Y S P 20 / Innocan Conc. Solution for I.V. Infusion 20mg/ml INI -001 049890 ml Irinotecan Hydrochloride Trihydrate. 20mg 5-FU folinic acid 5-FU Irinotecan ( ) Irinotecan 350mg/m 2 30 90 ( ( ) Irinotecan 5-fluorouracil(5-FUfolinic acid(fa ( Irinotecan 5FU/FA Irinotecan 180mg/m 2 30-90 folinic acid 5-fluorouracil NCI-CTC( 0 1 Irinotecan Irinotecan 5FU ( 1 2 Irinotecan / 5-FU( ) 15-20% ( 4 ( 3-4 2-4 (4 ) (3-4
Irinotecan 2 Irinotecan ( (ULN3 酶 50% Irinotecan ( ) (ULN1.5 Irinotecan 350mg/m 2 (ULN1.5-3 Irinotecan 200mg/m 2 3 Irinotecan ( Irinotecan Irinotecan ( ( / ( ) Irinotecan hydrochloride trihydrate ( ) > 3 ( ) WHO > 2 (St John s Wort ( ) Irinotecan Irinotecan WHO = 2 (
Irinotecan ( Irinotecan 24 Irinotecan 5 / 2 Irinotecan Irinotecan loperamide( 4mg 2 2mg) 12 loperamide 48 12 ( < 500 /mm 3 ( loperamide 48 loperamide ( Irinotecan ( > 38 1,000 /mm 3 ( Irinotecan (
1.5 3 Irinotecan ( 3 Irinotecan Irinotecan ( ) atropine sulphate (0.25mg Irinotecan atropine sulphate Irinotecan (colony stimulating factors Irinotecan ( ) Irinotecan ( Irinotecan ( ( / Irinotecan CYP3A4 ( ketoconazole ( rifampicin carbamazepine phenobarbital phenytoin Irinotecan ( Irinotecan Irinotecan 酶 酶 (suxamethonium CYP3A ( carbamazepine phenobarbital
phenytoin) Irinotecan SN-38 SN-38 SN-38 SN-38G (AUC 50% P450 3A Irinotecan Irinotecan Irinotecan ketoconazole APC (aminopentanoic acid AUC 87% SN-38 AUC 109% ( ketoconazole ( rifampicin carbamazepine phenobarbital phenytoin P450 3A4 Irinotecan ( (n=5irinotecan 350mg/m 2 (Hypericum perforatum) 900mg Irinotecan SN-38 42% SN-38 Irinotecan ( 5-fluorouracil/folinic acid irinotecan Irinotecan Irinotecan Irinotecan( Irinotecan ( 14 C-Irinotecan Irinotecan Irinotecan ( Irinotecan 24 765 Irinotecan 350mg/m 2 145 Irinotecan 180mg/m 2 5FU/FA 2 Irinotecan ( 24 Irinotecan
20% 14% Irinotecan 5 13.1% 3.9 ( [Clostridium difficile] 10% ( 2.1% 2.8% / / - Irinotecan / loperamide 10% 3.4% (intestinal obstruction ileus ( 8 78.7% ( < 500 /mm 3 22.6% 18% 1,000 /mm 3 7.6% < 500 /mm 3 22 6.2% (1.7% ) 10.3% (2.5% 5.3% (1.1% ) 2 58.7% ( 8% [Hb] < 8 g/dl 0.9% Hb < 6.5 g/dl 7.4% (1.8% (< 100,000 /mm 3 0.9% (0.2% ) 50,000 /mm 3 22
82.5% ( < 500 /mm 3 9.8% 67.3% < 1,000 /mm 3 2.7% < 500/mm 3 7-8 3.4% (0.9% ) 2% (0.5% 2.1% (0.5% ) 1 97.2% (2.1% Hb < 8 g/dl 32.6% (21.8% ( < 100,000 /mm 3 ( < 500,000 /mm 3 9% 1.4% Irinotecan 24 atropine ( 10% 6.2% Irinotecan 12% 6.2% Irinotecan ( / (anaphylactic/anaphylactoid reactions)
9.2% 8.1% 1.8% 酶酶 7.3% 15% 11% 11% 10% SGPT SGOT 酶 (1 2 0% 0% 0% 1% 3 4 酶 / 酶 Irinotecan 2 Irinotecan 酶 (topoisomerase I (Anatomical Therapeutic Chemical ATC codel01xx19 Irinotecan (camptothecin) DNA 酶 酶 SN-38 酶 Irinotecan Irinotecan Irinotecan SN-38 DNA 酶 DNA (replication fork S Irinotecan SN-38 P- MDR (P-glycoprotein MDR doxorubicin vinblastine Irinotecan (P03 MA16/C C38 C51 (Co-4 Mx-1 ST-15 SC-16 Irinotecan P- MDR ( vincristine doxorubicin P388 Irinotecan 酶
/ 980 5-FU 5-FU 765 Irinotecan Irinotecan Irinotecan 5FU Irinotecan p Irinotecan 5FU p n = 183 n = 90 n = 127 n = 129 6 NA NA 33.5* 26.7 p = 0.03 (%) 12 (%) 36.2* 13.8 p = 0.0001 44.8* 32.4 p = 0.0351 ( ) 9.2* 6.5 p = 0.0001 10.8* 8.5 p = 0.0351 NA * 455 6 30% 9 18 304 125mg/m 2 90 17 10 193 125mg/m 2 11 385 ( Irinotecan Irinotecan 180mg/m 2 folinic acid (200mg/m 2 2 5-fluorouracil (400mg/m 2 600mg/m 2 22 folinic acid 5- fluorouracil Irinotecan 80mg/m 2 folinic acid (500mg/m 2 2 ) 5-fluorouracil (2300mg/m 2 24 ) 198 Irinotecan (p = 198) (n = 50) (p = 148) Irinotecan Irinotecan 5FU/FA + 5FU/FA + 5FU/FA 5FU/FA Irinotecan + 5FU/FA 5FU/FA (%) 40.8* 23.1* 51.2* 28.6* 37.5 21.6* p p < 0.001 p = 0.045 p = 0.005
Irinotecan 5FU/FA EORTC QLQ-C03 ( ) 6.7 4.4 7.2 6.5 6.5 3.7 p p < 0.001 NS p = 0.001 ( ) 9.3 8.8 8.9 6.7 9.3 9.5 p NS p = 0.043 NS 8.6 6.2 8.3 6.7 8.5 5.6 ( ) p < 0.001 NS p = 0.003 p 5.3 3.8 5.4 5.0 5.1 3.0 ( ) p p = 0.0014 NS p < 0.001 16.8 14.0 19.2 14.1 15.6 13.0 ( ) p p = 0.028 NS p = 0.041 5FU 5-fluorouracil FA folinic acid NS * 44.4% 5FU/FA 25.6% ( < 500 /mm 3 Irinotecan 5FU/FA 5.8% 5FA/FU 2.4% Irinotecan 5FU/FA (p = 0.046 Irinotecan / Irinotecan Irinotecan / Irinotecan ( SN-38 (AUC) ( Irinotecan SN-38 AUC 60 100-750mg/m 2 30 Irinotecan 15L/h/m 2 (Vdd157L/m 2 12 2.5 14.2 SN-38
13.8 350mg/m 2 Irinotecan SN-38 7.7 g/ml 56ng/ml (AUC 34 g h/ml 451 ng h/ml SN-38 148 Irinotecan Irinotecan (CPT-11 SN-38 CPT-11 Irinotecan SN-38 65% 95% 14 C- 50% Irinotecan 33% 22% 12% 酶 SN-38 SN-38 ( 0.5% Irinotecan SN-38 P450 3A (piperidine APC (aminopentanoic acid NPC ( primary amine derivate)( Irinotecan APC SN-388 SN-38 SN-38 1.5 3 Irinotecan 40% Irinotecan 200mg/m 2 350mg/m 2 Irinotecan SN-38 CHO (chromosomal aberrarion test) Ames 150mg/ m 2 ( 13 91 Irinotecan
Irinotecan ( Irinotecan 12 2-8 24 ( ) Irinotecan Irinotecan Irinotecan Irinotecan ( ) Irinotecan 250ml 0.9% 5% 25 5ml 100
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