生物活性

• 描述Irinotecan, a derivative of camptothecin improved in therapeutic efficacy, is a Topoisomerase I inhibitor with IC50 values of 1.32 μM and 1.53 μM for induction of formation of DNA-topoisomerase I cleavable complexes in LoVo cells and HT-29 cells, respectively. Irinotecan is effective on anti-proliferation against tumor cells, including vincristine- and Adriamycin-resistant P388 leukemia cells with IC50 values of 3μM and 9μM, respectively. Irinotecan at concentration of 30μM for 24h significantly increased the proportions significantly increased the proportions at the S and G2 /M phases of cell cycling and decreased population at the G1 phase in both Caco-2 and CW2 cells, but no apoptosis or necrosis observed. Irinotecan showed significant antitumor activity against a broad spectrum of experimental tumor models by i.p., i.v., or oral administration, including susceptible murine tumors SISO, Meth A fibrosarcoma, Lewis lung carcinoma, Ehrlich carcinoma, MH134 hepatoma, mammary carcinoma of C3H/HeN mice, LI 210, and P388 leukemia, at doses ranging in 25-800mg/kg, with low acute toxicity. The difference in efficacy of CPT-11 between species may be related to the metabolism of the drug, since CPT-11 is converted more efficiently into SN-38 in mice.

• 动物研究
  剂量	Mice: 5 mg/kg - 75 mg/kg[3] (p.o./i.v.) MTD: 240 mg/kg[4] （i.p., BALB/c Mice) Rat: 65 mg/kg - 130 mg/kg[5] (i.v.)
  给药途径	p.o., i.v., i.p.
  动物药代数据	Animal Mice[3] Dose 10 mg/kg Administration i.v. or p.o. Tmax 1 h (p.o.) T1/2β 2.1 h (i.v.) 1.1 h (p.o.) CL 24.8 L/h/m2 (i.v.) Cmax 1796 ng/ml (i.v.) 74 ng/ml (p.o.) AUC0→∞ 1301 ng·h/ml (i.v.) 154 ng·h/ml (p.o.) Vss 21.6 L/kg (i.v.)

• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT00813072	Stomach Neoplasms ... more >> Esophageal Neoplasms Collapse <<	Phase 2	Completed	-	Bosnia and Herzegovina ... more >> Clinical Hospital Mostar Mostar, Bosnia and Herzegovina, 36 000 Clinical Centre University of Sarajevo Sarajevo, Bosnia and Herzegovina, 71 000 Croatia University Hospital Centre Rijeka Rijeka, Croatia, 51 000 University Hospital Centre Dubrava Zagreb, Croatia, 10 000 University Hospital Centre Zagreb Zagreb, Croatia, 10 000 Korea, Republic of Samsung Medical Center Seoul, Korea, Republic of, 135-710 Asan Medical Center Seoul, Korea, Republic of, 138-736 National Cancer Center Seoul, Korea, Republic of, 410-769 Spain Hospital Universitario Vall d'Hebron Barcelona, Spain, 08035 Hospital General Universitario de Elche Elche, Spain, 03203 Hospital Clínico San Carlos Madrid, Spain, 28040 Hospital Universitario Marques de Valdecilla Santander, Spain, 39008 Taiwan Chang Gung Memorial Hospital - Chiayi Chiayi, Taiwan Chang Gung Memorial Hospital - LinKou LinKou, Taiwan National Cheng Kung University Hospital Tainan, Taiwan, 704 Taipei Veterans General Hospital Taipei, Taiwan, 112 Mackay Memorial Hospital Taipei, Taiwan, 25115 United Kingdom Addenbrookes Hospital Oncology Center Cambridge, United Kingdom, CB2 2QQ Guy's & St Thomas' NHS Foundation Trust London, United Kingdom, SE19RT Kent Oncology Centre, Maidstone Hospital Maidstone, United Kingdom, ME16 9QQ Southampton University Hospital Southampton, United Kingdom, SO16 6YD The Royal Marsden Hospital Surrey, United Kingdom, SM2 5PT Collapse <<
  NCT02275806	Lung Neoplasms, Non-Small Cell... more >> Lung Cancer Collapse <<	Phase 2	Terminated(PI decided to termi... more >>nate study) Collapse <<	-	United States, North Carolina ... more >> Leo W Jenkins Cancer Center Greenville, North Carolina, United States, 27834 Collapse <<
  NCT00836277	Esophageal Cancer	Phase 2	Completed	-	United States, Pennsylvania ... more >> University of Pittsburgh Cancer Institute Pittsburgh, Pennsylvania, United States, 15232 Collapse <<

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• 参考文献

• [1] Tobin P, Clarke S, et al. The in vitro metabolism of irinotecan (CPT-11) by carboxylesterase and beta-glucuronidase in human colorectal tumours. Br J Clin Pharmacol. 2006 Jul;62(1):122-9.

  [2] Pavillard V, Agostini C, et al.Determinants of the cytotoxicity of irinotecan in two human colorectal tumor cell lines. Cancer Chemother Pharmacol. 2002 Apr;49(4):329-35.

  [3] Stewart CF, Zamboni WC, et al. Disposition of irinotecan and SN-38 following oral and intravenous irinotecan dosing in mice. Cancer Chemother Pharmacol. 1997;40(3):259-65.

  [4] Aston WJ, Hope DE, et al. A systematic investigation of the maximum tolerated dose of cytotoxic chemotherapy with and without supportive care in mice. BMC Cancer. 2017 Oct 16;17(1):684.

  [5] Onivyde

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