Irinotecan (CPT-11) is a water-soluble derivative of camptothecan that inhibits topoisomerase I, a key enzyme for DNA replication and repair.
How do you administer irinotecan?
The recommended dose of irinotecan is 180 mg/m² administered once every 2 weeks as an intravenous infusion over a 30- to 90-minute period, followed by infusion with folinic acid and 5-fluorouracil.
Is irinotecan a prodrug?
Irinotecan, a camptothecin analogue, is a prodrug which requires bioactivation to form the active metabolite SN-38. SN-38 acts as a DNA topoisomerase I poison. Irinotecan has been widely used in the treatment of metastatic colorectal cancer, small cell lung cancer and several other solid tumors.
What is the mechanism action of irinotecan?
Irinotecan inhibits the action of topoisomerase I. Irinotecan prevents religation of the DNA strand by binding to topoisomerase I-DNA complex. The formation of this ternary complex interferes with the moving replication fork, which induces replication arrest and lethal double-stranded breaks in DNA.
How is irinotecan metabolized?
Irinotecan is delivered as a prodrug; the active drug is a potent topoisomerase-1 inhibitor, which causes breaks in double-stranded DNA, ultimately leading to cell death. Irinotecan is metabolized by carboxylesterases to the active 7-ethyl-10-hydroxycamptothecin (SN-38) (Figure 1).
How do you dilute irinotecan?
CAMPTOSAR should be diluted in 5% Dextrose Injection, USP, (preferred) or 0.9% Sodium Chloride Injection, USP, to a final concentration range of 0.12 to 2.8 mg/mL. In most clinical trials, CAMPTOSAR was administered in 250 mL to 500 mL of 5% Dextrose Injection, USP.
Why is atropine given before irinotecan?
Subcutaneous atropine 250mcg immediately prior to irinotecan for the prevention of acute cholinergic syndrome. A further 250mcg subcutaneous dose may be given to relieve cholinergic symptoms if they develop.
How is irinotecan excreted?
Irinotecan is eliminated by the liver via glucuronidation and biliary excretion. SN-38 can be excreted intact, lactone-hydrolyzed and excreted, or glucuronidated. Urine excretion of SN-38 accounts for less than 20% of drug elimination.
Where is irinotecan metabolized?
IRI is metabolized in the liver and converted to SN-38, the active metabolite and Topoisomerase I inhibitor, by carboxylesterases (CES) mediated hydrolysis.
What is irinotecan hydrochloride?
Irinotecan Hydrochloride is the hydrochloride salt of a semisynthetic derivative of camptothecin, a cytotoxic, quinoline -based alkaloid extracted from the Asian tree Camptotheca acuminata. Irinotecan, a prodrug, is converted to a biologically active metabolite 7-ethyl-10-hydroxy-camptothecin ( SN-38)…
What is the difference between irinotecan and camptothecin?
Irinotecan is a semisynthetic derivative of camptothecin, a cytotoxic, quinoline -based alkaloid extracted from the Asian tree Camptotheca acuminata. Irinotecan, a prodrug, is converted to a biologically active metabolite 7-ethyl-10-hydroxy-camptothecin ( SN-38) by a carboxylesterase-converting enzyme.
How does irinotecan inhibit the action of topoisomerase?
Irinotecan inhibits the action of topoisomerase I. Irinotecan prevents religation of the DNA strand by binding to topoisomerase I-DNA complex. The formation of this ternary complex interferes with the moving replication fork, which induces replication arrest and lethal double-stranded breaks in DNA.
Is irinotecan considered an emetic agent?
Irinotecan is considered an antineoplastic agent of moderate emetic risk (i.e., incidence of emesis without antiemetics exceeds 30% but does not exceed 90%). Because nausea and/or vomiting occur frequently in patients receiving irinotecan therapy and may be severe, effective antiemetic therapy (e.g., dexamethasone
