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Abstract

QUANTIFICATION OF IRINOTECAN (CPT-11) AND ITS METABOLITE, SN-38, IN RAT PLASMA AND BILE SAMPLES: APPLICATION TO PHARMACOKINETIC STUDIES

Ranjan Kumar Singh* and Narsingh Rajpoot

ABSTRACT

Mechanism of Action: Irinotecan is a semisynthetic, water-soluble derivative of camptothecin, which is a cytotoxic alkaloid extracted from plants such as Camptotheca acuminata.[3] Irinotecan and its active metabolite, SN-38, inhibit the action of topoisomerase I, an enzyme that produces reversible single-strand breaks in DNA during DNA replication. These single-strand breaks relieve torsional strain and allow DNA replication to proceed. Irinotecan and SN-38 bind to the topoisomerase I-DNA complex and prevent religation of the DNA strand, resulting in double-strand DNA breakage and cell death. The precise contribution of SN-38 to the activity of irinotecan in humans is not known.[4] Irinotecan is cell cycle phasespecific (S-phase).[5]

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