健康な参加者および軽度の喘息患者における,吸入型JAK1阻害剤AZD0449

Anna Lundahl¹, Rod Hughes², Joachim Almquist¹

¹Clinical Pharmacology & Quantitative Pharmacology, Clinical Pharmacology & Safety Sciences, R&D, AstraZeneca, Gothenburg, Sweden.

British journal of clinical pharmacology

|August 30, 2025

まとめ

AZD0449,新しいJAK1阻害剤は,喘息患者によって安全に吸入され,肺の保持を示しましたが,有意な抗炎症効果はありませんでした. 喘息に対するJAK1阻害剤のさらなる研究が必要である.

科学分野:

薬理学について
呼吸器医学
免疫学

背景:

吸入用コルチコステロイド (ICS) は標準的な喘息治療である.
JAK1阻害剤は,ICS耐性喘息の潜在的代替手段を提供している.
AZD0449は新しい選択的JAK1阻害剤です.

研究の目的:

吸入および静脈内投与AZD0449の安全性,耐受性,薬理動力学 (PK),および薬理動力学 (PD) を評価する.
健康な参加者と軽度の喘息患者のAZD0449を評価する.

主な方法:

1期ランダム化単盲プラセボ対照試験
AZD0449の単発および多重上昇用量は,吸入およびIVで投与されます.
評価された安全性,耐受性,PK,PD (FeNO),pSTAT6抑制.

主要な成果:

AZD0449は安全で,低用量,投与量に比例する全身露出でよく耐えた.
肺保持の証拠は,1日1回投与の適性を示唆した.
FeNOまたはpSTAT6抑制の有意な減少は観察されなかった.

結論:

吸入されたAZD0449は,肺の保持と良好な安全性およびPKプロファイルを示した.
この研究は,喘息に対する吸入小分子JAK1阻害剤の理解を深めた.
評価された用量ではFeNOまたはSTAT6に対する薬動力学的効果は検出されなかった.

キーワード:

JAK阻害剤喘息について炎症窒素酸化物薬理学

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