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Abstract

Pulmonary fate of [3H]bleomycin A2 in mice.

J S Lazo and E T Pham
Journal of Pharmacology and Experimental Therapeutics January 1984, 228 (1) 13-18;
J S Lazo
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Abstract

The pulmonary fate of radiolabeled bleomycin [S-methyl-3H]bleomycin A2 ( [3H]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 [3H]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 [3H]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 [3H]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.

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Journal of Pharmacology and Experimental Therapeutics
Vol. 228, Issue 1
1 Jan 1984
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Abstract

Pulmonary fate of [3H]bleomycin A2 in mice.

J S Lazo and E T Pham
Journal of Pharmacology and Experimental Therapeutics January 1, 1984, 228 (1) 13-18;

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Abstract

Pulmonary fate of [3H]bleomycin A2 in mice.

J S Lazo and E T Pham
Journal of Pharmacology and Experimental Therapeutics January 1, 1984, 228 (1) 13-18;
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