CellCept

2007 02 14 2007 11 06 2008 01 22 2009 12 14 2010 01 18 2011 09 14 2012 07 16 2013 05 08 2014 11 03 2015 12 01 2016 06 03 2016 11 04 Mycophenolate Mofetil Tablets Matimaikaofenzhi Pian /

(E) -6-(4- -6- -7- -3-- 1,3- -5- ) -4-- 2-(- 4- ) C 23H 31 NO 7 433.49 A 0.5 g 1 g bid 2 g 1.5 g bid 3 g 2 g 3 g 0.5~1 g bid 1~2 g MPA AUC MPA C max 40% /

1 g bid 0.5~1 g 25ml/min/1.73m 2 1 g bid <1.3 1 3 /μl 3 g /

1 2 g 3 g 0.4% 1% 1.6% 3.2%0.7% 2.1% 3 1 1 3 42 3.9% 2g 3 g 1 2 g / 13.5% 3 18 100 3 18 600 mg/m 2 1 10% 6 65 /

3 2 3 g g 10% 3%~<10% 4% 10% 3%~<10% n = 991 * n = 289 ** n = 277 *** 10% 3%~< 10% /

n = 991 * n = 289 ** n = 277 *** 10% 3%~< 10% 10% 3%~< 10% 10% 3%~< 10% /

/ 10% 3% ~< 10% 10% n = 991 * n = 289 ** n = 277 *** BUN BUN AST ALT - γ AST ALT AST ALT AST ALT /

n = 991 * n = 289 ** n = 277 *** 3% ~< 10% AST AST ALT ALT 10% 3% ~< 10% 10% 3% ~< 10% 10% /

n = 991 * n = 289 ** n = 277 *** 3% ~< 10% 10% 3% ~< 10% 10% 3% ~< 10% 10% 3% ~< 10% PTH * n=1,483 ** n=578 *** n=564 2 3 PML PML BK /

PRCA 80 /

JC PML PML PML PML BK BK BK 3g 2.0% 2.8% 3.6% 0.5 103/ ANC 3 /ml <1.3 10 31 180 PRCA PRCA PRCA /

/ IM - HGPRT - Kelley- Seegmiller 1 g bid 5 ml 2.78 mg

3 4 6 D FDA 0.02~0.9 25 mlu/ml 8~10 /

6 90 90 / 23~27% 2 % 4~5% 45~49% 12~33% /

600 mg/m 2 bid 1 g bid 65 PPI MPA MPA PPI 4 4 g tid 1.5 g MPA AUC 40% A A CsA /

A A MPA MPA 30~50% MPA 30% MPA PPAR UGT1A9 DDI MPAG MPA 18 3 1g bid0.02~ 0.04 mg 0.05~ 0.20 mg 0.15 mg 0.05~ 0.10 mg LH FSH MPA AUC 0~12h 70% MPA MPA AUC C max 1.5 g AUC 20% β- MPAG/MPA MPA /

MPA 54% MPA MPA AUC 0-48 30% MPA / / MPA AUC C max MPAG AUC 3 MPAG MPAG MPA C max AUC 0~12 30% 25% 2 MAP MPA MPAG 100 μg/ml MPAG MPA /

A 3 1 1 3 2 1 g bid 1.5 g bid A 1 1 14 1 20 1 21 6 1 A/ 3 1. / / A/ 2. / A/3. A/ A/ 6 3 g/d 3 g/d a n=499 2 g/d 3 g/d 1~2 mg/kg/d /

n=167 n=166 n=166 31.1% 31.3% 47.6% 9.6% 12.7% 6.0% b 19.8% 17.5% 38.0% / c n=503 2 g/d n=173 3 g/d n=164 100~150 mg /d n=166 38.2% 34.8% 50.0% 13.9% 15.2% 10.2% 19.7% 15.9% 35.5% n=491 2 g/d n=165 3 g/d n=160 n=166 30.3% 38.8% 56.0% 11.5% 22.5% 7.2% 17.0% 13.8% 46.4% a // A/ b c / A/ d / A/ 12 3 2 g/d 3 g/d 3 2 2 g/d 3 g/d 1 12 2 g/d 3 g/d /

8.5% 11.5% 12.2% / / 11.7% 11.0% 13.6% 8.5% 10.0% 11.5% 9 5 1 100 3 ~ 18 600 mg/ m 2 bid 1 g bid A/ 1 g bid 3 ~ 6 6 ~12 12~18 6 12 5%2% 20 1 5 2 650 72 578 1.5 g bid n=289 1.5~3.0 mg/kg/d n=289 A/ 1. 6 12 6 12 1. 2. 12 97.5 0.9 6 /12 /

N=323 N=327 N=289 N=289 6 121 38% 120 37% 100 35% 92 32% * 12 49 15.2% 42 12.8% 33 11.4% 18 6.2% * 20 mm 25% <2.0 L/min/m 2 25% 30% 60% 25% 3 20% 25% 16 2 4 1 565 1 g bid 14 1.5 g bid 1~2 mg/kg/d 1~2 mg/kg/d A/ 1.5 mg/kg/d 0.3~3.8 mg/kg/d 1 1.26 mg/kg/d 0.3~3.8 mg/kg/d1. 6 2. 12 12 ITT A/ 6 1 6 /12 N=287 6 137 47.7% N=278 107 38.5% /

1 42 14.6% 41 14.7% 9 64 46 130 + + + + + 26.0% + 45.0% 31 0.5~1.0 g 2 / 33 / 1. 0.5~ 1.0 g 2 12 2. 12 1. OKT 3 ATG ALG2. 12 5 9.6% 1 3.6% 4 2 1 1 16.7% 5 4 1 1. 64 5 4.6 2. 4 2 3 4 4 3. 64 24 4. /

MMF MPA 2- MPA IMPDH T B B - 1-2 DNA / 20mg/kg/d 0.1 0.07 4.5mg/kg/d F1 0.02 0.01 F1 104 180mg/kg/ 2g/d 0.5 3g/d 0.3 104 15mg/kg/ 0.08 0.05 MPA MPA MPAG 5 0.4 μg/ml /

12 94% MPA AUC 3 g MPA AUC 1.5 g bid 27 650 MPA AUC MPA C max 40% 12 MPA 3.6 1.5 4.01.2 L/kg97% MPA MPAG 82% MPAG MPAG MPAG MPA MPA 0.6 MPA MPAG MPA 25 mg/dl MPAG460 μg/ml MPA A MPA MPA 100 μg/ml 53% 45% 90% 87% MPA MPA MPA MPAG MPAG MPA 2-N -(2-) - N -(2-) - N N-(2- ) - 6~12 MPA g tid MPA AUC 40% AUC MPA MPA 50% MPAG 3 6 MPA 1% /

93%6% 87% MPAG MPA MPAG MPAG >100 μg/ml MPAG MPA MPA 17.96.5 19348 ml/min 16.65.8 17731 ml/min MPA 40 3~6 MPA AUC 20~41% C max 32~44% 1g 2 bid 5 MPA AUC 24% 1 g bid 1.5 g bid MPA AUC 1 g bid T max h 1g/ 0.80 (±0.36) (n=129) T max h 5 1g/ 6 1g/ 1.58 ( 0.46) (n=31) 1.33 ( 1.05) (n=31) C max μg/ml 24.5 (±9.5) (n=129) C max μg/ml 12.0 ( 3.82) (n=31) 10.7 ( 4.83) (n=31) AUC μg h/ml 63.9 (±16.2) (n=117) AUC 0~12h μg h/ml 40.8 ( 11.4) (n=31) 32.9 ( 15.0) (n=31) /

40 1g/ 40 1.5g/ >3 1.5g/ 1.31 ( 0.76) (n=25) 1.21 ( 0.81) (n=27) 0.90 ( 0.24) (n=23) T max h 1.5g/ >6 1.5g/ 1.8 ( 1.3) (n=11) 1.1 ( 0.7) (n=52) T max h 4~9 1g/ 5 ~8 1.5g/ >6 1.5g/ 1.50 ( 0.517) (n=22) 1.15 ( 0.432) (n=20) 1.54 ( 0.51) (n=6) 8.16 ( 4.50) (n=25) 13.5 ( 8.18) (n=27) 24.1 ( 12.1) (n=23) C max μg/ml 11.5 ( 6.8) (n=11) 20.0 ( 9.4) (n=52) 27.3 ( 10.9) (n=25) 38.4 ( 15.4) (n=27) 65.3 ( 35.4) (n=23) AUC 0~12h μg h/ml 43.3 ( 20.8) (n=9) 54.1 ( 20.4) (n=49) C max μg/ml AUC 0~12h 17.0 ( 12.7) (n=22) 13.1 ( 6.76) (n=20) 19.3 ( 11.7) (n=6) μg h/ml 34.0 ( 17.4) (n=22) 29.2 ( 11.9) (n=20) 49.3 ( 14.8) (n=6) AUC 0~12h 4 2 500 mg 4 250 mg MPA T max C max AUC 0~96h /

h μg/ml μg h/ml GFR>80mL/min/1.73m 2 n=6 1g GFR50~80mL/min/1.73m 2 1g n=6 GFR25~49mL/min/1.73m 2 1g n=6 GFR<25mL/min/1.73m 2 1g n=7 n=6 1g 1g n=18 0.75 ( 0.27) 0.75 ( 0.27) 0.75 ( 0.27) 1.00 ( 0.41) T max h 0.63 ( 0.14) 0.85 ( 0.58) 25.3 ( 7.99) 26.0 ( 3.82) 19.0 ( 13.2) 16.3 ( 10.8) C max μg/m L 24.3 ( 5.73) 22.4 ( 10.1) 45.0 ( 22.6) 59.9 ( 12.9) 52.9 ( 25.5) 78.6 ( 46.4) AUC 0~48h μg h/ml 29.0 ( 5.78) 29.8 ( 10.7) 6 GFR 25ml/min/1.73m 2 MPA AUC GFR>80mL/min/1.73m 2 28 75% MPAG AUC 3~6 MPAG MPAG GFR 25ml/min/1.73m 2 1 g MPA AUC 62.419.3 μg h/ml n=4 MPA AUC 0~12h MPA MPAG AUC 0~12h 2~3 /

8 28 MPAG 6~8 MPA 1~2 MPA MPAG >100μg/mL MPAG 18 6 1g MPA AUC 50% 6 0.2% 1 g MPA MPA AUC 44.115.5 μ h/ml 18 600 mg/m 2 bid 55 1 ~18 MPA MPAG MPA MPA 1~2 6 d a a h 3.03 4.70 C max μg/ml 10.3 5.80 AUC 0~12h μg h/ml 22.5 6.66 1~6 17 1.63 2.85 13.2 7.16 27.4 9.54 7 6~12 16 0.94 0.546 13.1 6.30 33.2 12.1 12~18 21 1.16 0.830 11.7 10.7 26.3 9.14 b 1~2 4 d 0.725 0.276 23.8 13.4 47.4 14.7 1~6 15 0.989 0.511 22.7 10.1 49.7 18.2 3 6~12 14 1.21 0.532 27.8 14.3 61.9 19.6 c 12~18 17 0.978 0.484 17.9 9.57 53.6 20.3 1~2 4 d 9 0.604 0.208 25.6 4.25 55.8 11.6 1~6 12 0.869 0.479 30.4 9.16 61.0 10.7 /

6~12 11 12~18 14 1.12 0.462 29.2 12.6 1.09 0.518 18.1 7.29 66.8 21.2 56.7 14.0 a 600 mg/m 2 b n=20 c n=16 d 1~6 600 mg/m 2 bid 1 g bid MPA AUC 1 g bid MPA AUC >3 45%~53% 1~18 MPA AUC MPA 1 g/m 2 MPA AUC 1~12h 32.0 14.5 n=79 36.5 18.8 μg h/ml n=4 MPA C max 9.96 6.19 10.6 5.64 μg/ml 15~30 20 / 50 / 36 /

YBH08952003-2014Z 2015 H20031277 1100 201203 021-28922888 021-50801800 http://www.roche.com.cn CellCept http://www.roche.com.cn 800-820-8780 400-820-8780 9:00-18:00 /