Pharmacokinetics and toxicity of inhaled human interferon-alpha in patients with lung cancer.
Eight patients with advanced, previously treated non-small cell lung cancer inhaled natural leukocyte interferon-alpha (IFN-alpha) from a dosimeter-equipped jet nebulizer. Single doses of IFN ranged from 1 x 10(6) to 120 x 10(6) IU. Serum IFN was undetectable after single doses of 1 x 10(6) to 18 x 10(6) IU, but 60 x 10(6) IU resulted in measurable levels of circulating IFN in 3 out of 6 patients. All 5 patients who inhaled 120 x 10(6) IU had between 11 and 35 IU of IFN per milliliter of serum for at least 12 h. No systemic or local side effects were observed after 1 x 10(6) to 18 x 10(6) IU, but doses of 60 x 10(6) to 120 x 10(6) IU resulted in temperature rise, headache, and malaise. All symptoms started within 3-6 h, reached their peak by 8-10 h, and lasted until 12-24 h after inhalation. A decrease (greater than 20%) in peak expiratory flow following inhalation was temporarily found in 2 patients. We conclude that IFN, given by inhalation, penetrates into the blood stream, thus causing systemic side effects similar to those described after systemic IFN administration and, in addition, occasionally reversible airflow obstruction.
Kinnula
V
V
Department of Pulmonary Medicine, Helsinki University Central Hospital, Finland.
Mattson
K
K
Cantell
K
K
D000280:Administration, Inhalation; D000368:Aged; D001831:Body Temperature / Q000187:drug effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000628:therapy*; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D007370:Interferon Type I / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D008175:Lung Neoplasms / Q000378:metabolism / Q000628:therapy*; D008297:Male; D008875:Middle Aged
D007370:Interferon Type I