2006 10 2007 02 2010 08 2010 11 2015 02 2015 05 2017 03 Valganciclovir Hydrochloride Tablets Yan Suan Xie Geng Xi Luo Wei Pian 1.L-,- 2[(2-- 1,6- -6-- 9H-- 9-) ]-3-- 2.9-[[2--1- ] ] L- O H H 2 N N N N N O OH O O NH 2. HCl C 12H 22 N 6 O 5 HCl 390.83 CMV CMV 450mg () Page 1 of 16
--- 10 CMV CMV 900mg 450mg 21 CMV CMV 900mg 450mg CMV 900mg 450mg 10 200 900mg 450mg 10 100 1 CrCl (ml/min) / 60 900 mg 2 900mg 1 40-59 450 mg 2 450 mg 1 25-39 450 mg 1 450 mg 2 1 10-24 450 mg 2 1 450 mg 2 < 10 [ ] - = m =0.85 (CrCl< 10 ml/min) Page 2 of 16
() 500/μl 25,000/μl, 8 g/dl AIDS CMV 79 28 21 7 2 2 n=79 n=79 16 % 10 % 11 % 6 % 9 % 5 % 8 % 4 % 8 % 14 % -- 6 % 3 5%, CMV 3 n=370 900mg 900mg CMV 65% 9 30 n=370 % 38% 26% 25% 24% 22% 21% 14% 13%9% Page 3 of 16
CMV 3 5%, n=244 n=126 10 100 28 n=244 30% 28% 24% 23% 22% 21% 20% 20% 20%18% 16% 100 CMV 2% 18% 10% 14% 9% 100 9% 7% 6% 5% 200,, 3 CMV 5% CMV 100 n=370 % n=244 % n=126 % 38 30 29 25 23 23 20 16 14 13 14 14 6 20 20 6 9 6 4 12 10 2 6 6 9 6 26 13 14 20 13 15 5 21 16 3 5 7 1 11 9 1 6 7 4 6 6 24 8 3 22 12 15 5 5 5 4 14 7 Page 4 of 16
20 3 3 / 12 4 8 10 3 9 7 7 9 7 4 2 6 1 6 5 11 9 18 22 27 14 20 16 7 1 1 6 5 5 2 28 25 9 10 6 ( ) 18 4 5 7 3 4 6 7 4 ( ) <1 9 4 <1 6-16 6 8 9 11 10 5 2 2 2 4 6 <1 7 8 13 6 1 4 9 7 6 9 3 3 1 10 14 8 20 15 6 7 7 2 6 11 3 5 7 1 7 12 2 7 6 24 30 5 3-5 - - <1 14 14 Page 5 of 16
2 8 8 <1 8 8 1 6 7 8 4 5 6 5 6 <1 9 6 <1 4 6 3 9 11 1 12 8 2 13 7 1 11 6 5 9 <1 5 6 1 3 8 3 18 15 (n= 934) 5%, :, CMV ANC <500 /ul 16%9 100 3% (10%) 200 CMV 100 200 200 200,, Page 6 of 16
- 100 4 200 4 CMV 100 n=370 % n=244 % n=126 % ANC/μl <500 16 5 3 500--<750 17 3 2 750--<1000 17 5 2 g/dl <6.5 7 1 2 6.5--<8.0 10 5 7 8.0--<9.5 14 31 25 /μl <25,000 3 0 2 25,000--<50,000 5 1 3 50,000--<100,000 21 18 21 mg/dl >2.5 2 14 21 >1.5--2.5 11 45 47 Page 7 of 16
( ) 500/mL 25,000/mL, 8 g/dl 10 11 / CrCl < 10 ml/min - - Page 8 of 16
90 12% - - 20%40% AUC 17% Page 9 of 16
3g 6g AU 84124% 5 10mg/kg/ 3867% MMF MMF MPAG MPA MMF MMF AUC 0-8 13% 16.3% 15% AUC 0-8 C max C min 12% B, / Page 10 of 16
10( ) EXP () 2 -, -1-2HSV-1HSV-2-678HHV -678EB - VZV CMV UL97 HSV HCMV 18 6~24 DNA a DNA DNA b DNA DNA CMV IC 50 0.08μM0.02ug/ml 14μM3.5ug/ml Page 11 of 16
AIDS WV15376 CMV 46%32/69 7%4/55 CMV CMV AIDS CMV CMV CMV 900mg CMV 226160 219125 CMV CMV CMV CMV D+/R - 10 900mg 1000mg 100 CMV CMV 6 CMV n=239 12.1%n=125 15.2% 100 CMV 6 29.7%n=125 36.0% 326 CMV D+/R- CMV 100 200 1:1 900mg 1 10 200 900mg 1 10 100 100 CMV 200 12 CMV 200 100 12 CMV 5 5 CMV 1 12 Cochran- 900mg, 1 900mg, 1 Mantel- 100 200 Haenszel 71/163 2 CMV (43.6%) CMV 60/163 (36.8%) 36/155 (23.2%) 25/155 (16.1%) p- 0.0001 <0.0001 Page 12 of 16
1 CMV CMV 2 CMV CMV 52 CMV CMV 12 100 98.2%160/163 200 98.1%152/155 12 100 17.2% 28/163 200 11.0%17/155 DNA UL54 UL97 UL54 UL97 UL54 UL54 V II 696-742 III 805-845 CMV 148 CMV PMNL CMV 361218 2.2%6.5%12.8%15.3% UL97 CMV 100 6 CMV PMNL CMV 245 198 100 103 2 1.9% 245 50 CMV 125 29 CMV 2 6.9% D+/R - 100 200 100 5 200 4 6 pul97 100 A440V M460VC592G 200 M460VC603W 3 pul54 100 E315D 200 E315D P522S 5/12 [42] 4/58 ] [ 7 Page 13 of 16
110mg/ml HIV CMV AIDS CMV 60% 24 AUC 24C max 1%3% 4502625mg AUC 900mg AUC 24 C max 30%14% 0.551μg/ml 12% 0.680±0.161/kg 1000mg 12% 81.5±22% Page 14 of 16
CrCl< 10 ml/min 450mg 4 n=28 900mg 60% AUC 0-24h 5mg/kg 30 C 60 / 36 Roche (Schweiz)Ltd. Pharma Schoenmattstrasse -4153 2 CHReinach Switzerland Patheon Inc. 2100 Syntex Court, -Mississauga, CDN Ontario, Canada, L5N 7K9 F.Hoffmann- La Roche AG Wurmisweg 4303 Kaiseraugst Switzerland 1100 021 28922888 021 50801800 8008208780 4008208780 Page 15 of 16
www.roche.com.cn Page 16 of 16