Enhanced Anticancer Effect but Low Hepatotoxicity of Clotrimazole Solid Suppository with Poloxamer188 and Propylene Glycol in Mouse Tumor Model

• Published in: The FASEB journal 2006-03, Vol.20 (5), p.A1130-A1130
• Main Authors: Lee, Yoon‐Seok, Paek, Seung‐Hwan, Choi, Han‐Gon, Yong, Chul Soon, Kim, Jung‐Ae
• Format: Article
• Language: English
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fasebj.20.5.A1130-a

Clotrimazole, an antifungal imidazole derivative, has been shown to inhibit the proliferation of normal and cancer cells in vitro and tumor growth in vivo. Also, it is known as a potent inhibitor of angiogenesis. However, clinical application of clotrimazole has shown hepatotoxicity possibly associated with the imidazole moiety. The present study assessed the anticancer efficacy and side effects of clotrimazole rectal suppository administration by comparing with oral route. The rectal suppository was made with 70% poloxamer 188 (P188) and 30% propylene glycol (PG), which was a solid phase at room temperature and instantly melted at physiological temperature. The two types of syngenic mouse tumor model (rectal and skin tumor) were generated. Clotrimazole treatment, which started after the tumor has developed, decreased the tumor size in the route of both oral and rectal suppository administration. However, the decrease in the tumor size and the survival rate of the mice were significantly higher in the group treated with rectal suppository than in the group treated with oral administration. In addition, the hepatotoxicity assessed as the activity of glutamate oxaloacetate transaminase and hepatic lipid peroxidation was significantly higher in the mice treated with clotrimazole through oral route than rectal suppository.