9-nitrocamptothecin liposome aerosol: lack of subacute toxicity in dogs.
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.
Department of Molecular Virology and Microbiology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA. bgilbert@bcm.tmc.edu
Brian E
BE
Gilbert
Alexander
A
Seryshev
Vernon
V
Knight
Cory
C
Brayton
D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D001774:Blood Chemical Analysis; D001835:Body Weight / Q000187:drug effects; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000633:toxicity*; D004285:Dogs; D005260:Female; D008081:Liposomes; D008297:Male; D009330:Nebulizers and Vaporizers; D009929:Organ Size; D018675:Toxicity Tests; D016482:Urinalysis
D000336:Aerosols; D000970:Antineoplastic Agents; D008081:Liposomes; C079905:rubitecan; D002166:Camptothecin