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Irinotecan is a hydrophilic compound with a large volume of distribution (400 L/m 2). [20] [21] At physiological pH, irinotecan and its active metabolite ethyl-10-hydroxy-camptothecin (SN-38) are present in two pH-dependent equilibrium isoforms; the anti tumor active lactone ring which hydrolyzed to the carboxylate isoform. [21]
It is the active metabolite of irinotecan (an analog of camptothecin - a topoisomerase I inhibitor) but has 1000 times more activity than irinotecan itself. In vitro cytotoxicity assays show that the potency of SN-38 relative to irinotecan varies from 2- to 2000-fold.
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Also, the doses (Day 1: irinotecan 165 mg/m2 IV, plus oxaliplatin 85 mg/m2 IV; Day 1: leucovorin 400 mg/m2; Days 1–3: fluorouracil 1,600 mg/m2/day × 2 days (total 3,200 mg/m2 over 48 hours) continuous infusion starting on day 1; Day 1: bevacizumab 5 mg/kg IV; repeat cycle every 2 weeks) [1] [8] [9] are slightly dissimilar to FOLFIRINOX.
Sacituzumab govitecan is a conjugate of the humanized anti-Trop-2 monoclonal antibody linked with SN-38, the active metabolite of irinotecan. [20] Each antibody having on average 7.6 molecules of SN-38 attached. [21] Linkage to an antibody allows the drug to specifically target cells expressing Trop-2.
Camptothecin (CPT) is a topoisomerase inhibitor.It was discovered in 1966 by M. E. Wall and M. C. Wani in systematic screening of natural products for anticancer drugs.It was isolated from the bark and stem of Camptotheca acuminata (Camptotheca, Happy tree), a tree native to China used in traditional Chinese medicine.
Camptotheca (happy tree, cancer tree, or tree of life) is a genus of medium-sized deciduous trees growing to 20 metres (66 ft) tall, native to southern China and Tibet. The genus is usually included in the tupelo family Nyssaceae, but sometimes included (with the tupelos) in the dogwood family Cornaceae.
In February 2024, Ipsen received FDA approval for Onivyde (irinotecan liposome injection), which is used in combination with oxaliplatin, fluorouracil, and leucovorin (NALIRIFOX) for the first-line treatment of patients with metastatic pancreatic adenocarcinoma (mPDAC). Pancreatic cancer accounts for approximately 3% of all cancer diagnoses in ...