A Comprehensive Monograph on the Topoisomerase I Inhibitor Irinotecan

I. Executive Summary and Drug Profile

1.1. Overview of Irinotecan: A Semisynthetic Camptothecin Analog

[Irinotecan is a cornerstone chemotherapeutic agent in modern oncology, particularly in the management of gastrointestinal malignancies. It is classified pharmacologically as a topoisomerase I inhibitor, belonging to the camptothecin class of antineoplastic drugs.][1] Structurally, irinotecan is a semisynthetic, water-soluble derivative of camptothecin, a cytotoxic, quinoline-based alkaloid originally extracted from the Chinese ornamental tree,

Camptotheca acuminata[.][1][ This chemical modification to create a water-soluble analog was a critical step in overcoming the poor solubility and formulation challenges of the parent compound, thereby enabling its clinical development and intravenous administration.][3]

[A fundamental characteristic of irinotecan is its nature as a prodrug. It is pharmacologically inert in its administered form and requires in vivo metabolic activation to exert its cytotoxic effects.][1][ This conversion process, which occurs primarily in the liver and plasma, is central to its entire pharmacokinetic and pharmacodynamic profile. The reliance on metabolic activation introduces significant layers of complexity, including high interindividual variability in drug exposure, a distinct toxicity profile, and a susceptibility to numerous drug-drug interactions and pharmacogenomic influences, all of which are critical considerations in its clinical application.][7]

1.2. Chemical and Physical Properties