Comparison of Single-Dose Toxicity by Intravenous Infusion or Bolus Injection with CKD-602, a Camptothecin Anticancer Agent in Rats (I): Toxic Effects with regard to Mortality and Clinical Signs

• Published in: Journal of toxicology and public health Vol. 20; no. 4; pp. 375 - 380
• Main Authors: Kim, Choong-Yong, Han, Junghee, Yang, Byung-Chul, Kim, Joon-Kyum, Kim, Jong-Choon, Ha, Chang-Su, Han, Sang-Seop
• Format: Journal Article
• Language: Korean
• Published: 2004
• Subjects: Infusion; Rat; Toxicity; CKD-602; Bolus; Anticancer
• ISSN: 1226-8399

The toxicity of CKD-602 was investigated at doses of 0, 3, 9, and 27 mg/kg in rats, by administering the same total dose over 24-hr continuous infusion or bolus injection. CKD-602 treatment caused gastrointestinal symptoms such as diarrhea, soft stool, and soiled perineal region. It also decreased body weight at doses of 9 and 27 mg/kg in a dose-dependant manner. At 3 mg/ kg, clinical signs and body weight decrease were more severe in the infusion group than in the bolus group. In the bolus group, mortalities were 0/8, 0/8, 1/8, and 3/8 at 0, 3, 9, and 27 mg/kg, respectively, whereas those were 0/8, 1/8, 8/8, and 8/8 in the infusion group. $LD_{50}$ values were 36.25 mg/kg for bolus and 3.50 mg/kg for infusion, respectively. This finding indicates that the toxic potency of CKD-602 by continuous infusion is about 10 times higher than by bolus injection. Our findings suggest that the toxic effects of CKD-602 are dependant upon the duration of intravenous administration.