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200mg

2005 3 876179 2002 3 3 200mg VFEND for Intravenous Use (1) (2) [4.1 ] (3) [4.2 ] (1) [1] (2) (3) [1] 3

<30mL/min [ SBECD ] 1 1 ph 200mg 200mg β 3200mg 5.57.019mL 10mg/mL 219mL 10mg/mL 1. 4

1 6mg/kg 1 2 2 1 3mg/kg 1 4mg/kg 1 2 19mL [] 1. [2.] 2. 3. Child Pugh AB 2 [6.(1)] 4. [] 1. (1) (2)[Child Pugh C ] (3)[(2) (1)] (4) 30mL/min50 ml/min[ SBECD [6.(3)]] 2. (1) 5

(2) (3) (4) (5) SBECD 1 3 mg/kg [] 3. CYP 2C192C9 3A4 CYP 2C192C9 3A4 (1) R R C max 93 AUC 96 1 CYP3A4 C max 69AUC 78 1 CYP3A4 R R R R C max 3.0 AUC 4.3 2 C max 61AUC 77 3 C max 1.4 AUC 1.4 3) C max 66AUC 82 4 CYP3A4 CYP2C19 CYP2C9 CYP3A4 CYP2C19 CYP2C9 CYP3A4 6

QT torsades de pointes R R R R R R CYP3A4 CYP3A4 (2) HIV NNRTI C max 49AUC 69 5 C max 1.7 AUC 1.8 5 CYP3A4 CYP2C9 In vitro CYP3A4 6 In vitro CYP3A4 6) In vitro CYP3A4 7 CYP3A4 C max 1.1 AUC 1.7 8 C max 2.2 AUC 3.2 9 1.9 10 In vitro CYP3A4 7) CYP3A4 CYP2C9 7

C max 2.2 AUC 3.8 11 HMGCoA CYP2C19 CYP3A4 In vitro CYP3A4 7),12 CYP2C9 CYP3A4 4. 100 78 78.0 13 25.024.0GTP 11.0 8.08.08.08.0ASTGOT7.0ALP 7.0ALTGPT6.05.05.05.0 5.0 (1) 1 2 StevensJohnson Lyell 3 12 4 QT QT torsades de pointes 5 6 8

7 8 9 10 11 (2) 5 15 * ADH / 9

5 15 * ALTGPT ASTGOT ALP GTP LDH D FDP * BUN 5. 6. (1) [ 10mg/kg 14) 100mg/kg 15) ] (2) 7. 8. 16),17 1600mg 10

9. (1) 19mL 10mg/mL 20mL 0.5 5mg/mL 5T1 T3 T3 G T4 F D 33 G R (2) 19mL 10. 4.5g/mL 4.5/mL 1. (1) 6 1.53 6mg/kg 8902107 4526ng/mL 3.24.4 6.4 AUC 2388 6412 18144ng h/ml (2) CYP2C19 CYP2C19 EM: Extensive MetabolizerHEM: Heterozygous Extensive MetabolizerPMPoor Metabolizer 11

6mg/kg 1 2 3 4mg/kg 1 2 10 (ng/ml) 7000 6000 5000 4000 3000 2000 1000 10 CYP2C19 C inf * (ng/ml) AUC (ng h/ml) 1/2 (h) EM 2 2830 11421 6.6 3 mg/kg HEM 2 3857 28832 6.3 PM 2 5529 46288 8.3 4 mg/kg EM 2 4525 18860 6.1 HEM 4 5697 37340 5.3 *: 投与量 :3 mg/kg EM (n=2) HEM (n=2) PM (n=2) 0 0 12 24 36 48 60 72 10 (h) 2. 96 20 III 100 21 3. 4.6L/kg 20) (1) 110 0.221.0 0.46 (2) 58 4. In vitro CYP2C19CYP2C9 CYP3A4 24 N 23 5. 23) 96 12

2 6. (1) 1 200mg 1 2 1 400mg 1 2 ChildPugh B 1 100mg 1 2 1 200mg 1 2 AUC 2 6 (2) 3050mL/min 1 6mg/kg 1 2 3mg/kg 5.5 AUC C max (3) SBECD [ β] 26 SBECD SBECD : 3050 ml/min AUC C max 5 1.5 (4) 4 SBECD 8 46 13

1. 13 ) 60 587 () / (1501001) (150307/602) (150309/604) 1/2 11/21 5/5 23/38 4/4 1/1 1/2 1/1 11/12 36/62 (91.7) 10/16 3/5 14/18 1/1 28/40 (70.0) 1/1 7/7 8/8 (100) 67/119 1/2 2/7 1/1 71/129 (55.0) (58.1) 40/86 4/12 5/9 4/7 53/114 (46.5) 1/4 0/1 3/9 1/2 1/1 6/17 (35.3) 1/2 1/1 2/4 0/1 4/8 (50.0) 0/3 1/2 2/2 0/1 3/9 (33.3) 47/60 71/129 102/210 (78.3) (55.0) (48.6) 0/1 (150608) 162/248 162/248 (65.3) 162/248 (65.3) 14

1. (1) in vitro 31 (2) 31 (3) 3241 2. 42 voriconazole 2R,3S22,4difluorophenyl35fluoropyrimidin4yl11,2,4triazol1ylbutan2ol C 16 H 14 F 3 N 5 O 349.31 F H N N H 3 C N OH F N N F 99.5 1mol/L log D1.69pH 7.41/ 15

1. 200mg 10 1)4 5) Purkins, L. et al. Br. J. Clin. Pharmacol. 56(s1): 37, 2003 6), 7R. Hyland et al. 8) Romero, A. J. et al. Clin. Pharmacol. Ther. 71(4): 226, 2002 9) 10) Purkins, L. et al. Br. J. Clin. Pharmacol. 56(s1): 24, 2003 11) 12) R. Hyland et al. 13 14 M. Leonard et al. 15 16), 17 18), 19 20 21 22 I. Lutsar et al. Clin. Infect. Dis. 37: 728, 2003 23) Roffey. S. J. et al. Drug Metab. Dispos. 31(6): 731, 2003 24) Hyland, R. et al. Drug Metab. Dispos. 31 (5): 540, 2003 25)27 28) Herbrecht R. et al. N. Engl. J. Med. 347 (6): 408, 2002 29) Perfect J. R. et al. Clin. Infect. Dis. 2003 (36): 1122, 2003 30) 31)42C. A. Hitchcock et al. 16

1518589 3227 0120664467 FAX 0333793053 1518589 3227 17