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1 200mg

2

3 mg VFEND for Intravenous Use (1) (2) [4.1 ] (3) [4.2 ] (1) [1] (2) (3) [1] 3

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

5 1 6mg/kg mg/kg 1 4mg/kg mL [] 1. [2.] 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

6 (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 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

7 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 CYP3A4 CYP2C9 In vitro CYP3A4 6 In vitro CYP3A4 6) In vitro CYP3A4 7 CYP3A4 C max 1.1 AUC C max 2.2 AUC In vitro CYP3A4 7) CYP3A4 CYP2C9 7

8 C max 2.2 AUC HMGCoA CYP2C19 CYP3A4 In vitro CYP3A4 7),12 CYP2C9 CYP3A GTP ASTGOT7.0ALP 7.0ALTGPT (1) 1 2 StevensJohnson Lyell QT QT torsades de pointes 5 6 8

9 (2) 5 15 * ADH / 9

10 5 15 * ALTGPT ASTGOT ALP GTP LDH D FDP * BUN (1) [ 10mg/kg 14) 100mg/kg 15) ] (2) ), mg 10

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

12 6mg/kg mg/kg (ng/ml) CYP2C19 C inf * (ng/ml) AUC (ng h/ml) 1/2 (h) EM mg/kg HEM PM mg/kg EM HEM *: 投 与 量 :3 mg/kg EM (n=2) HEM (n=2) PM (n=2) (h) III L/kg 20) (1) (2) In vitro CYP2C19CYP2C9 CYP3A4 24 N ) 96 12

13 2 6. (1) 1 200mg mg 1 2 ChildPugh B 1 100mg mg 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 (4) 4 SBECD

14 1. 13 ) () / ( ) (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/ /210 (78.3) (55.0) (48.6) 0/1 (150608) 162/ /248 (65.3) 162/248 (65.3) 14

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

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

17 FAX

1.8.2 Page MIC () MIC 50 / MIC 90 µg/ml Candida albicans (54) / Candida glabrata (25) 0.25 / 0.5 Candida guilliermondii a) (2)

1.8.2 Page MIC () MIC 50 / MIC 90 µg/ml Candida albicans (54) / Candida glabrata (25) 0.25 / 0.5 Candida guilliermondii a) (2) 1.8.2 Page1 1.8.2 96% 2002 40 B 1 123 (1) in vitro 1) in vitro C. glabrata C. krusei 1 2 19951997 3 1999 2002 MIC MIC 2 1.8.2 Page2 1 19951997 MIC () MIC 50 / MIC 90 µg/ml Candida albicans (54) 0.016 /

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