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4-Week repeated intravenous dose toxicity study of a new camptothecin anticancer agent CKD-602 in dogs.
Food Chem Toxicol. 2005 May; 43(5):699-706.FC

Abstract

CKD-602 is a new camptothecin derivative antitumor agent with a formula (7-[2-(N-isopropylamino)ethyl]-(20S)-camptothecin) developed by Chong Kun Dang Pharmaceutical Company in Korea. In the present study, the subacute toxicity of CKD-602 was investigated after 4-week repeated intravenous administration of the test chemical in beagle dogs. The test chemical was administered intravenously at dose levels of 0, 0.001, 0.005, or 0.01 mg/kg/day for 4 weeks to male and female dogs (n = 3 for male and female dogs for each dose). During the test period, clinical signs, mortality, body weights, food and water consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, gross findings, organ weights and histopathology were examined. In the high dose group, an increase in the incidence of abnormal clinical signs and a decrease in food and water intake and body weight gain were observed in both sexes. Hematological investigations revealed decreased white blood cells (WBC) in both sexes and reduced red blood cells (RBC), hemoglobin and hematocrit in females. Histopathological examinations revealed an increase in the incidence of atrophy of the sternal and femoral marrow and spleen in both sexes and atrophy of the thymus and mesenteric lymph node in males. No treatment-related adverse effects were observed in both sexes of the low and middle dose groups. In conclusion, the 4-week repeated intravenous dose of CKD-602 to beagle dogs caused increases in the clinical signs and histopathological changes, and decreases in the body weight gain, food and water intake, RBC, hemoglobin, hematocrit and WBC at the dose level of 0.01 mg/kg/day. In the present experimental conditions, the target organs were determined to be bone marrow, blood cells, spleen, thymus, and mesenteric lymph node. The no-observed-adverse-effect levels (NOAEL) for males and females were considered to be 0.005 mg/kg/day, respectively.

Authors+Show Affiliations

College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, South Korea. toxkim@chonnam.ac.krNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

15778009

Citation

Kim, J-C, et al. "4-Week Repeated Intravenous Dose Toxicity Study of a New Camptothecin Anticancer Agent CKD-602 in Dogs." Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association, vol. 43, no. 5, 2005, pp. 699-706.
Kim JC, Shin DH, Park SH, et al. 4-Week repeated intravenous dose toxicity study of a new camptothecin anticancer agent CKD-602 in dogs. Food Chem Toxicol. 2005;43(5):699-706.
Kim, J. C., Shin, D. H., Park, S. H., Park, S. C., Kim, Y. B., Kim, H. C., Cha, S. W., Cho, K. H., Kang, B. H., & Chung, M. K. (2005). 4-Week repeated intravenous dose toxicity study of a new camptothecin anticancer agent CKD-602 in dogs. Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association, 43(5), 699-706.
Kim JC, et al. 4-Week Repeated Intravenous Dose Toxicity Study of a New Camptothecin Anticancer Agent CKD-602 in Dogs. Food Chem Toxicol. 2005;43(5):699-706. PubMed PMID: 15778009.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 4-Week repeated intravenous dose toxicity study of a new camptothecin anticancer agent CKD-602 in dogs. AU - Kim,J-C, AU - Shin,D-H, AU - Park,S-H, AU - Park,S-C, AU - Kim,Y-B, AU - Kim,H-C, AU - Cha,S-W, AU - Cho,K-H, AU - Kang,B-H, AU - Chung,M-K, PY - 2004/07/22/received PY - 2004/12/14/revised PY - 2004/12/18/accepted PY - 2005/3/22/pubmed PY - 2005/4/26/medline PY - 2005/3/22/entrez SP - 699 EP - 706 JF - Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association JO - Food Chem Toxicol VL - 43 IS - 5 N2 - CKD-602 is a new camptothecin derivative antitumor agent with a formula (7-[2-(N-isopropylamino)ethyl]-(20S)-camptothecin) developed by Chong Kun Dang Pharmaceutical Company in Korea. In the present study, the subacute toxicity of CKD-602 was investigated after 4-week repeated intravenous administration of the test chemical in beagle dogs. The test chemical was administered intravenously at dose levels of 0, 0.001, 0.005, or 0.01 mg/kg/day for 4 weeks to male and female dogs (n = 3 for male and female dogs for each dose). During the test period, clinical signs, mortality, body weights, food and water consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, gross findings, organ weights and histopathology were examined. In the high dose group, an increase in the incidence of abnormal clinical signs and a decrease in food and water intake and body weight gain were observed in both sexes. Hematological investigations revealed decreased white blood cells (WBC) in both sexes and reduced red blood cells (RBC), hemoglobin and hematocrit in females. Histopathological examinations revealed an increase in the incidence of atrophy of the sternal and femoral marrow and spleen in both sexes and atrophy of the thymus and mesenteric lymph node in males. No treatment-related adverse effects were observed in both sexes of the low and middle dose groups. In conclusion, the 4-week repeated intravenous dose of CKD-602 to beagle dogs caused increases in the clinical signs and histopathological changes, and decreases in the body weight gain, food and water intake, RBC, hemoglobin, hematocrit and WBC at the dose level of 0.01 mg/kg/day. In the present experimental conditions, the target organs were determined to be bone marrow, blood cells, spleen, thymus, and mesenteric lymph node. The no-observed-adverse-effect levels (NOAEL) for males and females were considered to be 0.005 mg/kg/day, respectively. SN - 0278-6915 UR - https://www.unboundmedicine.com/medline/citation/15778009/4_Week_repeated_intravenous_dose_toxicity_study_of_a_new_camptothecin_anticancer_agent_CKD_602_in_dogs_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0278-6915(05)00027-X DB - PRIME DP - Unbound Medicine ER -