Your SlideShare is downloading. ×

Japanese

473

Published on

pharmasui

pharmasui

0 Comments
0 Likes
Statistics
Notes
  • Be the first to comment

  • Be the first to like this

No Downloads
Views
Total Views
473
On Slideshare
0
From Embeds
0
Number of Embeds
0
Actions
Shares
0
Downloads
7
Comments
0
Likes
0
Embeds 0
No embeds

Report content
Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel
No notes for slide

Transcript

  • 1. 2010 11 42010 1 3 871139 2 mg 22000AMX02362 5 mg 22000AMX02363 25mg 22000AMX02364 100mg 22000AMX02365 2008 12 1990 11 1 100 200mg 2 1 1 2 1 50mg 1 2 1 100mg 2 1 2 100mg 1 200 400mg 2 2 2 2 mg 2 mg 5 mg 25mg 100mg 5 mg 25mg 100mg 1 1 1 1 2 1 0.15mg 2 mg 5 mg 25mg 100mg kg 1 2 1 0.3mg kg 1 1 2 0.3mg kg 1 1 1 5 mg kg 1 1 1 3 mg kg 2 1 200mg mm mg 1 1 LTG 2 40 2 1 0.6mg 2 mg kg 2 2 1 1.2mg kg 2 GS CL2 101 5 mg 1 2 1.2mg kg 1 5 15mg kg 2 GS CL5 63 1 400mg 25mg 2 2 GS CL7 253 1 100mg 2 1 Lennox Gastaut 2 25mg 100mg 2 1 25mg 2 1 25mg 1 1 2 25 50mg 1
  • 2. 2 43 UGT1A4 2 5 350 2 65 1704 1 2 1 1 2 mg 2 mg 1 1 1 mg 2 65612 1 13 31 8 2 2 FSH LH2 83 2
  • 3. 335 185 55.2 62 18.5 51 15.2 26 7.8 21 6.3 18 5.4 149 65 43.6 19 12.8 12 8.1 11 7.4 212 107 50.5 47 22.2 21 9.9 12 5.7 11 5.2 1 92 36 39.1 14 15.2 5 5.4 11 1 2000 1 2 2 3 5 3 4 2 5 3 1 502 2 10 20 3
  • 4. 1 25 200mg 1 PTP PTP Cmax Tmax t1 2 AUC0 CLt F Vd F n PTP mg μg mL hr hr μg hr mL mL min L 25 6 0.338 0.031 1.7 0.8 37.9 11.1 15.2 4.9 29.77 9.12 91.0 8.1 50 6 0.718 0.049 2.5 1.2 35.0 4.7 33.7 5.9 25.33 4.09 75.2 4.8 100 6 1.488 0.261 2.3 1.4 30.5 3.3 59.9 12.1 28.79 5.65 74.2 9.2 200 6 3.075 0.336 2.5 1.0 32.4 5.5 136.1 33.2 25.64 5.69 69.8 9.3 2 2 8 2 200mg 9.6μg mL 2.2μg mL 3 1 2 199 mg b μg mL 2 0.43 0.24 3.25 100 200 5 10 1.44 9.58 1000 2.81 200 400 60 99 1.9 95 0.6 3.9 0.32 7.28 c a b 1000 2.4 c 1 2 3 mg b μg mL kg 3695 43 1.16 3.85 1 3 18 45 2824 25 0.89 1.07 11.38 2.32 1 5 48 101 0.29 5.91 3.30 5 15 30 54 0.70 9.82 1073 6 0.56 a 805 2 0.25 b 3 1 2 13 1 2 70 3 1 8 75mg 97.6 4 5 12 150mg Tmax AUC 53 1 56 2 in vitro 1 10μg mL 141 6 C 6 25 200mg 1.7 2.5 240mg 15μCi 168 2 Cmax t1 2 31 38 Cmax AUC0 94 N2 71 6 50mg 1 2 10 10 N5 5 10 6 N2 0 14 9 10 UGT1A4 14 C N2 17 29 11 12 13mL min 6 854μmol L 100mg t1 2 16 22 AUC 18 4 20 12 12 24 100mg Cmax Cmax Tmax AUC0 1 25 200mg t1 2 2 4 CL F 2 3 1 3 4
  • 5. 4 1 Add on n 12 n 12 n 7 n 5 Child Pugh A B C 150mg 20 300mg Cmax 1 61 1 34 1 48 1 65 μg mL 1 14 2 53 0 99 1 81 1 22 2 26 1 12 1 84 Tmax 1 00 1 00 1 00 2 00 hr 1 00 8 00 1 00 4 00 1 00 4 00 1 00 9 52 Wilcoxon t1 2 32 16 35 99 59 68 110 13 hr 22 27 49 29 30 16 89 08 34 79 145 12 50 11 158 14 10 20 16 26 12 3 87 AUC0 69 07 70 60 110 72 248 86 11 23 18 30 14 3 p 0 0119 μg hr mL 38 77 98 09 47 86 215 75 73 53 225 35 73 72 368 62 8 13 9 34 23 2 89 CL F 0 338 0 312 0 237 0 103 9 15 10 38 26 2 mL min kg 0 267 0 593 0 165 0 443 0 114 0 356 0 061 0 260 12 65 61mL min 150mg Cmax AUC0 t1 2 CL F 66 6 17 9 22 10 2 23 35 2 35 0 40 μg mL 93 8 21 0 μg hr mL 31 2 5 4 0 396 0 063 mL min kg 66 6 12 7 20 20 1 18 27 13 150mg 7 0 3 2 1 1 0 3 43 Cmax AUC0 t1 2 CL F 2 45 0 18 μg mL 117 30 24 61 11 1 1 1 7 1 0 2 18 μg hr mL 31 2 6 4 0 313 0 087 mL min kg Lennox Gastaut 11 1 3 3 2 2 0 4 36 16 1 0 1 10 4 0 1 61 2 Add on 1 500mg 1 2 50mg 100mg 150mg 1 5 mg kg 1 1 1 3 mg kg 5 15mg kg t1 2 2 CLt F 1 2 21 5 Wilcoxon Cmax Cmin Tmax t1 2 AUCss CLt F Vd F n 12 26 18 18 9 3 μg mL μg mL hrhr μg hr mL mL min kg L kg 8650mg 3 45 0 61 2 53 0 46 1 83 0 98 75 3 14 1 66 7 10 9 0 17 0 03 0 94 0 10 14 30 21 21 10 3 p 0 0009100mg 18 6 78 1 13 5 02 0 97 1 96 1 00 69 6 14 3 132 5 22 6 0 17 0 04 0 88 0 09 3 17 17 22 20 3 82 4 21 21 27 24 4150mg 9 44 1 71 6 48 1 52 2 02 0 96 69 6 14 8 178 2 37 1 0 20 0 05 1 03 0 18 2 600mg 1 1 5 25mg t1 2 5 13L 33 5 7 7 9 5 0 12 36 hr 14 1 5 25mg 39 3 11 9 8 6 2 14 36 t1 2 2 6L hr 23 8 17 3 9 1 2 1 1 12 71 12 0 1 3 4 4 0 1 8 14 t1 2 33 3 11 8 6 4 1 14 42 Lennox Gastaut 3 34 0 5 6 11 12 0 5 15 15 3 50 1 4 100mg 300mg 10 4 18 173 100mg 3 AUC Cmax 100mg 16 32 6 29 3 102 5 400mg 2 mg 102 3 29 2 mg 14 12 20 1 173 18 10 4 6 30μg 150μg 2 Stevens Johnson 300mg AUC0 24 Cmax 48 61 547 3 05 Stevens Johnson 7 2 335 1 03 212 2 AUC0 24 Cmax 09 81 88 AUC0 24 93 Cmax 22 23 1 Add on 7 400mg 200mg 1 1 15mg 1 1 56 AUC0 24 Cmax 300mg 150mg 76 80 AUC0 24 Cmax 8 1 150 500mg 200 400mg 35 17 400mg 88 25 9 2 34 150mg 300mg 41 26 1 2 18 p 0 00110 24 2 Add on 400mg 5 mg kg 250mg 19 AUC Cmin Cmax 15mg kg 750mg11 400mg 1 2 5 25mg 5 25mg 14 98 3612 100mg 1 1 2g 1 2 6 101 7 p 0 012 In vitro OCT2 5
  • 6. 3 Lennox Gastaut 3 25 Add on 25 1 Newport D J et al Pediatrics e223 231 2008 5 mg kg 200mg 2 Wolf P et al J Epilepsy 73 79 1992 15mg kg 400mg 3 Yuen A W C et al Br J Clin Pharmacol 511 513 1992 4 Binnie C D et al Epilepsia 248 254 1986 5 Jawad S et al Epilepsy Res 194 201 1987 6 Anderson G D et al Clin Pharmacol Ther 145 156 1996 78 32 7 Morris R G et al Br J Clin Pharmacol 547 551 1998 89 9 8 Yuen W C et al Br J Clin Pharmacol 242P 1988 9 Magdalou J et al J Pharmacol Exp Ther 1166 1173 1992 p 0.05 26 10 Green M D et al Drug Metab Dispos 299 19954 2 55 Add on 11 Fillastre J P et al Drugs Exp Clin Res 25 32 1993 2 12 3 mg kg 200mg 12 Marcellin P et al Br J Clin Pharmacol 410 414 2001 12 200mg 2 12 12mg 13 Posner J et al J Pharm Med 121 128 1991 kg 400mg 12 400mg 14 Ebert U et al Eur J Clin Pharmacol 299 304 2000 15 van der Lee M J et al Clin Pharmacol Ther 159 168 2006 16 Burger DM et al Clin Pharmacol Ther 698 703 2008 17 Levy R H et al Ther Drug Monit 193 198 2005 58 82 18 Weintraub D et al Arch Neurol 1432 1436 2005 59 43 19 Doose D R et al Epilepsia 917 922 2003 p 0.006 20 117 134 20085 21 425 440 2008 Add on 8 22 Messenheimer J A et al Epilepsia 113 121 1994 23 Schapel G J et al J Neurol Neurosurg Psychiatry 448 453 1993 24 Duchowny M et al Neurology 1724 1731 1999 25 Motte J et al N Engl J Med 1807 1812 1997 26 Biton V et al Neurology 1737 1743 2005 27 Matsuo F et al Neurology 2284 2291 1993 0 16 0 30 0 46 0 0 0 28 Schachter S C et al J Epilepsy 201 209 1995 26 0 8 0 4 0 12 29 Sander J W A S et al Epilepsy Res 221 226 1990 0 0 0 30 Miller A A et al Epilepsia 483 489 1986 0 27 4 605 4 632 31 Cramer C L et al Life Sci PL271 275 1994 0 07 06 32 Dalby N O et al Epilepsy Res 63 72 1997 22 25 27 29 3 95 2 82 5 177 33 Wheatley P L et al Epilepsia 34 40 1989 32 24 28 34 Otsuki K et al Epilepsy Res 101 112 1998 0 43 4 635 4 678 35 Stratton S C et al Epilepsy Res 95 106 2003 0 06 06 36 De Sarro G et al Neuropharmacology 153 158 1996 3 103 2 86 5 189 37 Smith S E et al Epilepsy Res 101 111 1993 29 23 26 38 Hosford D A et al Epilepsia 408 414 1997 39 Xie X et al Pflügers Arch 437 446 1995 40 Leach M J et al Epilepsia 490 497 1986 30 1 151 8566 4 6 15 2 4 6 7 dimethoxy 4 ethyl β carboline 30 32 3 carboxylate DMCM 33 TEL 0120 561 007 9 00 18 00 3 FAX 0120 561 047 24 4 34 35 35 5 EL lethargic 36 38 6 ED50 37 ED50 Na 39 40 Lamotrigine 3 5 Diamino 6 2 3 dichlorophenyl 1 2 4 triazine C9H7Cl2N5 256.09 N Cl N Cl H2N N NH2 logP 0 4 pH1 2 1 8 0 pH6 0 1 2 mg 140 14 10 PTP 5 mg 140 14 10 PTP 25mg 140 14 10 PTP 100mg 140 14 10 PTP A 21 25mg B 84 25mg 6

×