Accession Number:

ADA550744

Title:

Four Week Oral Dose Range-Finding Study of WR242511 in Dogs

Descriptive Note:

Corporate Author:

ILLINOIS UNIV AT CHICAGO CIRCLE DEPT OF PHARMACOLOGY

Personal Author(s):

Report Date:

1994-03-09

Pagination or Media Count:

114.0

Abstract:

This study evaluated the toxicity of WR242511 tartrate in dogs following four weeks of daily administration by gelatin capsule. The primary toxic effects of WR242511 tartrate were seen in the RBCs, liver and the lung. Anemia and methemoglobinemia were observed in all the dose levels tested. Compensatory changes to the anemic state included macrocytosis, reticulocytosis and increased nucleated RBCs. Decreases in body weight and food consumption were seen at the high dose level and possibly the mid dose level. Microscopic lesions were seen in the liver and the lung at all dose levels tested. Hepatocellular swelling was supported by decreases in the AG ratio and increases in haptoglobin levels in mid andor high dose animals. Pulmonary lesions alveolar proteinic exudates, macrophage infiltration and acute alveolar inflammation and mild to moderate thrombocytopenia were seen at all dose levels. Leukocytosis consisting of increased mature neutrophils, possibly secondary to stress, was seen in high animals and possibly in the mid dose female. On the basis of the findings from this study and after consultation with the Sponsor, the following three dose levels have been selected for use in the four week oral toxicity study 0.1, 0.3 and 1.0 mg basekgday.

Subject Categories:

  • Biology
  • Anatomy and Physiology
  • Toxicology

Distribution Statement:

APPROVED FOR PUBLIC RELEASE