2010 12 19 6 401 (2010) 1995 2 Ca 2+ Ca 2+ 12 FDA 90 TdP 15 2007 2006 ACC/AHA/ESC SFDA 3 <90 2010 4 ACC/AHA Torade de Point TdP 1 50%~90% 30%~70% TdP 2 TdP TdP 3 TdP K + K + TdP TdP TdP Ikr 3 TdP TdP K + Iks TdP 2 3 Iks K + 3 10 :1Ikr Ikr TdP 2 Ikr Iks Tedisamil 3Iks Ikr Ikr M 3 QT M TdP : 2 Na + Na + 1Pubmed 2010 4
402 J Clin Electrocardiol,2010,Dec.19.No.6 2 3 AASLD EASL APASL 2009 β- 4 1. Fumarate ibutilide [1-3] 100g/L PH 7.0 + - :±N- [4-4- - 1- ] 1: 0.5 N 22 H 38 N 2 O 5 S 442.62 1 1 [16] 2. QTc K + Ikr 2 QT Ca 2+ 2 Na + Ca 2+ TdP QTc 3. [4-8] 1 K + K + 1 Ikr K + Ik Ikr Iks K + [17] [9] [18] Ik 1 Ikr Ikr Ikr 2 [2] K + [13 17 19] [12 20 21] QT QTc [10-12] Ikr 3 3 QT 2 Na + 0 Na + 2 [12] [22 23] QT QTc 3 AH [24] INa INa INa 4 His - His - [13-14] INa 0 Vmax [15] [24] 0 5 QT [12 17 25] [24] 3 Ca 2+ Ca 2+ L- Ca 2+ [13] K + Ca 2+ Na + 2 6 2 Ca 2+
2010 12 19 6 403 [24] 1. 1 [5] 18 6.6~13.4L/min 11L/kg 40% 29 ml min - 1 kg- 1 2~12h 6h [5] 80% 7 2007 0.01mg/kg 82% 7% [28] [5] 18% 5%. ~10% 1. [3 5] [29] 2 19± 15min 31%~77% 54%~87% [30-36] [3 5] β 2006 ACC/AHA/ESC 1 :Ia 4h 2 QT QT 1 TdP QT 10%~40% 2006 ACC/AHA/ESC 2~6h QTc 10min IIa B VanderLugt [37] 0.03mg/kg 8h 1~7 0.01mg/kg QTc 36% 45% [5] 3 302 1~3h 201 101 69% 20% 11% 31% 2. <40% 0.03mg/kg 15% [26] 0.06mg/kg 0.25mg 0.5mg 1.0mg 40% PR QRS 47% 57% 2 <35% Hans [27] <48h 132 / 77 /
404 J Clin Electrocardiol,2010,Dec.19.No.6 A Wood [41] 55 21 44% [42] 3. 1 2006 ACC/AHA/ESC 3 IIa B Li [43] 12 11 [44] 92% 100 50 1.0mg 50 100% vs. 72% p=0.001 166±80J vs. 228±93J p<0.001 14 64 2 20% 4 2006 ACC/AHA/ESC Volgman [45] 127 3h~90 a C 76% vs. 14%, b B p=0.001 51% vs. 21% p=0.005 C 3 2007 Kafkas <90 [46] 152 <30 TdP 6 2 3~48h 2. 80% vs. 57% p=0.0054 1 87% vs. 29% p=0.003 77% vs. 69% p=ns [38] Eidher [39] 38 4 [30] 39 38.8% 212 66.6% vs. 28.6% p=0.05 78.1% vs. 272±49bpm vs. 207±36bpm p<0.004 48.3% 0.05 54.7% vs. 39.5% p> 0.05 >3 < 90 2 [40] 1 34 33 1. 90% 65% 54%~87% 21±19min 35±8min 31%~77% 3 2.
2010 12 19 6 405 2 3 QTc QTc >440ms 3. 4 18~75 60~100kg >75 <60kg 0.01mg/kg 5 <90 >90 4. <45mm 6 5. 6. 65 110mmHg 7. 8 8. >4.0mmol/L 9. 10. 2 1. 11.. 1. 1 2 3 2.0~3.0 4QTc >440ms 2. 1 <3.5mmol/L <0.8mmo/L 2 5. <55bpm 3 <35% 4 [47] <40% 5 1 6. 2 7 QT 1. [51] 1 [42 47 48] 8 >60kg 1.0mg 0.9% 20ml 9 18 10min <60kg [49] 1 10min QTc <60ms 2 >55bpm 3QTc 440ms 4 48h 3 INR 2.0~3.0 7 >55bpm 90~150mmHg 50~ <3.5mmol/L 9 2. 3. >48h 3 INR 4. 0.01mg/kg 2 >60kg 4.0mmol/L 5 TdP 6 1.0mg <60kg 0.01mg/kg QT Ic 7 QT 2.0mg 8 30min 19~32.5min [50] 16±9min 23±17min. 1 3 TdP QT 1.0mg
406 J Clin Electrocardiol,2010,Dec.19.No.6 10min 15min 2/6 33% 1/2 50% 30~35min [52] p=0.6 2. 80% I 4 42% TdP - 1.0mg 2.0mg Kalus [58] 321 <2h β 19% p=0.04 34% p=0.045 p=0.045 Caron [59] 20 I 10min 2.0g QT QTc 30min QTc β QTc >500ms [49 53] TdP 1 β β Fragakis [50] 100bpm 90 1. >60kg 0.9% 17±35 1.0mg 20ml 10min <60kg 0.01mg/kg 10min 67% vs. 46% p=0.04 QT 433ms vs. 501ms, 10min p=0.003 10min 2.0g 1h 3 2. 2 100bpm [54] 3. Korantzopoulos [55] 100 600mg 1.0mg 2.0mg Ic 71.4% vs. 41.1% p=0.0044 4. 20min vs. 32min p=0.0019 1 TdP 3 5. QT QTc Glatter [56] Oral [57]. 25 QTc 2 10 60ms 15 1.0mg 300mg
2010 12 19 6 407 4h QTc [60] QTc PR QRS QT QTc 2min QT 4h 440ms 420ms QT TdP QTc >500ms TdP LQTS QTc 480ms 4% QTc 470ms TdP TdP 2~3 [61] Ikr 40min 1h Ikr [60] TdP 5.6%~13.2% Ikr QT 45min [50 60] TdP L QT [56] QT [28 49] [62] QTc TdP 2 QT TdP 1 2 QTc >60ms 3 <50bpm 4 5 TdP 6 <90mmHg 7 8QRS 50% TdP [46] 9 10 2. 4 1. QTc QT Ikr QRS 2. QTc >60ms TdP <50bpm TdP <90mmHg QRS 50% Ikr Iks 3. 1 4h QTc 12 TdP QTc 2 3. TdP 4h 3 4 20% QTc TdP TdP QT TdP 3.6mmol/L 10%~40% 50% TdP TdP TdP 1.
408 J Clin Electrocardiol,2010,Dec.19.No.6 2 QT Ikr Iks 1 3 1 [65] Na + ST 2Ikr T Ikr Ikr 3 TdP 2Iks K + 3 3 Ito Ik Na + - K + Iks Na + Na + - Ca 2+ Ca 2+ 3 Ca 2+ QT TdP 4 Ikr Ikr 5. LQTS QT LQTS LQTS LQTS 50% [63] TdP LQTS K + 4. Na + QT 50% LQTS TdP 15%~20% TdP [66] 6. remodelling of cardiac repolarization QT Iks Iks Iks [64] Iks
2010 12 19 6 409 3 Ikr Mine M TdP TdP 7. QT TdP 4 TdP A. RR TdP B. TdP
410 J Clin Electrocardiol,2010,Dec.19.No.6 5%~7% 2 TdP QTc>500ms TdP 4 [67] 3 T T Tp- Te TdP 2 4 TdP QT TdP QT TdP TdP RR TdP 8. 5. QTC >500ms QT 5 [68~70] TdP K + QTc 6. Tdp TdP 45min 45min TdP 5 QT 2h 4h TdP TdP. TdP QT 1. TdP TdP TdP 4% TdP 7. Tdp 1.7% 0.8% 1 2. Tdp Ikr 2 Na + Ca 2+ TdP 3. TdP 1 QRS 2 T TdP 3 TdP RR 160~240 / 1 Perry M, Stansfeld PJ, Leaney J, et al. Drug binding interactions in 4 TdP 2~3 RR TdP the inner cavity of HERG channels: molecular insights from structure- activity relation- ships of clofilium and ibutilide analogs. 5 TdP Mol Pharmacol, 2006, 69 2 :509-519. Epub 2005, 16. 4. TdP 2 Perry M, de Groot MJ, Helliwell R, et al. Structural determinants of HERG channel block by clofilium and ibutilide. Mol Pharmacol, 1 QTc >470ms 10ms TdP 2004, 66 2 :240-249.
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