4-Week repeated intravenous dose toxicity study of a new camptothecin anticancer agent CKD-602 in dogs

Kim, J C; Shin, Dong–Ho; Park, S H; Park, S C; Kim, Y B; Kim, Hyoung-Chin; Ra, S W; Cho, K H; Kang, Boo-Hyon; Chung, Moon-Koo

doi:10.1016/j.fct.2004.12.020

Cited by 4 publications

(2 citation statements)

References 22 publications

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“…Studies have been performed in embryonic and adult rats, 173–175 dogs, 176 pregnant does and rabbits 177 as well as human subjects with small cell lung cancer. 178 In general, daily doses of 0.01 mg/kg were well tolerated in both maternal and embryonic subjects depending on the length of administration.…”

Section: Camptothecin Modificationsmentioning

confidence: 99%

“…Significant efforts have focused on the acute toxicity of belotecan in a variety of tumor free animals. Studies have been performed in embryonic and adult rats, − dogs, pregnant does and rabbits and human subjects with small-cell lung cancer . In general, daily doses of 0.01 mg/kg were well tolerated in both maternal and embryonic subjects depending on the length of administration.…”

Section: Camptothecin Modificationsmentioning

confidence: 99%

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Cancer Therapies Utilizing the Camptothecins: A Review of the in Vivo Literature

2010

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This review summarizes the in vivo assessment--preliminary, preclinical, and clinical--of chemotherapeutics derived from camptothecin or a derivative. Camptothecin is a naturally occurring, pentacyclic quinoline alkaloid that possesses high cytotoxic activity in a variety of cell lines. Major limitations of the drug, including poor solubility and inactivity at physiological conditions, prevent full clinical utilization. Camptothecin remains at equilibrium in an active lactone form and inactive hydrolyzed carboxylate form. The active lactone binds to DNA topoisomerase I cleavage complex, believed to be the single site of activity inhibiting DNA religation, resulting in apoptosis. A series of small molecule camptothecin derivatives have been developed that increase solubility, lactone stability and bioavailability to varying levels of success. A number of macromolecular agents have also been described wherein camptothecin(s) are covalently appended or non-covalently associated with the goal of improving solubility and lactone stability, while taking advantage of the tumor physiology to deliver larger doses of drug to the tumor with lower systemic toxicity. With the increasing interest in drug delivery and polymer therapeutics, additional constructs are anticipated. The goal of this review is to summarize the relevant literature for others interested in the field of camptothecin-based therapeutics, specifically in the context of biodistribution, dosing regimens, and pharmacokinetics with the desire of providing a useful source of comparative data. To this end, only constructs where in vivo data is available are reported. The review includes published reports in English through mid-2009.

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