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

Journal Article · Sun Jan 01 04:00:00 EST 1984 · J. Pharmacol. Exp. Ther.; (United States)

OSTI ID:6728593

Lazo, J S; Pham, E T

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.

• Research Organization: Yale Univ., School of Medicine, New Haven, CT
• OSTI ID: 6728593
• Journal Information: J. Pharmacol. Exp. Ther.; (United States), Journal Name: J. Pharmacol. Exp. Ther.; (United States) Vol. 228:1; ISSN JPETA
• Country of Publication: United States
• Language: English

Related Subjects

550501* -- Metabolism-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMALS
ANTI-INFECTIVE AGENTS
ANTIBIOTICS
ANTIMITOTIC DRUGS
ANTINEOPLASTIC DRUGS
BLEOMYCIN
BLOOD SERUM
BODY
DIGESTIVE SYSTEM
DISTRIBUTION
DRUGS
FIBROSIS
GLANDS
ISOTOPE APPLICATIONS
KIDNEYS
LABELLED COMPOUNDS
LIVER
LUNGS
MAMMALS
MICE
ORGANS
PATHOLOGICAL CHANGES
RESPIRATORY SYSTEM
RODENTS
SPLEEN
TISSUE DISTRIBUTION
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES