IRINOTECAN (CPT‐11): A BRIEF OVERVIEW

摘要: 1. Irinotecan (also known as CPT-11) is a water soluble, semi-synthetic analogue of 20(S)camptothecin (CPT) with promising activity against range tumour types. 2. As all other active analogues CPT, irinotecan causes cell toxicity by stabilizing ternary complex between the nuclear enzyme topoisomerase I (topo I) and double-stranded DNA. This leads to replication fork-arrest, double DNA strand breaks and, possibly, illegitimate recombination vital genes. 3. much greater for its metabolite SN-38 widely considered be prodrug SN-38. 4. The anti-topo CPT stereoselective at C-20 synthesized from 20(S)CPT ensure maximal activity. In aqueous solutions, lactone ring undergoes reversible spontaneous hydrolysis ring-opened inactive carboxylate form. patients, it has been shown that predominant form in plasma, whereas opposite true irinotecan. 5. transformation catalysed carboxylesterases. However, this conversion appears relatively inefficient man. 6. show evidence metabolic reactions (type II), some which could subject pharmacogenetic variability. 7. Therapy associated unusual toxicities, such an acute cholinergic-like syndrome delayed onset diarrhoea. Although mechanism diarrhoea remains defined, cholinergic due inhibition acetylcholinesterase.