Early phase pharmacokinetics and pulmonary disposition of parenteral bleomycin A2 (BLM A2) in BLM sensitive and resistant strains of mice

Conference · Sat Mar 01 04:00:00 EST 1986 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:5456393

Harrison, J H; Filderman, A E; Lazo, J S

Recent studies have shown that C57BL/6N mice are more sensitive than BALB/c mice to the pulmonary fibrotic effects of BLM. To determine whether the two strains show corresponding differences in BLM pharmacokinetics and pulmonary disposition after parenteral injection, the authors treated C57BL/6N and BALB/c mice with a single dose of (/sup 3/H)-BLM (80 mg/kg,iv). Serial blood samples were collected over 30 min from each animal, followed by pulmonary lavage and collection organs. In C57 BL/6N mice, BLM A2 plasma levels were maximal (178-227 ..mu..g/ml) in the first sample (2 min) and declined in a first order manner with a half-life of 12.6 +/- 3.6 (SD) min. The Vd was 232 +/- 29 ml/kg body weight. Pulmonary lavage recovered 68.1 +/- 3.5% of total lung radioactivity. BLM A2 was the predominant radioactive species and was present in equal proportions in lavage fluid and lung tissue. BALB/c mice showed similar BLM A2 distribution and elimination, and the recovery of BLM A2 in lavage fluid was not decreased as compared with C57BL/6N mice. Therefore, the resistance of BALB/c mice to BLM pulmonary toxicity does not appear to result from enhanced elimination of the drug or relative exclusion of BLM from lung tissues at this dose. These findings indicate that after iv injection, BLM rapidly distributes through a volume similar to extracellular water and, of particular interest, the majority of lung BLM is accessible to pulmonary lavage.

• Research Organization: Yale Univ., New Haven, CT
• OSTI ID: 5456393
• Report Number(s): CONF-8604222-
• Conference Information: Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Journal Volume: 45:3
• Country of Publication: United States
• Language: English

Related Subjects

550201 -- Biochemistry-- Tracer Techniques
560305* -- Chemicals Metabolism & Toxicology-- Vertebrates-- (-1987)
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
ANTI-INFECTIVE AGENTS
ANTIBIOTICS
ANTIMITOTIC DRUGS
ANTINEOPLASTIC DRUGS
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL HALF-LIFE
BIOLOGICAL MATERIALS
BIOLOGICAL VARIABILITY
BLEOMYCIN
BLOOD
BLOOD PLASMA
BODY
BODY FLUIDS
DRUGS
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
LAVAGE
LUNGS
MAMMALS
MATERIALS
MICE
ORGANS
REACTION KINETICS
RESPIRATORY SYSTEM
RETENTION
RODENTS
SENSITIVITY
TOXICITY
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES