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Irinotecan

Current Clinical Status and Pharmacological Aspects

  • Chapter
Camptothecins in Cancer Therapy

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

Abstract

Irinotecan (Fig. 1), also known as CPT-11, is a semisynthetic derivative of 20(S)camptothecin (1), a pentacyclic alkaloid first identified in extracts of the Chinese shrub Camptotheca acuminata. The mechanism of action of camptothecin has been covered in other chapters of this book and need not be revisited here. However, it is pertinent to point out that CPT-11 itself is only a very weak stabilizer of the cleavable complex formed between DNA and topoisomerase I (TOP-I) and requires conversion to an active metabolite, SN-38 (2). The latter is one of the most potent TOP-I poisons known, which may be a result of the prolonged half-life of interaction with the cleavable complex (3). In vivo, the activation of CPT-11 to SN-38 is carried out by carboxylesterases (4–8). In turn, SN-38 can be conjugated to SN-38 β-glucuronide (9,10). CPT-11 is also metabolized to an aminopentanocarboxylic (APC), metabolite (see Fig. 1), and other minor, mostly inactive, products by cytochrome P450 3A4/5 (11–14).

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  1. Preclinical Development Team, Johnson and Johnson Research Pty. Ltd., Eveleigh, NSW, Australia

    Laurent P. Rivory PhD

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  1. Department of Pharmacy Practice and Science, College of Pharmacy, University of Kentucky, Lexington, KY

    Val R. Adams PharmD

  2. Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY

    Thomas G. Burke PhD

  3. Experimental Therapeutics Program, Lucille P. Markey Cancer Center, University of Kentucky Medical Center, University of Kentucky, Lexington, KY

    Thomas G. Burke PhD

  4. Tigen Pharmaceuticals Inc., Lexington, KY

    Thomas G. Burke PhD

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Rivory, L.P. (2005). Irinotecan. In: Adams, V.R., Burke, T.G. (eds) Camptothecins in Cancer Therapy. Cancer Drug Discovery and Development. Humana Press. https://doi.org/10.1385/1-59259-866-8:229

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