Irinotecan is a semi-synthetic analogue of camptothecin which is a topoisomerase IB inhibitor. It is used to treat colorectal cancer. It's mechanism of action against topoisomerase I is that it forms a tertiary complex between the DNA and the topoisomerase I enzyme causing double strand breaks. It first has to be metabolized by liver carboxylesterase 1 into SN-38, which is the active metabolite that inhibits topoisomerase. SN-38 can be inactivated by UGT1A1 into SN-38 glucuronide which upregulated in some individuals leading to irinotecan resistance. Individuals might also have a reduced function variant of UGT1A1 which can lead to increased metabolism of irinotecan and leads to irinotecan toxicity. Toxicity of irinotecan leads to gastrointestinal complications as well as nausea, vomiting and headaches. Irinotecan is administered usually intravenously as a solution.

Irinotecan Topoisomerase Inhibitor Pathway References