Pharmacokinetics and tissue distribution of interferon α2b (Pseudomonas putida) administered via atomization inhalation and intramuscular injection by ¹²⁵I labeling

Objective: To compare the in vivo pharmacokinetics and tissue distribution difference of interferon α2b(IFNα2b, Pseudomonas putida) in rabbits administered via atomization inhalation and intramuscular injection. Methods: IFNα2b was radiolabeled with iodine-125 and then administered to rabbits at a dose of 450000 IU/kg body weight (according to the recommended dosage for humans of 150000 IU/kg body weight) via atomization inhalation and intramuscular injection. The pharmacokinetics of IFNα2b in rabbits was studied using radioisotope tracer technique. The distribution of IFNα2b in different tissues and the different parts of the lung at 0.5, 2, 4, 8, and 12 h was detected by ex vivo imaging and γ-counting methods. Results: The pharmacokinetic results showed that the area under the curve, mean retention time, clearance, and half-life time of intramuscular injection group were(39.20 ± 1.89)ng·h^-1·ml^-1, (6.90±0.21)h, (0.09 ± 0.004)ml·kg^-1·h^-1, and (7.30 ± 0.38)h, respectively, and the corresponding data of atomization inhalation group were (45.10 ± 4.65)ng·h^-1·ml^-1, (16.10 ± 1.37)h, (0.06 ± 0.010)ml·kg^-1·h^-1, and (12.10 ± 1.19)h, respectively. The tissue distribution results indicated that the IFNα2b administered via atomization inhalation was mainly distributed in the lung, with the detectable radioactive signal as long as 12 h. However, high radioactive signals were observed in the kidney in the intramuscular injection group at 2 h, and then the signals gradually diminished. Conclusions: Compared with the conventional intramuscular injection, atomization inhalation could evidently prolong the in vivo residence time of IFNα2b and exhibited higher lung accumulation. Consequently, the atomization inhalation of IFNα2b may have better therapeutic effect and longer duration of drug action for pulmonary viral and respiratory tract infections. (authors)