAJ |
| description | Abstract Background Interferons (IFNs) are proteins that combat viruses and regulate the immune system. Studies have demonstrated that aerosol inhalation of IFNα is both effective and safe for treating respiratory infections. However, IFNα has a short half-life and is rapidly cleared by lung defenses. Polyethylene glycol (PEG) ylation is a common strategy to extend the duration of drug action. PegIFNα-2b is a long-acting interferon formed by the covalent binding of 40 kDa Y-shaped branched PEG with recombinant human IFNα-2b. This study aimed to assess the safety, tolerability, pharmacokinetic, and pharmacodynamic characteristics of nebulized PegIFNα-2b in healthy adult subjects, providing guidance for further clinical investigations. Methods This study employed a randomized, controlled clinical trial design with a total of 18 healthy adult subjects enrolled. Participants were randomly assigned in a 1:1:1 ratio to three groups. Treatment group 1 and group 2 received 90 µg and 180 µg of nebulized PegIFNα-2b, respectively, while the control group was administered a combination of 180 µg PegIFNα-2b and 15 mg inhalable Ambroxol Hydrochloride solution, all in a single dose. Safety, tolerability, and blood drug concentration were assessed, along with blood neopterin levels for pharmacokinetic and pharmacodynamic evaluation. Results The incidence of adverse events (AEs) was 38.9% (7/18) with no significant difference among the groups (P > 0.05). AEs included anemia (N = 5) and leukopenia (N = 2), predominantly of grade 1 severity (6/7), with no severe events. Blood PegIFNα-2b concentrations were below detection limits in most subjects, except one in treatment group 2. Neopterin levels were generally low in treatment group 1 and the control group, with slightly higher observed in most subjects of treatment group 2, but differences were not significant (P > 0.05). Conclusions Nebulized PegIFNα-2b at doses of 90 µg and 180 µg showed acceptable safety and tolerability. Minimal systemic absorption was observed following inhalation. Further studies are needed to explore its potential, especially in patients with lower respiratory tract infections. Clinical trial registration ChiCTR2300074909, retrospectively registered in https://www.chictr.org.cn/ at 20 August 2023. |
| format | Article |
| id | doaj-art-91f8ad7c2a2d48228b3bdf5e8b274c95 |
| institution | Kabale University |
| issn | 2050-6511 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMC |
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| series | BMC Pharmacology and Toxicology |
| spelling | doaj-art-91f8ad7c2a2d48228b3bdf5e8b274c952025-08-20T03:53:57ZengBMCBMC Pharmacology and Toxicology2050-65112025-05-0126111110.1186/s40360-025-00937-9The safety, tolerability, pharmacokinetics, and pharmacodynamics of nebulized pegylated interferon α-2b in healthy adults: a randomized phase 1 trialWenqi Huang0Yanneng Kang1Yajun Zhao2Jiao Yang3Changjuan Dai4Weibing Wu5Jinchao Xu6Wen Jin7Xiaolu Wu8Qing Zhou9Department of Hepatology, Xiamen Humanity Hospital Fujian Medical UniversityDepartment of Hepatology, Xiamen Humanity Hospital Fujian Medical UniversityDepartment of Hepatology, Xiamen Humanity Hospital Fujian Medical UniversityDepartment of Hepatology, Xiamen Humanity Hospital Fujian Medical UniversityDepartment of Hepatology, Xiamen Humanity Hospital Fujian Medical UniversityDepartment of Hepatology, Xiamen Humanity Hospital Fujian Medical UniversityDepartment of Hepatology, Xiamen Humanity Hospital Fujian Medical UniversityDepartment of Hepatology, Xiamen Humanity Hospital Fujian Medical UniversityDepartment of Hepatology, Xiamen Humanity Hospital Fujian Medical UniversityDepartment of Hepatology, Xiamen Humanity Hospital Fujian Medical UniversityAbstract Background Interferons (IFNs) are proteins that combat viruses and regulate the immune system. Studies have demonstrated that aerosol inhalation of IFNα is both effective and safe for treating respiratory infections. However, IFNα has a short half-life and is rapidly cleared by lung defenses. Polyethylene glycol (PEG) ylation is a common strategy to extend the duration of drug action. PegIFNα-2b is a long-acting interferon formed by the covalent binding of 40 kDa Y-shaped branched PEG with recombinant human IFNα-2b. This study aimed to assess the safety, tolerability, pharmacokinetic, and pharmacodynamic characteristics of nebulized PegIFNα-2b in healthy adult subjects, providing guidance for further clinical investigations. Methods This study employed a randomized, controlled clinical trial design with a total of 18 healthy adult subjects enrolled. Participants were randomly assigned in a 1:1:1 ratio to three groups. Treatment group 1 and group 2 received 90 µg and 180 µg of nebulized PegIFNα-2b, respectively, while the control group was administered a combination of 180 µg PegIFNα-2b and 15 mg inhalable Ambroxol Hydrochloride solution, all in a single dose. Safety, tolerability, and blood drug concentration were assessed, along with blood neopterin levels for pharmacokinetic and pharmacodynamic evaluation. Results The incidence of adverse events (AEs) was 38.9% (7/18) with no significant difference among the groups (P > 0.05). AEs included anemia (N = 5) and leukopenia (N = 2), predominantly of grade 1 severity (6/7), with no severe events. Blood PegIFNα-2b concentrations were below detection limits in most subjects, except one in treatment group 2. Neopterin levels were generally low in treatment group 1 and the control group, with slightly higher observed in most subjects of treatment group 2, but differences were not significant (P > 0.05). Conclusions Nebulized PegIFNα-2b at doses of 90 µg and 180 µg showed acceptable safety and tolerability. Minimal systemic absorption was observed following inhalation. Further studies are needed to explore its potential, especially in patients with lower respiratory tract infections. Clinical trial registration ChiCTR2300074909, retrospectively registered in https://www.chictr.org.cn/ at 20 August 2023.https://doi.org/10.1186/s40360-025-00937-9Pegylated interferon α-2bNebulizationSafetyPharmacodynamics |
| spellingShingle | Wenqi Huang Yanneng Kang Yajun Zhao Jiao Yang Changjuan Dai Weibing Wu Jinchao Xu Wen Jin Xiaolu Wu Qing Zhou The safety, tolerability, pharmacokinetics, and pharmacodynamics of nebulized pegylated interferon α-2b in healthy adults: a randomized phase 1 trial BMC Pharmacology and Toxicology Pegylated interferon α-2b Nebulization Safety Pharmacodynamics |
| title | The safety, tolerability, pharmacokinetics, and pharmacodynamics of nebulized pegylated interferon α-2b in healthy adults: a randomized phase 1 trial |
| title_full | The safety, tolerability, pharmacokinetics, and pharmacodynamics of nebulized pegylated interferon α-2b in healthy adults: a randomized phase 1 trial |
| title_fullStr | The safety, tolerability, pharmacokinetics, and pharmacodynamics of nebulized pegylated interferon α-2b in healthy adults: a randomized phase 1 trial |
| title_full_unstemmed | The safety, tolerability, pharmacokinetics, and pharmacodynamics of nebulized pegylated interferon α-2b in healthy adults: a randomized phase 1 trial |
| title_short | The safety, tolerability, pharmacokinetics, and pharmacodynamics of nebulized pegylated interferon α-2b in healthy adults: a randomized phase 1 trial |
| title_sort | safety tolerability pharmacokinetics and pharmacodynamics of nebulized pegylated interferon α 2b in healthy adults a randomized phase 1 trial |
| topic | Pegylated interferon α-2b Nebulization Safety Pharmacodynamics |
| url | https://doi.org/10.1186/s40360-025-00937-9 |
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