Toxicity study of a new camptothecin anti-cancer agent CKD-602 in dogs: 4-week continuous intravenous dose by infusion pump and 4-week repeated intravenous dose.
In evaluating toxicity, one of the most important factors is the administration method, because it can affect the exposure and absorbance level of the test article, and, consequently, influence the interpretation of toxicity test results. Continuous intravenous (IV) administration is a widely used administration method for anti-cancer drugs in clinical settings. Previous studies have reported the toxic effects of the test article following repeated IV dosing of CKD-602, a novel camptothecin-derivative anti-tumor agent that was developed by Chong Kun Dang Pharmaceutical Corporation in Seoul, Korea. However, CKD-602-related toxicities induced by IV infusion administration have not yet been evaluated, although the drug is more widely used in clinical settings. In the present study, CKD-602 was administered using a continuous IV infusion pump and using repeated IV administration at doses of 0, 0.003, or 0.01 mg/kg/day for 4 weeks to compare and evaluate the drug-induced toxicities using the two different administration methods. Higher mortality, more severe clinical symptoms, increased complete blood count, serum biochemistry, and histopathology were demonstrated when CKD-602 was administered using the 4-week continuous IV infusion pump method compared with the repeated IV administration method. Based on these results, we conclude that the administration of CKD-602 using the 4-week continuous IV infusion pump method can elicit more severe toxicity than that using 4-week repeated IV dosing method. Thus, more attention should be paid to the administration of CKD-602 using continuous IV infusion in the clinical setting.
Han
S C
SC
Korea Institute of Toxicology, Daejeon, South Korea.
Kim
D G
DG
Han
E H
EH
Kim
Y B
YB
Hwang
I C
IC
Kim
C Y
CY
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000633:toxicity*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008297:Male; D012720:Severity of Illness Index
D000972:Antineoplastic Agents, Phytogenic; C116963:belotecan; D002166:Camptothecin