9-nitrocamptothecin liposome aerosol: lack of subacute toxicity in dogs

Inhal Toxicol. 2002 Feb;14(2):185-97. doi: 10.1080/089583701753403980.

Abstract

9-Nitrocamptothecin (9-NC) dilauroylphosphatidylcholine (DLPC) liposome aerosol was evaluated for potential toxicity in an 8-wk, subacute toxicity study in dogs. Fourteen adult dogs were divided into 2 groups with 10 animals in the 9-NC-DLPC treatment group and 4 animals in the DLPC-only vehicle control group. 9-NC-DLPC was administered to the animals using an Aerotech II nebulizer flowing at 10 L/min. Full-face exposures for 60 min were conducted for 5 consecutive days a week for 8 wk. The estimated deposited aerosol dose was 24.7 microg/kg/day. Animals in the vehicle control group received aerosolized DLPC only. Body weight, food consumption, urinalysis, in-life observations, hematology, plasma chemistry, and necropsy and histopathology were monitored before and during the treatment period and in a subset of animals for 2 wk following the end of treatment. Animals were observed for signs of pharmacologic and/or toxicologic effects three times on days of dosing and once daily on nondosing days. 9-NC-DLPC liposomes administered as a small-particle aerosol were determined to be nontoxic to dogs when given for 5 days/wk, for a duration of 8 wk. DLPC-only liposome also had no toxic effects.

MeSH terms

  • Administration, Inhalation
  • Aerosols
  • Animals
  • Antineoplastic Agents / toxicity*
  • Blood Chemical Analysis
  • Body Weight / drug effects
  • Camptothecin / analogs & derivatives*
  • Camptothecin / toxicity*
  • Dogs
  • Female
  • Liposomes
  • Male
  • Nebulizers and Vaporizers
  • Organ Size
  • Toxicity Tests
  • Urinalysis

Substances

  • Aerosols
  • Antineoplastic Agents
  • Liposomes
  • rubitecan
  • Camptothecin