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Title: Pulmonary fate of (/sup 3/H)bleomycin A2 in mice

Abstract

The pulmonary fate of radiolabeled bleomycin (S-methyl-/sup 3/H)bleomycin A2 ((/sup 3/H)BLM A2) was studied in mice after intratracheal (i.t.) or s.c. injection. The loss of radioactivity from the lungs followed apparent first-order kinetics during the first 3 hr after i.t. drug instillation with a half-time of removal of 32 min. In addition, the initial pulmonary removal was linear with instilled doses ranging from 0.02 to 2.2 mg/kg. Radioactivity was detected in liver, kidneys, spleen and serum 1 hr after i.t. administration. Approximately 1% of the i.t. administered dose was detected in the lungs after 24 hr, indicating that the rate of removal of radioactivity slowed between 3 and 24 hr after i.t. drug instillation. Eighty percent of the radioactivity found in the lungs 1 hr after i.t. instillation was unmetabolized (/sup 3/H)BLM A2, but by 24 hr less than 25% was unmetabolized drug and almost 40% was the nonfibrogenic metabolite, desamidobleomycin A2. After s.c. administration of 10 mg/kg of (/sup 3/H)BLM A2, peak pulmonary levels were observed between 45 and 60 min and were less than 1% of the injected dose. Pulmonary levels comparable to those seen with a single fibrogenic i.t. dose (2.2 mg/kg) could not be obtained aftermore » a s.c. injection even with a toxic dose of the drug (100 mg/kg). In addition, twice weekly s.c. injections of unlabeled BLM A2 (10 mg/kg) for 5 weeks did not alter the amount of radioactivity seen in the lungs after a s.c. injection of (/sup 3/H)BLM A2. Thus, the pulmonary fibrosis seen with i.t. BLM administration may reflect the high initial content of unmetabolized drug achieved in the lungs.« less

Authors:
;
Publication Date:
Research Org.:
Yale Univ., School of Medicine, New Haven, CT
OSTI Identifier:
6728593
Resource Type:
Journal Article
Journal Name:
J. Pharmacol. Exp. Ther.; (United States)
Additional Journal Information:
Journal Volume: 228:1
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; BLEOMYCIN; TISSUE DISTRIBUTION; BLOOD SERUM; FIBROSIS; KIDNEYS; LIVER; LUNGS; MICE; SPLEEN; TRACER TECHNIQUES; TRITIUM COMPOUNDS; ANIMALS; ANTI-INFECTIVE AGENTS; ANTIBIOTICS; ANTIMITOTIC DRUGS; ANTINEOPLASTIC DRUGS; BODY; DIGESTIVE SYSTEM; DISTRIBUTION; DRUGS; GLANDS; ISOTOPE APPLICATIONS; LABELLED COMPOUNDS; MAMMALS; ORGANS; PATHOLOGICAL CHANGES; RESPIRATORY SYSTEM; RODENTS; VERTEBRATES; 550501* - Metabolism- Tracer Techniques

Citation Formats

Lazo, J S, and Pham, E T. Pulmonary fate of (/sup 3/H)bleomycin A2 in mice. United States: N. p., 1984. Web.
Lazo, J S, & Pham, E T. Pulmonary fate of (/sup 3/H)bleomycin A2 in mice. United States.
Lazo, J S, and Pham, E T. Sun . "Pulmonary fate of (/sup 3/H)bleomycin A2 in mice". United States.
@article{osti_6728593,
title = {Pulmonary fate of (/sup 3/H)bleomycin A2 in mice},
author = {Lazo, J S and Pham, E T},
abstractNote = {The pulmonary fate of radiolabeled bleomycin (S-methyl-/sup 3/H)bleomycin A2 ((/sup 3/H)BLM A2) was studied in mice after intratracheal (i.t.) or s.c. injection. The loss of radioactivity from the lungs followed apparent first-order kinetics during the first 3 hr after i.t. drug instillation with a half-time of removal of 32 min. In addition, the initial pulmonary removal was linear with instilled doses ranging from 0.02 to 2.2 mg/kg. Radioactivity was detected in liver, kidneys, spleen and serum 1 hr after i.t. administration. Approximately 1% of the i.t. administered dose was detected in the lungs after 24 hr, indicating that the rate of removal of radioactivity slowed between 3 and 24 hr after i.t. drug instillation. Eighty percent of the radioactivity found in the lungs 1 hr after i.t. instillation was unmetabolized (/sup 3/H)BLM A2, but by 24 hr less than 25% was unmetabolized drug and almost 40% was the nonfibrogenic metabolite, desamidobleomycin A2. After s.c. administration of 10 mg/kg of (/sup 3/H)BLM A2, peak pulmonary levels were observed between 45 and 60 min and were less than 1% of the injected dose. Pulmonary levels comparable to those seen with a single fibrogenic i.t. dose (2.2 mg/kg) could not be obtained after a s.c. injection even with a toxic dose of the drug (100 mg/kg). In addition, twice weekly s.c. injections of unlabeled BLM A2 (10 mg/kg) for 5 weeks did not alter the amount of radioactivity seen in the lungs after a s.c. injection of (/sup 3/H)BLM A2. Thus, the pulmonary fibrosis seen with i.t. BLM administration may reflect the high initial content of unmetabolized drug achieved in the lungs.},
doi = {},
url = {https://www.osti.gov/biblio/6728593}, journal = {J. Pharmacol. Exp. Ther.; (United States)},
number = ,
volume = 228:1,
place = {United States},
year = {1984},
month = {1}
}