8. Page1 8. B 1 5) 6) 2099 2370 50 400 mg 19 (1) 1) (a) 78.9% 30/38 4 3 35.7% 5/14 71.4% 10/1485.7% 12/142 1 83.3% 5/63 2 1 1 1
8. Page2 (b) 2099 1897 82.4% 1562/1897 2 84.0% 1298/1545 3 2 80.4% 472/58779.0% 592/74985.7% 6/7 85.3% 81/95 89.5% 411/459 2 a) b) 10/14 71.4% 472/587 80.4% 12/14 85.7% 592/749 79.0% 1/2 81/95 85.3% 5/6 83.3% 411/459 89.5% 2/3 6/7 85.7% 3/3 -/- 33/42 78.6% 1562/1897 82.4% a) b) 37 21 2.3% 37/1585 2 1585
8. Page3 2) (a) C. albicans MIC 90 =0.5 µg/ml C. parapsilosis MIC 90 =4 µg/mlc. tropicalis MIC 90 =1 µg/mlc. guillermondii MIC=2 µg/mlc. glabrata MIC 80 =8 µg/ml non-albicans Candida spp. Cryptococcus neoformans MIC 90 =16 µg/ml2.6.2.2(1)2)(b) Candida spp. 75.0% 24/32 2.7.3.3.2(2) Cryptococcus spp. 66.7% 4/6 2.7.6 No. UK-292,663-JP- -601 6)(d) MIC C. albicans 0.51 µg/ml non-albicans Candida spp. 1.49 µg/ml Cryptococcus spp. 5.28 µg/ml 3 C. albicans non-albicans Candida spp. Cryptococcus neoformans 3 MIC MIC µg/ml MIC C. albicans 31 0.51 0.125 >64 Non-albicans Candida spp. 28 1.49 0.25 4 C. glabrata 8 3.36 1 4 C. guilliermondii 2 2.83 2 4 C. lusitaniae 2 1.00 1 C. parapsilosis 13 1.00 0.5 4 C. tropicalis 3 0.79 0.25 2 Cryptococcus neoformans 5 5.28 4 16 71.1% 27/38 4 4 2.7.3.3.2(1) 91.7% 33/36 90.3% 28/31100% 5/52.7.3.3.2(1) B
8. Page4 (b) 50.0% 6/1275.0% 6/8100% 7/7100% 8/857.1% 4/7 2.7.3.3.2(3)1) 1 1 7 7 100% 59 96%3 2 85.7% 6/7 7, 8) Cryptococcus neoformans Cryptococcus neoformans AIDS 9) AIDS 100 10 9) 2099 10 0.48% 95 5 100% 5/5 3)
8. Page5 (2) 1) (a) 50 100 mg 50 200 mg 1 400 mg 50 200 mg 50 400 mg 200 mg 200 400 mg 400 mg 800 mg 4 400 800 mg
8. Page6 4 50 200 mg 50 200 mg 50 400 mg 50 100 mg 200 mg 200 400 mg 200 400 mg 50 200 mg 400 mg 400 mg 800 mg 400 mg 400 mg 400 mg 800 mg (b) 2099 1 200 mg 1491 1121 75.2% 608 424 69.7% 81.0% 1700/2099 67.9% 38/56 1 200 mg 77.2% 865/1121 89.4% 379/424 5 5 a) 1 400 mg 200 400 mg 100 200 mg 100 mg 170/217 78.3% 104/162 64.2% 5/6 (83.3%) 279/385 (72.5%) 23/28 82.1% 47/53 88.7% 70/81 (86.4%) 349/466 74.9% 865/1121 (77.2%) 379/424 (89.4%) 233/301 77.4% 351/433 81.1% 117/138 84.8% 168/214 78.5% 4/6 66.7% 8/10 80.0% 2/2 1/1 1/1 586/736 (79.6%) 35/42 83.3% 274/301 91.0% 309/343 (90.1%) 895/1079 82.9% a) 2099 286/353 (81.0%) 30/32 93.8% 115/133 86.5% 145/165 (87.9%) 431/518 83.2% 299/370 (80.8%) 157/184 (85.3%) 13/17 (76.5%) 4/9 44.4% 8/10 80.0% 12/19 (63.2%) 25/36 69.4% 524/662 79.2% 631/819 77.0% 9/10 90.0% 1164/1491 (78.1%) 92/111 82.9% 444/497 89.3% 536/608 (88.2%) 1700/2099 81.0% 100 mg 17.0% 8/47100 200 mg 11.1% 64/578200 400 mg 10.9% 134/1226400 mg 9.2% 48/519
8. Page7 6 % 6 1 400 mg 200 400 mg 100 200 mg 100 mg 48/519 134/1226 64/578 8/47 9.2% 10.9% 11.1% 17.0% 254/2370 10.7% 400 mg (c) B B 1 5) 200 400 mg 77%, 367/476 B 0.5 0.6 mg/kg 71%, 249/350 B B 45% 145/322 8% 15/181 7 10) 10) 7 B B 0.5 0.6 mg/kg/ 200 400 mg 77% 367/476 71% 249/350 45% 145/322 8% 15/181 B 6 1 400 mg 6) 1 1600 mg 2000 mg 1 800 mg 11) 400 mg 2000 mg 800 mg 1600 mg 800 mg 2) (a)
8. Page8 2.7.1.2(1) 2 1000 mg 793 mg 500 mg 397 mg 8 10 14.7 µg/ml 59 96% 54.9% 8 14 µg/ml 2.7.2.2(2)(b)d)2.7.2.2 (2)(b)d) 15 2.7.2.2(2)3)(a) Candida spp. MIC C. albicans 0.83 µg/ml non-albicans Candida spp. 2.0 µg/ml 2.7.3.2 (1)6)(e) MIC C. glabrata Crypcococcus neoformans MIC 80 8 µg/ml 2.6.2.2(1)2)b) PK 400/200 mg ) MIC 2.7.2.3.4)(3) PK MIC 1000 mg 2 C. albicans (b) 200 400 mg 100 200 mg 73.8% 31/42 8800 mg 2 400 mg 800/400 mg 81.8% 9/11400/200 mg 76.2% 16/21200/100 mg 62.5% 5/8400/200 mg 78.1% 25/32 200/100 mg 62.5% 5/8 8800/400 mg 81.8% 9/11400/200 mg 64.3% 9/14 400/200 mg 100% 7/7200/100 mg 62.5% 5/8 800/400 mg 400/200 mg 400/200 mg ) 504.5 mg 400 mg 2 252.3 mg 200 mg
8. Page9 8 800/400 mg 400/200 mg 200/100 mg 2/3 4/8 -/- 0/1 a) 6/12 50.0% 3/4 2/3 -/- 1/1 b) 6/8 75.0% 4/4 3/3 -/- -/- 7/7 100% 9/11 81.8% 9/14 64.3% -/- 1/2 19/27 70.4% -/- 4/4 4/4 -/- 8/8 100% -/- 3/3 1/4 -/- 4/7 57.1% -/- 7/7 5/8 12/15 -/- 100% 62.5% 80.0% 9/11 16/21 5/8 31/42 81.8% 76.2% 1/2 62.5% 73.8% 25/32 78.1% a) 800 mg 400 mg CLCr 200 mg b) 400 mg 200 mg 400 mg (c) 4 1 40 80 160 mg/kg 1 160 mg/kg/ 2.6.6.3(1) 1 7.5 36 90 mg/kg 1 90 mg/kg 36 mg/kg/2.6.6.3(3) 1 1 160 mg/kg 36 mg/kg 2.6.6.2(1) AUC1007 µg h/ml, 748 µg h/ml AUC 357 µg h/ml 3 2 1500 2000 mg/kg 2000 mg/kg 2 1,000 mg 793 mg 3 500 mg 397 mg
8. Page10 2000 mg 1600 mg 1000 mg 800 mg14 2.7.4.2.1(1) 23.2% 22/95 2 5.3% 5/95 2.7.4.2.1(2) 800/400 mg 27.8% 10/36 400/200 mg 23.5% 8/34 200/100 mg 6.7% 1/15 2.7.4.2.1.1(2)1)(b) 24.3%, 25/103 35 800/400 mg 18.5% 5/27 800/400 mg 2.7.4.2.1.1(2)2)(b) 3) 1/40 2 3 200 400 mg 73.8% 31/42 78.6% 33/42 72.7% 24/33 800/400 mg 400/200 mg 72.0% 18/25 400/200 mg 100% 7/7 200 mg 77.2% 865/1121 89.4% 379/424
8. Page11 800/400 mg 400/200 mg 100 200 mg 11.1% 64/578200 400 mg 10.9% 134/1226400 mg 9.2% 48/519 400 mg 800 mg 800 mg 200 400 mg 50 100 mg 50 200 mg 400/200 mg 800/400 mg 800/400 mg 100% 21/21 p.4 50 200 mg 63.1 126.1 mg 50 100 mg 63.1 252.3 mg 50 200 mg 2 1 504.5 mg 400 mg 2
8. Page12 63.1 126.1 mg 50 100 mg 1 1 2 126.1 252.3 mg 100 200 mg 63.1 252.3 mg 50 200 mg 1 1 2 126.1 504.5 mg 100 400 mg 504.5 mg 400 mg2 1009 mg 800 mg Infectious Diseases Society of America, Alexandria, VA 2000 12) 6 mg/kg/ 70 kg 400 mg 1997 13) 1998 14) 200 400 mg 1) Rex, JH, Bennett JE, Sugar AM, Pappas PG, van der Horst, CM, Edwards JE et al. A randomized trial comparing fluconazole with amphotericin B for the treatment of candidemia in patients without neutropenia. New Eng J Med 1994; 331: 1325-1330. 2) Nguyen MH, Peacock Jr JE, Tanner DC, Morris AJ, Nguyen ML, Snydman DR et al. Therapeutic approaches in patients with candidemia. Evaluation in a multicenter, prospective, observational study. Arch Intern Med 1995; 155: 2429-2435. 3) Anaissie EJ, Vartivarian SE, Abi-Said D, Uzun O, Pinczowski H, Kontoyiannis DP et al. Fluconazole versus amphotericin B in the treatment of hematogenous candidiasis: A matched cohort study. Am J Med 1996; 101: 170-176. 4) Viscoli C, Castagnola E, Van Lint MT, Moroni C, Garaventa A, Rossi MR et al. Fluconazole versus amphotericin B as empirical antifungal therapy of unexplained fever in granulocytopenic cancer patients: a pragmatic, multicentre, prospective and randomised clinical trial. Eur J Cancer
8. Page13 1996; 32A: 814-820. 5) Phillips P, Shafran S, Garber G, Rotstein C, Smaill F, Fong I et al. Multicenter randomized trial of fluconazole versus amphotericin B for treatment of candidemia in non-neutropenic patients. Eur J Clin Microbiol Infect Dis 1997; 16: 337-345. 6) Anaissie EJ, Kontoyiannis DP, Huls C, Vartivarian SE, Karl C, Prince RA et al. Safety, plasma concentrations, and efficacy of high-dose fluconazole in invasive mold infections. J Infect Dis 1995; 172: 599-602. 7) Saag MS, Graybill RJ, Larsen RA, Pappas PG, Perfect JR, Powderly WG et al. Practice guidelines for the management of cryptococcal disease. Clin Infect Dis 2000; 30: 710-718. 8). a). 1997; 33: 1706-1712. 9).. ;1999. P104-109. 10) Kontoyiannis DP, Bodey GP, and Mantzoros CS. Fluconazole vs. amphotericin B for the management of candidaemia in adults: a meta-analysis. Mycoses 2001; 44: 125-135. 11). AIDS. ; 1993: 59-73. 12) Rex JH, Walsh TJ, Sobel JD, Filler SG, Pappas PG, Dismukes WE et al. Practice guidelines for the treatment of candidiasis. Clin Infect Dis 2000; 30: 662-678. 13). Empiric Therapy Jap J Antibio 1997; 50: 669-682. 14). Jap J Antibio 1998; 51: 721-734.
8. Page14 (3) 100/200/400 606 9 4 25 607 9 4 25 (1) (1) (2) (3) [ (1)] 6 (1) (2) [ ] (3) [] (1) (2) (3) (2)
8. Page15 (1)) (2)
8. Page16 (1) 1
8. Page17
8. Page18 (2) 肝臓 皮膚 消化器 精神 神経系 腎臓 代謝異常 血液 循環器 呼吸器筋 骨格系 その他 (1) (2)
8. Page19 (2) (1) 1200 2000mg/ 1600mg/ 2000mg/ 18) (2) 8200mg 48 (1) [ ] (2) 10mL/ 10 28 1) 2)