ビデュリオン皮下注用2mg インタビューフォーム
Contents
1. 99 STEP32. 100 STEP 4 a occ 2 3 Cm
3. 60 61 62 60
4. 2 3cm 28 29 ML EF 1
5. CWCK 2 2 2 0 mg 2 0 mg 40 84 BMTI 145 188 U L 27 6 148 CT
6. gt 1 101 4 30C 3
7. gt 25
8. IF IF IF A4 9 IF IF
9. 2 GWBX GWCK 2 2 mg 1 gt WBW GWBX GWCK
10. 1 2 8 2 3 12 8 2 3 13
11. Pediatric se 2012 1 Safety and effectiveness of BYDUREON have not been established in pediatric patients BYDUREON is not recommended for use in pediatric patients 2011 5 Paediatric population The safety and efficacy of BYDUREON in children and adolescents aged under 18 years have not yet been established see section 5 2 No data are available 110 XTE 111 BD 13 02 0009 15 01 IF410
12. SGCSGSSGGGSS OES OCSGGCGCSSSSSSc 65555 CI TIT TTT 9 00 22 00 01820 189 550 97 SE lt 3
13. 4 w
14. 60 5ngX2 J 1 10ngx2 22 30 82 44 45 47 48 49 5 ngx2 1 10 ngx2 130 gt 140 2 INR 6 7 HDb 7 1 g dL
15. 98 STEP 3 STEP
16. 2 3 4 GWBX CWCK ICSD BCB108 8 Tntegrated Completed Studies Database 5 4 DPP 4 1 GLP 1 6
17. HbA 7 32 2 0 8 mg 2 0 mg 1 15 LAR 104 2 0 mg 1 1 2 1 2 30 LAR 105 625 C 25 C 125 C 16 89 6
18. Fine needle aspiration 4 GWBX WCK CCDS Company Core Data Sheet 5
19. 0 2 5ugX2 5 ngx2 HbAi 9 20 1 10 ngx2 BMI 40 1 8 HbAi 7 2 0 80 10ngx2 mg7dL 5 4 13 5 mg dL 38 9 mmolL K 5 2 mmolL pH7 3 150 mg dL 5 12 Na 140 mmolL Na 84 mmolL 21 mmol L RFNA 4 2 ATN I
20. 17 1 2 8 1 2 3
21. 12 13 w 59 4 14 15 16
22. 0 0 2 22 156 260 22 ng kg NZW BID 20 6 18 0 2 229 0 2 1582 3841 0 2 22 260 NZW BID 20 6 18 2 8 13 229 PF 8841
23. 63 2 IF IF 10 9 3 IF 10 20 9 IF 2 IF IF
24. Q7 A7 Ns STEP3 Q8 A8 STEP4 Q9 A9 Reo 9 00 22
25. 2 3cm 3cm STEP 1 1 2 a
26. MAO 8 56 57 58 MAO MAO 59 66
27. 2012 3 30 2018 10 26 103 15 1 1 14 16 1 2mg 2499411G3029 2 HOT 2mg 1222906010101 3 2mg 622229001 17 104 Xi 1 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 Iwamoto K et al Endocr J 56 8 951 962 2009 030 307706 DMA9 0001 Inagaki N Clin Ther 34 9 1892 1908 2012 030 307825 DMB2 0001
28. 4 5 3 4 6 7
29. 3 0 29 4 5
30. 70 mg dL 29 2 V 3 5 1 GWBX GWCK 3 1 2 gt GWAB 17 1 2 10 ng 5 10 ng 5 ng tj 1 45 2
31. 2 2 678 340 1 2 338 155 22 996 78 1 2 77 1 2 2 Visit 1 90 SU BG TZD SU BG SU TZD BG TZD 3 HbAi 7 19 11 096 4 BMTI 21 kg m2 35 kg m2 5 20 6 Visit 1 90 5 Visit 1 6
32. IF 3 IF 2008 MR PDF IT MR IF IF IF MR IF
33. Phase 1 Phase 2 Phase 3 2 Phase 2 Phase 3 200 iPhase 11 Phase2 Phase3 2 5 mg N 11 vy 5mg N 9 4 7mg N 11 10mg N 10 pg mL 40 2 5 mg 5 0 mg 7 0 mg 10 0 mg 2
34. CrCL gt 80 mL min 8 C CL 50 80 mL min 8 C CL 830 50 mL min 6 C CL 30 mL min 8 5 10 ng ts 1 45 2 12 3 16 5 95 tiz 17 2 CrCL gt 50 mL min 183 86 84 17 3 V 4 V 57 5
35. 2 2 3 2 STEP1 STEP3 E STEP3
36. 3 8 5 2 10 11
37. 8 DPP 4 Dipeptidyl Peptidase 4 ZZ9Z gt GLP 1 GIP b 2 Ala Gly DPP IV GLP 1 Human TN DPP_V 2 31 1 PLG 1 GLP 1 ZZ ztro 20 GLP 1 GLP 1 25TIIGLP 1 GLP 1 25TIGLP 1
38. 311 mg dL O 2 272 mg dL 504 mg dL 3 520 mg7 dL 4 C 0 2ng mL 5 126 mg dL 1 5 HbA 3 gt 4 WCK
39. 1 2
40. 7 4 8 GWBX GWCK CCDS Company Core Data Sheet CCDS GWBX 11 2 24 GWCK
41. 2012 11 2 1 1 2 2 1 HbAic 3 818 556 426 52 196 161 19 79 104 12 796 62 7 696 55 6 79 6 49 6 0 43 5 89 70 II
42. 4 DPP 4 1 GLP 1 75 3 596 1 596 196
43. Tel 0120 189 113 Fax 06 6433 7376 MediChannel http med astrazeneca co jp Tel 0120 093 307 Fax 03 6705 7934 http www bms co jp medicalindex html IF 2013 5 2 http www info pmda go jp IF 1
44. 1 0 0 12 1 0 1 0 12 82 22 104 12 71 3 0 3 0 37 0 1 1 0 12 1 0 1 0 12 2 0 2 0 24 1 0 1 0 12 4 1 5 0 61 0 1 1 0 12 1 0 1 0 12 0 6 6 0 73 1 0 1 0 12 1 0 1 0 12 2 0 2 0 24 1 0 1 0 12 2 0 2 0 24 27 16 43 5 26 0 1 1 0 12 1 0 1 0 12 0 6 6 0 73 5 1 6 0 73 0 4 4 0 49 0 1 1 0 12 32 10 42 5 13 1 2 3 0 37 1 0 1 0 12 12 1 13 1 59 1 0 1 0 12 6 1 7 0 86 1 0 1 0 12 1 0 1 0 12 1 0 1 0 12 1 0 1 0 12 1 4 5 0 61 16 1 17 2 08 1 0 1 0 12 7 7 14 1 71 2 0 2 0 24 45 4 49 5 99 1 0 1 0 12
45. 2 2 mg 1 10 3 4 50 pg mL 8 2 2 mg 1 26 8 50 350 pg mL 1 2 GWBX GWCK 2 2 mg 1 1 2
46. 38 mg kg min 15 2 UNS 8 n 12 5 6 6 7 5 3 5 0 1 10 100 1 000 10 000 gg ZDF 1 10 100 1000 3000 9000 ng 60 180 n 12 5 6 6 7 5 3 5 7 o 26 27 Zucker fatty fa fa 9 1 2 6 ng kg day 6 24 Pair Teed 8
47. 1 2 3 4 5 6 7 8 9 6 2 10 4 90 11 90 DPP 4 23 2 0mg 1
48. 2 mg 1 42 2 9 2 11 1 2 5 ng 1 3 14 2 5 mg 8 Phase 1 10 12 pg mL 60 pg mL 0 6 12 18 24 2 2 5 mg 24 120 100 80 60 20 2 2 5 mg 12
49. 3 30 HMG CoA W 7 50 3 15 25 mg 1 2 10 ng tmax 2 AUC Caa INR VI 7 36 5 20 mg 22 1 2
50. 9 1 47 58 48 2 49 50 3 51 52
51. K 1 5 INR 3 1 9 3 gdL 2 137 199 66 mmHg 7 3 3 4 Hb HCT
52. 34 6 pg mL GWAB 8 Lh 95 p CrCL gt 80 mL min 1 CrCL OO 12 7 11 0 69 1 11 0 2581 mL min CrCL 30 50 6 5 19 0 46 0 89 0 0083 mL min 0 16 3 9 0 12 0 22 OO 1 GWAB 5 18 1 2 gt 2 15 75 85 CrCL 30 80 mL min 5 10 ng C AUOCo 2 15 45 65 CrCL gt 50 mL min 12 419
53. 10 1 22 ng kg 2 mg 1 1 49 5 68 ng kg 2 mg 1 1 5 4 0 3 mg kg 2 mg 1 1 1 7 3 1 3 mg kg 2 mg 1 1
54. 459 59 1 18 70 250 ug kg 2 9 6 7 22 7 1 2 5 6 30 8 2 1 1 250 ng kg C C C C
55. 6 W 8 2 9 1 2 2 GWCC 15 75 85 C CL 80 80 mL min 5 10 ng Cmax AUCo 15 45 65 CrCL gt 50 mL min 12 41 18
56. CWCK 1 2 i OR GGWCK N 340 n n n n 76 35 3 1 0 5 35 10 3 1 0 3 14 6 5 1 0 5 19 5 6 1 0 3 GWBX 78 20 15 9 GWCK I 1 2 1 83 Co Ca Ky SR 2 SR 2 LC Ce Es gt 8 12 gt 12 16 gt 16 20
57. 86 1 1 a EE ba 2 TSH 1 24 pIU mL FT4 1 4 60 5ugX2 2 ng dL TgAb 0 3 U mL CA19 9 19U mL BMI CEA 2 0 ng7mL 27 7 1 5 ngx2 10 24 pg mL pgx2 10 28 1 10 ng 6 100 PTH 49 9 pg mL 23 pgmL 46 7 ng mL FT4 1 1 ng7dL FT3 2 7 pg mL TSH 2 0 1 0 IU L TPO 0 3 U mL mg 149 181
58. 26 2 01 kg 26 p lt 0 001 kg 1 0 0 5 oO 00 05 2 01 9596CI 2 46 1 56 001 _ 1 0 _1 5 6 e 201_ 0 4 8 12 20 26 n 214 213 211 205 203 196 214 n 212 212 210 208 203 212 206 lt 52 52 1 48 kg 26 26 26 38
59. 51 4 53 6 1 3
60. 43 2 2 5 mg n 1 1 2 5 mg 0 48 Cmax pg mL 29 2 5 92 tnax h 9 2 1 0 0 0 8 48 Cmax pg mL 67 2 9 22 tmax day 9 48 1 35 0 61 0 0 AUC pg h mT 40378 4903 C y pg7mL 20 0 2 43 Ca a 2 mg 1 3 10 gt Il 2 14 625 0 8 mg 2 0 mg 1 10 0 8 mg 2 0 mg 1 8 8
61. 5 n 215 n 212 8 51 0 06 8 50 0 06 0 2 1 0 68 0 8 SU YIM 2 p lt 0 001 1 4 p lt 0 001 t VS 26 HbAi 52 HbAi 52 30 38 HbAi 52 52 HbAi 1 0296 0 979 1 069 1 07 38 HbAi
62. WBX Full Analysis Set 77 1 2 EE 1 1 0 4 gt 4 8 gt 8 12 gt 12 16 gt 1620 gt 20 24 gt 24 2 GWCK Intent To Treat 0 Ss PLG 66 PLG GWBX WCK
63. 1 63 kg p lt 0 001 1 2 2 45 kg p lt 0 001 26 1 2 0 82 kg 1 2 p lt 0 001 26 20 0 82 0 22 lt 0 001 0 4 12 20 26 ns337 330 321 311 311 309 n 333 329 312 289 281 265 52 26 0 50 kg 1 2 1 65 kg 52 1 42 kg 0 91 kg 26
64. FDA Pregnancy Category C 2012 1 An Australian categorisation of risk of drug use in C 2012 11 Dregnancy FDA Pregnancy Category C Animal reproduction studnes have shown an adverse effect on the fetus and there are no adeguate and well controlled studies in humans but potential benefits may warrant use of the drug in pregnant women despite potential risks An Australian categorisation of risk of drug use in pregnancy C Drugs which owing to their pharmacological effects have caused or may be suspected of causing harmful effects on the human fetus or neonate without causing malformations These effects may be reversible Accompanying texts should be consulted for further detals
65. 26 48 61 mg dL p lt 0 001 1 2 49 49 mg dL p lt 0 001 1 ns 338 n 337 26 26 6 27 26 9 41 mg qL p lt 0 001 1 2 8 10 mg dL p lt 0 001 LDL HDL 26 336 206 336 45 13 496
66. 9 1 31 1 2 23 7 80 WCK 76 1 2 1 15 5 Rd 1 1 om 1 Rd od a Pe lt po 5 0 EB EE PRS S82 gt 12 16 gt 1620 20 24 GWCK Intent To Treat GWBX
67. A B C mg pancreas 115 2 8 1 n 6 Pair Feed 188 9 27 1 n 5 181 4 24 4 n 5 a 8 1 1750 109 n 6 Pair Feed 0 764 0 126 n 5 0 520 0 100 n 5 Pair Feed c Pair Feed D
68. w 4 DPP 4 14 8 2 1 15 15 2 16 26 GWBX 4 46
69. AUC 49 6 1 2 49 AUO 20 t 1 2 AUCosm Cmax tmax 2 tnax h PS 0 14 90 CI 90 C1l 0 96 0 84 0 98 1 4 26 0 84 1 10 0 72 0 99 0 25 8 0 0 25 8 0 2 0 96 0 95 0 90 1 3 8 0 84 1 09 0 81 1 11 0 25 3 4 0 25 5 2 1 2 9 0 80 0 79 0 87 2 0 0 70 0 921 0 66 0 93 0 25 1 8 0 25 5 2 AUC
70. 2mg 1 2 6mg 1 2mg pH 5 8 7 2 1 2 2 1 2mg 1 2 6 mg 2mg 650 50 48 4 mg 1 1 0 mg 3 4 0 75mL 23 mg 5 0 mg RT
71. AUC Cmax tmax 30 ng 150 ng 6 39 2 LAR 104 LAR 105 625 CrCL BMI G CrCL CrCL C C 25
72. 1 GLP 1 glucagon like peptide 1 GLP 1 7 36 amide 539 GLP 1 2 2 2005 4 1 2 2010 10 2012 3 90 1 PLG 1
73. IF 2008 9 1 1 1 2 i 2 I Ek 3 ES 3 RE 3 3 3 4 3 5 J Gk 4 6 un 4 AS 4 5 1 i 5 2 6 3 A 6 4 6 WV LL 7 29RD 0 P7900 0 7 2 Ei 7 3 EANMMAMN 8 4 8 5 9 6 9 7 9 8 9 9
74. 182 29 pg mL 44 4 ng mL FT4 1 0 ng dL FT3 2 5 pgmL TgAb 0 83 U mL TPO 0 3 U mL 192 148 8 5 mm 197 217 ClassIb Papillary Carcinoma suspect 366 TNM pT4aN0Mx 450 87 2
75. 26 46 09 mg dL p lt 0 001 40 82 mg dL p lt 0 001 26 5 28 mg 7dL 52 52 43 09 mg dL 43 77 mg dL 26 26 1 67 kg p lt 0 001 0 34 kg p 0 044
76. 2 0 2 2 Ins 30 Tns 7 BMI 4 Ins Ins 4 1 1 30 7 1 16 16 Ins 6 6 96 Ins 7 141 141 Ins 8 8 182 Ins 1 184 182 315 Ins Papillary Careinoma l 7 184 95
77. 0 8 1 0 3 0 mg kg 2 1 C 1 0 mg 3 0 mg kg C 69 GWBX GWCK 3 GLP 1 3 1 2 3 GLP 1 C 2 2 3 1 2
78. 2 2 2 0 mg 1 1 2 10 ng 1 2 340 338 HbAi 4 12 61 1 t 1 2 HEAT1n ib MCP 1 4 1 20 PmL HER TH N 1 GWCK
79. Ht HbAie 7 0 6 5 26 26 HbAi 7 09 21 09 42 296 p lt 0 001 HbAi 6 59 6 4 296 20 69 p lt 0 001 52 52 HbAi 7 096 6 596 40 8 18 19 26 52 HbAi 7 09 6 59 43 4 22 09 26 HbAi 26
80. 0 40 0 28 0 8 mg 0 99 0 67 2 0 mg 1 48 0 72 10 HbAi HbAi 6 3 10 20 OOO ns me 2Dme 10 20 HbAi lt gt 60 0 6 10 0 8 mg 90 0 9 10 2 0 mg 88 9 8 9 20 0 2 10 0 8 mg 40 0 4710 2 0 mg 44 4 4 9 2 mg 1 4
81. 1 2 GWAG AUC 40 Cmax 28 tmax 4 34 HMG CoA 2 HMG CoA 69 8 1 818 556 426 52 1 161 19 7 104
82. 11 gt 100 99 5 lt 0 1 2 lt 0 1 10 gt 100 pH 3 0 152 pH 4 5 161 pH 6 5 163 pH 8 0 182 2 1 HI 0 mi HH rr 120 lux hr i NN 200W hr m 2 3 4 V 1 Q
83. 845 2 0 mg 346 1 355 346 386 4 3 3 ts 3 2 Ins Ins 4 30 Ins BMI 4 15 Ins 6 33 3 22 Ins 8 15 6 1g1 Ins 183 359
84. C 2 0 mg og mL 2 a 2 0 95 106 9 261 9 308 1 393 3 1562 9 25 97 98 7 274 9 329 4 428 6 1642 0 125 69 123 5 300 5 360 0 519 0 1294 9 625 HbAi HbAi HbAi C s 300 pg mL HDbAi 8
85. 1 1 1379 1 134 2 pmolL 1 2 3100 5 pmolL 5000 4000 3000 2000 1000 E925 9 pmolL 688 5 8 C p lt 0 02 P lt 0 004 n 6 QD BID n 3 n 3 QD 1 1 BID 1 2 8 C 8 30 150 C ZDF C E80 1 pmolL C 500 400 300 200 n 5 8 30 150
86. 1 2 gt 41 2 1 2 10ng CLss F 10 1 L h 31 8 6 1 2 gt 41 2 1 2 10ng 19 1 L 3 1 VI 2 3 3 53 4 Q 2 3 gt 42 21 210ng 210
87. A mgdL B GLP 1 20 100 0 ee 0 100 e e 1 200 0 951 40 400 T TITITITT_TTTTTITT_TTTTTITT_TTTTTTTT TTTTTTTT _TTTTTTTI TTTTTTTT T T T T T T Zero 0 001 0 01 0 1 1 10 100 1000 0 100 200 300 400 500 a 9d ob ob A ob ob n 62 0 001 0 01 0 1 1 10 ng 10 6 6 9 14 0 1 1 10 100 1000 ng GLP 1 n 8 11 11 8 4 9 B 1 ng n 9 34 ZZ ztro 23
88. GWCK 1 2 1 4 mg 1 14 1 1 2 2 1 2 84
89. GWCK SU n 264 76 340 59 22 3 4 5 3 63 18 5 4 DPP 4 SU 64 71 2 1 2 65
90. 2 596 44 5 54 5 1 gt GLP 1 4 ro 21 22 22 28 4 1 21 22 39 1 22 28 89 45 46 CYP450 3 4 Na 5 6 1
91. 47 6 10 2 1 BCB106 26 14 2 0 mg 1 12 12 HbAi 116 232 74 pg mL 220 23 pg mL 205 52 pg mL 12 909 1 01 0 79 1 29 0 98 0 78 1 18
92. n 5 6 ISL Insulin Sensitivity Index vs Pair Feed Student s t test D 8 D deposition index D D p lt 0 05 vs p lt 0 05 40 7 wzvo 28 ZDF 8 1 ng 1 1 2 8 C C
93. C 125 C 105 g 1 kg 105 g 1 kg C HbAi 52 2 1 3 40 1 2 1 2 0 mg AUC 259 5
94. Day 1 Cmax 0 8 mg 64 3 pg mL 2 0 mg 187 pg mL 9 10 Cs 0 8 mg 81 2 pg mL 2 0 mg 345 pg mL 9 10 C AUCweeks to 1o 0 8 mg 141 pg mL 13900 pg h mL 2 0 mg 582 pg mL 60800 pg h mL o pgmL 0 8mg n 8 2 2 0mg n 6 oo 400 200 T T T T T T 0 2 4 6 8 10 12 14 16 18 2 0 8 mg 2 0 mg 10 44 2 0 8 mg 2 0 mg 10 0 8m
95. 1 2 35 79 46 79 p 0 003 HbAi 6 59 1 2 15 59 26 09 p lt 0 001 52 26 HbAi 7 096 41 99 1 2 35 59 6 596 14 99 1 2 17 79 52 HbAi 7 09 45 296 43 29 HbAc 6 59 21 09 6 24 39 52 HbAi 7 09 6 59 26 26
96. IF IF 4 IF IF
97. 26 HbA HbA p lt 0 001 gt 26 3 TEAE Treatment emergent adverse event 58 69 126 215 15 6 33 212 TEAE 34 9 75 11 296 24 7 096 15 6 5 14 6 596 14 5 69 12 9 89 6 21 215 20 89 44 212 52 4 TEAE 20 796 40 193 59 29
98. 26 67 09 mg dL 52 56 mg dL n 215 n 212 2G 26 7 MA re wo 120 120 4 4 0 2 2 2 2 2 2 p lt 0 001 t ves p lt 0 001 vs p lt 0 001 Vs 7 26 14 21 mg dL 6 32 mg dL 7 89 mg dL
99. 63 67 tmax 2 INR 1 2 WAC tmax 2 INR 35 INR 2
100. NIH Swiss 3 4 HbAie D 15 0 38 2 1 pg 04 6 40 250 ng kg day 3 a 90 2 1 ng kg ei a 2 TCR 0 30 300 1 500 gt 300 ng kg 10 gt 1 500 gt 30 ng kg SD 30 300 3 000 3 000 ng kg 5 5 gt 3 000
101. 26 HbAi 52 HbAi HbAi 7 0 6 596 8 7 1 5 1 5 AG gt HbA 26 26 HbAi 1 119 0 06 0 68 0 06 HbA 0 439 95 0 59 0 269 95 0 49 HbA
102. 3 1 GWBW 5 1 GWBX 2 3 4 BG 2 BG TZD 2 2 0 mg 1 26 HbAi 2 215 212 1 2 2 Visit 1 90 BG BG TZD BG SU BG TZD SU 3 HbAic 7 1 11 0 4 20
103. gt 46 55 7 56 1 1 2 1 3
104. p lt 0 001 340 26 59 264 22 39 6 4776 5 396 3 1 GWBW 1 2 1 0 8 mg 2 0 mg 1 10 I 2 30 1 2 Visit 1 60 3 20 75
105. 2 GWBX GWCK HbAi NGSP HbAi JDS 1 GWBX 2 2 2 427 215 212 2 0 mg 1 1 1 26 HbAi HbAi 1 11 0 06 0 689 0 06 HbAi 0 439 6 0 089 95 0 5996 0 269 959 0 49
106. 22 8 436 7 5 455 181 Ins 472 ii 183 2 0 mg 359 88 2 2 3 GWBX 26 213 145 27 12 796 118 55 496 213 68 31 996 GWCK 26 336 206
107. Pair Feed 135 413 7 n 6 Pair Feed 102 8 8 1 n 5 94 8 17 1 n 5 39 Pair Feed 6ug kg a b mgiparc reas EN OF 200 1 1 0 9 100 fF 9 5 0 0 0 a PalrFeed f ih i Par Feedf c d 1 mgipanc reas i RR e388 PairF edt 9 200 8 ioo 3 er a 100 i D sg ol Oo 0 0 5 1 0 1 5 9 068 Pair Feedf Cy2 a 8 b c d
108. 2 mg 1 1 3 GWBW hl I 2 10 0 8 2 0 mg GWBX 2 2 3 4 1 26 52 427 GWCK 5 e 7 g 1 2 1 2 26 52
109. GWBW 2 mg 1 62 8 2 0 8 mg 2 0 mg 1 10 pgimL 0 8mg n 8 2 2 0mg n 6 1000 H 8 3 5 0 2 4 6 8 10 12 14 16 18 0 8 mg 2 0 mg 1 10 GWBW 2 mg 1
110. 030 308035 Kothare P A et al J Clin Pharmacol 45 9 1032 1037 2005 030 307712 DMA5 0005 Kothare P A et al BMC Clin Pharmacol 12 8 doi 10 1186 1472 6904 12 8 2012 030 307936 DMB2 0002 030 308038 030 308036 030 308037 030 308034 Hiles R A et al Hum Exp Toxicol22 12 623 628 2003 030 307742 DMA3 0001 030 308025 in vitro 030 308026 Copley K et al Curr Drug Metab 7 4 367 374 2006 030 307960 DMA6 0001 49 653 658 1991 030 308048 DM91 0002 955 956 1995 030 308067 DM95 0002 84 9 1683 1686 1996 030 308051 DM96 0001 139 143 2000 030 308064 DMA0 0001 451 458 1995 030 308066 DM95 0001 55 89 93 1997 030 308050 DM97 0001
111. 1 8 p lt 0 001 t v 1 2 26 HbA1c a 9 E HbA1c 7 0 4 8 12 20 26 30 34 38 46 52 n 74 74 74 74 74 74 74 72 71 71 n 62 62 62 62 62 62 61 61 59 58 58 52 HbAl1c 26 40 57 2 36 mg7dL 1 2 23 90 2 45 mg dL p lt 0 001 26 1 63 0 16 kg 1 2 2 45 0 16 kg 1 2
112. ICR 10 0 30 300 1500 dP dt Macaca fascicularis 8 1 08 30 300 1000 ng kg RR QT Macaca fascicularis 6 6 08 2 2 18 150 ug kg day hERG hERG HEK293 0 3 5 9 91 1 pmol L 1CR 10 05 30 300 1500 ng kg CD 1 20 25 20 25 SD 10 20 10 20 Macaca fascicularis 6 6 760 ng kg day 182 250 ng kg 91 150 ng kg 273
113. 1 2 PLG 1 2 2001 EU 2011 6 2012 1 2012 3 1 2 2012 3 2
114. 10 9 2 1 0 3 1 0 3 0 mg kg 3 1 3 0 mg kg 82
115. ta 2 C AUC 37 23 1 2 tx 2 5 Ca 189 Ci AUC 88 38 30 ug 150 ng 1 2 10 ng 1 30
116. w 4
117. 1 3 4 5 7 1 2 3 4 1
118. 15 163 21 pmol L 282 27 pmolL 90 165 18 pmolL 298 26 pmolL 15 pmel U n 7 pmoL nm n 600 J 3 a i 400 1 8 3 ei 0 4 200 200 1 o 100 J 01 3S0 30 0 30 60 90 60 30 0 30 60 0 p lt 0 01 vs Student s t test ZDF n 7 Zz vo 28 20 SD 0 01 100 mg GLP 1 0 01 100 mg
119. 26 1 67 0 17 kg 0 34 0 17 kg 215 26 21 9 896 2 WCK 5 6 2 2 2 0 mg 1 1 2 10 ng 1 2 1 678 340 1 2 338
120. 11 12 83 13 1 100 ng 10 2 1 2 118 1 100 ng 10 2 3 67 3
121. 25 5 25 11 2013 2 872499 IF 2008 RR 2 gf 2mg BYDUREOUN 1 2 6mg 1 2mg EE 3 JAN Exenatide JAN
122. 26 40 57 mg dL p lt 0 001 1 2 23 90 mg dL p lt 0 001 26 1 2 16 67 mg dL 1 2 p lt 0 001 52 26 36 93 mg dL 1 2 24 35 mg dL 52 29 26 mg dL 31 41 mg dL 52 26 26 26
123. 1 3596 1 229 26 HbAic 1 4096 0 959 1 8196 1 0496 HbA1c 52 30 HbAic 38 26 F 9 HbA1c 1 0 5 6 4 0 8 12 20 26 30 34 38 46 52 n 74 74 74 74 74 74 74 72 71 71 n 62 62 62 62 62 62 61 61 59 58 58 HbA 25 HbA 7 0 6 596 26 HbAi 7 09 26 HbAi 7 09
124. 1 2 2 2 1 30 1 2 30 30 30 52 2 lt 1 1206D 172mg dL 1 3 lt 1
125. 1 3 1 2 5000 ng plate CHO wtro 5000 ng mL zn vvo 2000 ng kg 1 vztro CHO 68 92 ng kg a 0 18 70 250 CD 1 QD 2 65
126. 1 2 26 C HOMA 26 1 76 1 2 1 37 1 2 p lt 0 001 6 1 2 26 p lt 0 001 26 1 2 p lt 0 001 2 2 1 2 p lt 0 001 6
127. 2 5 3 26 26 10 1 1 1 2 0mg 1 2 0mg 1 gt 1 1 3 26 26 3 2 0 26 52 SU r 2 26
128. 2 IF IF IF IF IF IF 2008 IF PDF IF 2008 IF 2008 21 4 IF 2008
129. GLP 1 1000 ob ob EDso 0 009 g db db GLP 1 3 GLP 1 oJ mv O 100 200 4 300 400 r 0 802 ee 500 O 9 oO T_TTTTTTITTTTTTTTITTTTTTTITTTTTTTTTTT TTTTTTTTTTTTITTT TITT T T T T T Zero 0 001 0 01 0 1 1 10 100 1000 0 200 400 600 800 1000 on 99D db db A db db n 66 0 001 0 01 0 1 1 10 ng n 12 16 27 13 13 0 1 1 10 100 1000 ng GLP 1 n 12 17 20 21 14 9 B 1 ng n 34
130. TEAE 20 396 15774 27 496 17 62 6 8 5 TEAE 8 19 6 5 28 GWBX WCK 3 0 mmolL 54 mg dL 3 0 mmolL 54 mg dL GWBW
131. L L L L L L L L L histidylglycyl L glutamylglycyl L threonyl L phenylalanyl L threonyl L seryl L aspartyl L leucyl L seryl L lysyl L glutaminyl L methionyl L glutamyl L glutamyl L glutamyl L alanyl L valyl L arginyl L leucyl L phenylalanyl L isoleucyl L glutamyl L tryptophanyl L leucyl L lysyl L asparaginylglycylglycyl L prolyl L seryl L serylglycyl L alanyl L prolyl L prolyl L prolyl L serinamide 6 LY2148568 7 CAS 141782 76 5 1 1 2 5 i 7 5 3 mg7mL lt 0 1
132. ZDF 1 S HbAi 15 oO 5 0 1 10 100 1000 10000 owW hg ZD 33 7 wvo 22 db db ob ob 0 001 10 ug GLP 1 0 1 1000 ug 1 db db EDso 0 003 ug EDso
133. W 1 2 V 1 2 gt gt 2
134. 1 2 SU SU BG SU TZD 1 SU BG TZD SU BG SU TZD BG TZD 4 1 60 2 C
135. 20 0 77 mg 0 74 mg 0 62 mg 5 3 1 2 4 5 1 5C 36 25 C 6096RH 6 5 2 8 5 1
136. 76 1 2 71 1 396 1 76 1 2 1 49 1 71 5 3 4776 1 2 11 396 8 71 SU 264 1 2 267 6 8 18 264 1 2 12 09 32 267 19 7 52 264 1 2 26 296 70 267 1 2 SU SU 52 gl 1
137. 3 4 tmax AUC 51 1 2 Cmax AUC tmax min 909 CIl 90 CI 0 MK 220006 UN nnUoe yns onovym eleoyoeoe al R 35 15 15 1 05 1 00 1 11 1 06 1 00 99 DS S 35 15 15 0 97 0 93 1 06 1 01 2 00 1 01 1 11 5 20mg 35 19 18 0 93 0 86 0 97 0 90 2 00 2 0 7 0 1 02 1 04 0 25mg 30 22 21 0 82 0 75 0 95 0 90 2 50 0 0 3 5 0 89 1 00 40mg 30 35 21 17 0 72 0 57 0 60 0 50 4 00 0 0 6 0 0 91 0 71 _ ii 1 60 24 21 0 85 0 78 0 94 0 88 0 00 8252 EL 99 el 30 24 23 0 55 0 50 0 96 0 90 3 00 0 60 0 UN 60 24721 1 01 0 92 1 00 0 92 0 08 1 OF JE 99 Eh 30 24 23 0 73 0 67 1 05 0 96 3 50 0 79 1 14 1 2 n
138. 1 2 24 SU 1 2 5 10 ng 1 2 5 10 ng C AUCo 2 12 419 6 6 1 2 30 1 GLP 1 glucagon like peptide 1 DPP 4 dipeptidyl peptidase 4 2
139. 5 BMT 18kg mz 35 kg m2 6 Visit 1 90 59 Visit 1 6 1 1 2 180 mm Hg 110 mm Hg 3 4 1 5 ALT GPT
140. INR 1 1 Hb 12 9 gdL 3 4 INR 68 HMG CoA AUC 40 Cmax 28 tmax 4
141. 2 2 0 mg 26 Week 8 Week 12 Week 20 Week 26 n 73 78 86 88 pg mL 203 63 254 52 248 74 236 79 4 81 2 0 8 mg 2 0 mg 1 15 LAR 104 2 0 mg 1 1 2 1 2 30 LAR 105 625 lt C s CrCL CrCL C CrCL Ca s 22 8
142. 22 ng kg PF 2 ng kg PF PE 94 ng kg PA 60 0 6 68 760 FO CD 1 BID gt 6 ng kg 25 6
143. 24 105 mg dL Pair Feed 3 83 0 61mg kg min Pair Feed 7 2 0 63 mg kg min 9 6 0 82 mg kg min n 9 n 9 Pair Feed n 8 mgke 12 5 1 5 p 0 0003 p lt 0 02 10 5 Vs 66 Pair Feed 1 0 P lt 0 035 vs 5 0 lt 0 5 o CT T TTY 1 YOo a _oo oO 2 5 Tp 0 y 0 4 60 30 0 30 60 90 120 150 180 0 45 150 180 45 150 180 45 1
144. 26 Zucker fatty fa fa 9 1 2 6 ng kg day 6 1 31 9 0 7 g 27 8 0 3 g Pair Feed 27 7 g 40 0 3 g Pair Feed 9 6000 35 _ 30 9 25 Pair Feed 400 300 Pair Feed n 10 11 D 0 001 vs One way ANOVA post hoc t test Zucker fatty fa fa 7 wzvo 1 21 ZDF 9 1 1 1
145. 38 1 39kg 8 8 Homeostasis Model Assessment of beta cell function HOMA 8 C HOMA 8 26 1 88 1 32 p lt 0 001 7 3 26 2 2 2 26 7
146. 4 50 kg 5 HbAi 6 59 10 09 6 Visit 1 qa HbAi lt 9 5 2 1 10 8 0 8 mg 2 0 mg 1 lt 3 10 10 3 0 8 mg 2 0 mg 1 10 10 2 0mg 10 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 1 1 gt HbAi 10 HbA
147. 5 396 18 10 0 34 1 2 0 69 6 2 3 59 6 12 1 2 6 89 6 23 1 2 1 1 2 9 8 33 338 5 696 19 340 p 0 044 1 2 9 296 31 838 4 196 14 340 p 0 009 2 496 8 840 1 2 1 596 5 838 1 2 23 19 6 78 338 16 596 56 340 p 0 034 SU
148. 83 5 84 4 No 84 15a SE 114 86 16 89 uuu 90 kN 90 4 gt 91 96 1 96 2 tk 96 3 96 4 EE 96 5 NES 103 6 103 sa 103 8 103 9 103 10 103 11 103 12 8KS 103 13 0 103 14te NRNANAANNNAS 103 15 104 MRA IE 104 17 104 KERS CN NN OR 105 1 SL et 105 2 107 XI 108 1 108 2 109 1 1 2 mg
149. Buffer 11 10 9 8 7 6 Laog mal L GLP 1 cAMPE cAMP 1009 6 9 n 3 GLP 1 cAMP GLP 1 GLP 1 32 2 2 1 1 2 0 8 2 0mg 1 10 10 HpAi 0 4 0 3 0 8 mg 1 0 0 796 2 0 mg 1 5 0 79 20 5 20 4mg dL 0 8 mg 25 2 10 9 mg dL 2 0 mg 50 8 27 8 mg dL 2 8 8 26 9 mg dL
150. 678 BCB112 I QT PKVPD TAR 103 II 2 2 5 5 0 7 5 10 0 mg 9 LAR 104 I 2 O 15 0 8 2 0 mg 9 BCB106 nl 2 26 10 14 BCB107 I 7 vitrofn vivo 3 1 ALkza I 3 1 001 LAR 101 I 2
151. p lt 0 001 LDL p lt 0 001 HDL 21 lt 1 5 1 5 AG 1 5 AG 26 1 5 AG 5 59 ng mL 2 97ug mL 2 62 ng mL p lt 0 001 16 26 218 145 118 55 496 27 12 79 213 68 81 99
152. 0 5ng mL 24 C 20ng 54 C 1 2 8 0 2 60 19 2 AI 368mg dL 387mg dL
153. 2 9 6 7 22 7 65 0 18 70 250 250 ng kg C CD SD QD 2 GLP 1 C 65 1 2 5 6 30 8 C C 65 mg kg QW QW 70 70 2 1 2 PLG 0 3 1 0 3 0 PLG 0 3 10 3 0 C 21 14 33 27 33 19 17 44 41 57 13 13 29 46 47 7 13 31 27 30 9 0 1 3 7 4 0 1 1 1 6 amp 2 1 3 6 4 16 6 0 9 5 3 15 7 C QW 1 0 3 0 mg kg C 6
154. 20000500C0o0CCoo0000 1 PP P 8C
155. EU BYDUREON BYDUREON Amylin OE i 2012 2011 1 2 msg 2 2 SU TZD Met SU Met TZD 1 2 mg 1 2 mg
156. 1 2 GWAB CL F CL F 2 CrCL gt 50 mL min 189 869 8496 amp UR ENC IOLLT EW Cata ES 0 owas ik HE 5 amp QWAB TIFK oe 3 I S 15 10 Le 5 4 1 gt TS EE O GWAB 222 WAB
157. 10 10 10 YNS NeeeoAtiebfeeohS 10 12 10 13 10 IL 10 V 11 1 LE 11 2 OO 11 NN 12 VI 31 1 31 2 EE 31 kkk 42 1 42 2 53 SR 53 GC TSE NR 54 BR 55 HP 55 7 E 56 57 1 Ek 57 2 Lu 57 3 KR 57 4 0 USI2SeM 57 5 enc 58 6 59 7 66 8 70 9 6k 82 10 uuu 82 11 ll 83
158. 24 10 9 mg dL 44 6 mmolL KK 5 5 mmolL 0 4 mg dL HbAr 5 5 2 5 0 mg dL 3 2 6 mg dL 7 1 5 mg dL 72 3 GWCK 1 GWBX 26 2 0mg 1 26 1 ICSD BSB108 1 1 2
159. 2 208 211 2001 030 308065 DMA1 0003 11 12 2012 2013 030 308044 DMB2 0005 GLP 1 DPP 4 http wwwjds orjp jds_orjp0 uploads photos 797 pdf 56 57 58 59 60 9 2 176 179 1990 030 308052 DM90 0002 68 81 1994 030 308047 DM94 0002 1 6 11 1996 030 308092 DM94 0003 2 778 779 1998 030 308093 DM98 0008 8 1 14 22 2001 030 308091 DMA1 0016 61 62 63 64 65 66 67 68 Weber G et al SOUTH AFRICAN MEDICAL JOURNAL 474 475 1967 030 308071 DM67 0001 DIABETES NUTRITION AND METABOLISM 2 1 75 93 1989 030 308097 DM89 0001 49 659 664 1991 030 308049 DM91 0001 53 7 505 508 2010 030 307687 DMB0 0002 Lopez Ruiz A et al Pharm World Sci 32 5 559 561 2010 030 307903 DMB0 0001
160. 41 1 1 gt 1 2 50 350 pg mL 2 3 ITEMA 625 625 PK PK PD 8 1 1 29
161. 6 5 14 12 20 1 CWCK 7 1 24 1 2 9 8 33 2 10 9 Ee 1 n 215 B n 212 8 1 6 3 2 B 3 0 4 2 0to4 gt 4 to 8 gt 8 to 12 gt 12 to 16 gt 16 to 20 gt 20 to 24 gt 24 A 215 A 213 A 207 A 205 A 203 A 199 A 195 B 212 B 212 B 210 B 208 B 205 B 205 B 203 1
162. 1 1 2mg BYDUREON 2mg 3 BY DUR EON 3 BY Byetta DUR Duration EON Long acting 2 1 JAN Exenatide JAN Exenatide INN 3 tide 3 H His Gly Glun GIY Thr Phe Thr Ser Asp Leu Ser Lys GIn Met Glu Glu Glu Ala S 1 10 15 Val Arg Leu Phe Ile Glu Trp Leu Lys Asn Gly GIY Pro Ser Ser Gly Ala Pro Pro 20 25 30 35 Pro Ser NH gt 39 4 CisaHzszNsoOsoS 4186 57 5 L L L L L L L L L L L L L L L L L L L
163. 100 300 1 000 3 000 gt 3 000 ng kg 1 1 5 000 gt 5 000 ngykg ng kg CD 1 0 6 68 760 760 gt 60ng kg 1 1 21 21 BID 91 CD 1 0 18 70 250 250 gt 18ng kg 1 10 20 QD 91 30 10 20 CD 1 0 18 116 760 760 gt 10ng kg 25 25 BID 182 1 SD 0 10 100 1 000 1 000 gt 18ne7kg 1 10 10 QD 28 SD 0 18 70 250 250 30 10 20
164. 20 6 1 3 25 430 F1 gt 68 nsg kg 6 F1 gt 68 ng kg F1 760 ng kg 1 F1 760 F0O F1 QW 1 BID 1 2 1 NZW New Zealand White PF Pair Feed 95 X 1 2mg 2 3 8
165. 7 PLG 2 2 0 mg 1 10 8 8 2 0 8 mg 2 0 mg 1 10 1 3 2 0mg n 9 0 8mg n 10 n 10 mg 30 G S H3 0 1 2 3 4 5 8 7 8 9 1 12 13 14 15 16 17 18 19 20 0 8 mg 2 0 mg 1 10
166. 1 39 GLP 1 53 GLP 1 GLP 1 cAMP 19 2 N 2 GLP 1 4 DPP 4 7 50 50 PLG 1 1 1 2
167. 1 0 1 0 12 4 1 5 0 61 46 16 62 7 58 4 6 10 1 22 1 0 1 0 12 3 0 3 0 37 1 0 1 0 12 4 0 4 0 49 2 0 2 0 24 2 0 2 0 24 1 4 5 0 61 80 818 556 818 556 ES MeHDA ver140 adptAver140 1 0 1 0 12 1 2 3 0 37 0 1 1 0 12 1 0 1 0 12 2 1 3 0 37 5 0 5 0 61 1 1 2 0 24 1 0 1 0 12 0 1 1 0 12 4 0 4 0 49 3 0 3 0 37 1 0 1 0 12 4 3 7 0 86 2 0 2 0 24 0 1 1 0 12 3 1 4 0 49 0 2 2 0 24 2 2 4 0 49 0 1 1 0 12 1 0 1 0 12 0 1
168. 336 161 47 99 1 2 333 107 333 10 3 09 333 97 29 196 336 130 38 79 1 2 333 226 67 99 26 HbA p lt 0 001 16 gt 26 7 TEAE Treatment emergent adverse event 42 6 145 340 1 2 45 69 154 338 TEAE 9 19 31 1 2 23 79 80 7 19 6 24 1 2 9 896 33 6 296 21 1 2
169. 5 20 GLP 1 e O GLP 1 20 1009 EDso 0 18 ng GLP 1 6 26 ng GLP 1 2 yo GLP 1 0 1 GLP 1 n 16 n 3 6 GLP 1 n 4 10 36 3 7 yo
170. Dn 121 166mgdL 0 C1P 3W J S L 3 036 10 14 18 22 26 303336 40 44 48 52 LAR 105 63 10 SU SU SU SU 4 DPF 4 1 GLP 1 I SU Recommendation 55 7 8 2 1 1
171. MRI 3 2 73 2008 R 1 BE 3 mEq CT CT Grade 2 PaO2 60 mmHg room air 1 3 Re Cr 2 0 mg dL 5 10 mm 7 CRP 15 mg dL gt Rg 3 2 3 80 mmHg Ss 0
172. 1 2 8 C 2 4 30 85 15 1 0 3 1 0 3 0 mg kg 2 1 C C 2 mg 1 1 1 16 2 2 2 3
173. 74 396 Ca s C 45 pgrmL 1 600 1 400 1 200 1 000 8S H 8 a 600 200 0 n 84 n 56 n 10 CrCL 80 mL min CrCL 50 mL min 80 mL min CrCL 30 mL min 50 mlmin CrCL Cockcroff Gault 2 0 mg 2 0 mg pg mL MM 7 84 116 6 252 7 300 3 369 6 1074 7 56 225 3 282 6 368 7 436 6 1562 9 10 162 1 398 2 523 4 714 4 1076 8 CrCL gt 80mL min 50mL min lt CrCL 80mL mm
174. 1 10 0 6 155 225 204 185 mg dL 289 mg dL 225 130 mg dL 148 mg dL 85 IU L 55 U L gt 2008 1 2 3 CT
175. 2 1 LAR 102 I 2 1 LAR 105 2 1 1 2 1 BCB106 ll 2 1 12 BCB108 2 O 1 1 2 13 GWBR ll 2 1 14 GWDC 2 1 TZD 15 TZD Met 52 Met TZD
176. 2 0 mg HbA 4 5 1 2 33 2 2 0 mg 1 1 2 10ng 1 2 30 14 1 2 1000 mg Cmax 16 596 1 2 21 6
177. 0 8 mg 50 0 41 1mg dL 2 0 mg 59 7 26 8 mg dL 2 0mg n 9 0 8mg n 10 n 10 i ay SU YIM 29 2 1 10 2 mg 1 vo 1 21 ZDF 9 1 10 100 1000 3000 9000 g 28 p lt 0 0001 10 20 28 HbA nm 14 HbA n 7 mmoD HbAi 25 p lt 0 0001 8
178. 108 2 1 FDA FDA 1 22 ng kg 2mg 1 1 49 5 68 ng kg 2mg 1 1 5 4 0 3mg kg
179. 12 796 62 7 69 55 6 79 49 6 09 6 43 5 89 GWBX WCK 2 mg 1 818 556 426 52 19 8 4 161 19 796 104 12 796 62 7 696 55 6 796 49 6 096 43 5 89 2 1
180. 2 70 1 GWBX 215 21 9 8 GWCK 340 63 18 5 SU SU 26
181. 2 0mg 1 tt 5u9g 10g 1 2 _ 1 2 Ji 2 26 26 2 1 0 4 26 52 C 1 26 1 1 2 1 2 SU 2 0 mg 1 1 2 1 2 10 ng 1 2 26 26 26
182. 20nmol L 20nmol L 15 15 4 2 2 QO O o CC 0 3mmoL 27 5mmoWL 3mmoML 3mmoL 27 5mmoML 3mmolL 50 60 70 80 90 100 50 60 70 80 90 100 n 5 19 GLP 1 1 n 5 19 35 7 yo 24 ZDF 14 60 0 21 ng 2 1 ng mL hr 90 34 mmolL
183. 400 mL 2 SIRS 1 gt 38 C 36 C 2 2 2 gt 90 3 gt 20 PaCO2 32 torr 4 gt 12 000 mms 4 000 mms 1 2 Grade 1 10 2 Grade 2 3 Grade 3 48 1 2 3 CT Grade2 2010 2009 Hz RRCP ES
184. Cmax tmax 1 2 gt 34 22 40 mg 1 2 10ng tax 4 AUC Cmax 409 2896 ng mL mm e s 3 0 Fr 9 4 12 16 20 Mo 40 mg 1 1 2 10 ng 4
185. GWBX 26 030 308006 GWBX 52 030 308008 JiL et al J Diabetes Investig 4 1 53 61 2013 030 308103 DMB3 0001 Onishi Y et al J Diabetes Investig 4 2 182 189 2013 030 308168 DMB3 0006 GWCK 26 030 308007 GWCK 52 030 308009 Fineman M et al Clin Pharmacokinet 50 1 65 74 2011 030 307696 DMB1 0001 030 308005 Drucker D J Lancet 372 9645 1240 1250 2008 030 307718 DMA8 0002 Bergenstal R M Lancet 376 9739 431 439 2010 030 307691 DMB0 0004 Blevins T J Clin Endocrinol Metab 96 5 1301 1310 2011 030 307710 DMB1 0003 Diamant M Lancet 375 9733 2234 2243 2010 030 307692 DMB0 0003 Norwood P Clin Ther 34 10 2082 2090 2012 030 307961 DMB2 0006 HbA1c 030 308019 Linnebjerg H et al Br J Clin Pharmacol64 3 317 327 2007 030 307694 DMA7 0002 Linnebjerg H et al Int J Clin Pharmacol Ther 49 2 99 108 2011 030 307716 DMB1 0002 Drucker D J Diabetes Care 26 10 2929 2940 2003 030 307699 DMA3 0002 Goke R et al J Biol Chem 268 26 19650 19655 1993 030 307711 DM
186. 2 8 C 4 1 W 14 2 96 IT 0220 JJAl 2 gf 2mg 2mg si cd 1
187. 2mg 1 1 1 7 3 1 3mg kg 2mg 1 1 10 9 FDA Pregnancy Category C 2012 1 An Australian categorisation of risk C 2012 11 of drug use in pregnancy FDA Pregnancy Category C Animal reproduction studnes have shown an adverse effect on the fetus and there are no adeguate and well controlled studies in humans but potential benefits may warrant use of the drug in pregnant women despite potential risks An Australian categorisation of risk of drug use in pregnancy C Drugs which owing to their pharmacological effects have caused or may be suspected of causing harmful effects on the human fetus or neonate without causing malformations These effects may be reversible Accompanying texts should be consulted for further details 109
188. 3 7 2 3 6 2 13 3 16 89 1 3 VI nmolL ng kg Irwin ICR 10 02 80 300 1500 ng kg 300 ng kg 2 1500 g kg 4 CR 8 02 30 300 1500 ng kg ia Rota rod CR 10 CR 10 CR 10 05 30 300 1500 ng kg 0 30 300 1500 0a 30 300 1500
189. 30mL min lt CrCL 50mL min CrCL Cockcroff Gault 1 2 17 gt CrCL gt 80 mL min 8 CrCL 50 80 mL min 8 CrCL 30 50 mL min 6 CrCL lt 30 mL min 8 1 2 5 10 ng tu 1 45 2 12 3 16 5 95 ti pg mL A pg mL 0 8 12 16 20 24 0 4 8 12 16 20 24 TD 1 2 46
190. 45 13 496 161 47 99 336 130 38 79 26 HbA 26 GWBX GWCK 118 27 161 45 b 16 34 8 7 19 9 23 5 28 8 29 6 5 4 11 8 20 0 6 i 0 0 0 4 10 6 0 0 0 0 0 0 3 1 6 2 13 3 6 7 1 3 10 6 8 ae 5 9
191. 50 ICso 0 59 0 10 nmolL GLP 1 1Cso 0 14 0 02 nmolL 96 100 gt 80 1 e eo S S GLP 1 kr 1 40 1 ee 20 a o 1 lt Buffer 11 10 9 8 7 6 5 Log mol L GLP 1 Buffer 25IIGLP 1 1009 9 cAME GLP 1 pH7 4 37C 20 cAMP GLP 1 cAMP cAMP 509 ECso 0 31 0 05 nmolL GLP 1 ECso 0 23 0 06 nmol L 96 120 2 100 1 3 80 2 60 M 4o 5 GLP 1 20 _o
192. 2 0 mg 1 10 2 26 HbA HbAi 7 0 6 5 8 6 24 gt HbAi 26 26 HbAi 1 439 0 079 1 2
193. QW C C GLP 1 C QW 1 QD 1 1 PLG Z7 50 50 p lt 0 005 p lt 0 0001 amp p 0 0248 93 5 ng kg Ss a 0 6 68 760 760 CD 1 BID 25 28 25 15 7 3 4
194. 2 8 kg HbAi 1 8996 25 1 8196 125 1 139 2 0 mg HbA C HbA Ca 48 gt 0Titer 25 Titer RNN 125 Titer HbA1c 1 500 2 000 pgimL Caxss HbAi 125 25 0 HbAi C 25 75 83 5 pg mL RECso
195. 4 1 1 1 2 GWAB
196. C pmolL p lt 0 02 p lt 0 009 QD BID n 3 n 3 P vs One way ANOVA Post hoc t test yo 1 21 ZDF 9 1 1 10 100 ng 28 C C p lt 0 03 ZDF QW 1 10 100ug 28 VGTT 180 270 QW C 3 180 270min pmol L 400 200 n 6 5 6 5 0 0 1 10 100 1 000 10 000 ug 8
197. Lewis 50 3 mmol L 7 5 mmolL 3 mmolL 6 4 1 5 7 5 mmol L 3 mmolL 13 5 2 8 P lt 0 01 GLP 1 12 7 3 9 P lt 0 05 n 19 GLP 1 n 5 n 19 n 6 pg isleVmin pg islet min GLP 1
198. Yamaguchi K et al J Control Release 24 81 93 1993 030 308076 DM93 0005 Calara F et al Clin Ther 27 2 210 215 2005 030 307723 DMA5 0002 030 308004 106 107 XI 1 2011 6 EU 2012 1 2 2mg 1 2013 1 1 2 mg
199. 00 0180 189 550 1 1 88 6 5 1 BDOO2A B504 BD 12 12 0001 14 11 IT 00220 JJAI 2013 4 102 10 11 12 19 14 2mg 1 1 0 75mL 1 1 1 2005 4 28 2012 3 30 2mg 22400AMX00664 2013 2 22
200. 1 36 mg dL 2 1 68 mg qL 88 mg dL 10 12 9 13 1 3
201. 1 2 1 1296 0 079 HbAi 1 2 0 31 0 099 6 95 0 49 0 14 HbAi 95 0 4 1 2 1 2 p lt 0 001 6 n 307 n 263 8 71 0 06 8 67 0 06 0 2 0 4 0 6 0 8 1 12 GO p 0 001 1 8 p lt 0 001 vs HbAi 52 gl 52 HbAic 1 8296 1 049 1 2
202. 1 0 12 0 2 2 0 24 3 0 3 0 37 0 1 1 0 12 2 0 2 0 24 5 0 5 0 61 21 1 22 2 69 1 0 1 0 12 1 0 1 0 12 3 0 3 0 37 1 0 1 0 12 11 0 11 1 34 0 1 1 0 12 0 1 1 0 12 2 0 2 0 24 2 0 2 0 24 1 0 1 0 12 1 0 1 0 12 1 0 1 0 12 1 0 1 0 12 3 0 3 0 37 12 0 12 1 47 1 0 1 0 12 0 2 2 0 24 2 0 2 0 24 2 0 2 0 24 43 12 55 6 72 1 0 1 0 12 1 0 1 0 12 mm 2 1 1 2 0 24 Se 151 8 159 19 44 23 1 24 2 98 1 0 1 0 12 81 5
203. 119 201 TEAE 59 6 296 12 59 20 49 41 19 496 39 9 59 19 9 0 18 8 096 16 6 096 12 5 09 10 1 GWCK 5 6 7 gl SU BG TZD 2 SU BG SU TZD BG TZD 2 2 0 mg 1 1 2 10ng 1 2 26 HbAi 26
204. 12 3 16 5 95 ti CL E CL F 0 9 L h 3 4 L h 1 2 gt GWCC 18 75 2 3 2 15 75 85 CrCL 30 80 mL min 15 45 65 CrCL gt 50 mL min Cockcroft Gault CCL 30 80 mL min 11 4 5 10
205. 8 3 1 2 8C 2 4 30C 1 1 2 2 1 2 3 3
206. 9 76 bpm 64 GWCK 3 35 10 02 bpm 17 1 2 8 65 7 1 2
207. Intent To Treat gt 20 24 79 4 GWBX GWCK 818 556 818 556 ES Ed MedDRA ver 14 0 GDRA ver140 1 0 1 0 12 0 1 1 0 12 0 1 1 0 12 1 0 1 0 12 0 1 1 0 12 0 1 0 12 0 1 1 0 12 1 0 1 0 12 1 0 1 0 12 1 0 1 0 12 1 0 0 12 0 2 2 0 24 1 0 1 0 12 0O 1 1 012
208. QW 1 1 mg kg 4 4 0 0 11 0 44 1 1 mg kg QW 3 QW 1 1 mg kg 6 6 0 0 11 0 42 1 1 mg kg QW 9 QW 1 QD 1 1 BID 1 2 KLH Keyhole limpet hemocyanin 1 91
209. ng 971 822 pg 7mL 6 18 6 760ng kg 1 2 0 8 2 5 6 24 2 260ng kg 1 2 0 0 8 ex vo 43 300 pg mL 3 000 pg mL 0 8 1 79 0 5 5 496 gt 380 ng kg 1 2 760 ng kg
210. 0 100 1000 3000 9000 ng 10 20 28 10 ng 100 ng 1000 ng g day 40 Sm 20 1 10 11 20 21 28 rr 0 1 10 ZDF 100 4 le_ oOo so 10 20 28 10 000 oo 6 1 10 1oo 1 9oo 1oooocuo n 7 37 4 7 wzvo 26 Zucker fatty fa fa 9 1 2 6 ng kg day 6
211. 20 lux hr Bi Ne 200W hr m2 2 30 4 30 C 4 3 75 RH Re 120 ux hr ee 200W hr mz 6 7 8 9 10 11 12 13 14 2 1
212. 22 99 155 78 1 2 77 26 HbAi HbAi 1 43 0 079 1 2 1 12 0 079 HbAi 1 2 0 3196 0 099 959 0 4996 0 1496 HbAi 959 0 49 1 2 26 52 136 74 1 2 62 OM n 307 n 263 2 8 71 0 06 8 67 0 06 0 4 J 0 6 oa 1 0 1 12 1 2 1 4 1 6 p 0 001
213. 50 180 n 8 9 IS 1 mgkg ng mL p lt 0 01 vs Pair Feed One way ANOVA post hoc t test D 0 001 vs One way ANOVA post hoc t test Zucker fatty fa fa 180 7 yo 1 21 ZDF 9 1 1 10 100 1000 3000 9000 ng 28 p lt 0 0001 ANOVA EDso 403 ug 0 23 1og units 2 1
214. 93 0001 in vivo 030 308018 Young A A et al Diabetes 48 5 1026 1034 1999 030 307698 DM99 0001 Parkes D G et al Metabolism 50 5 583 589 2001 030 307731 DMA1 0001 030 308016 030 308017 Gedulin B R et al Endocrinology 146 4 2069 2076 2005 030 307707XDMA5 0004 030 308001 Gedulin B et al Diabetologia 44 Suppl 1 A197 Abstract 758 2001 030 308096 DMA1 0002 LAR 103 030 308027 26 GWBX 030 308020 030 308028 030 308039 030 308043 Kothare P A et al Int J Clin Pharmacol Ther 45 2 114 120 2007 030 307709 DMA7 0001 Soon D et al J Clin Pharmacol 46 10 1179 1187 2006 030 307713 DMA6 0002 105 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55
215. 94 3 430 0 6 68 460 760 CD 1 BID 68 ng kg 25 6 15 6 760 pg kg 3 430 QW 0 3mg kg SD 0 0 3 1 0 3 0 mg kg 25 3 1 6 15 0 3 mg kg 1 7 4 7 10 9 0 8mg kg 3 0mg kg
216. QD 91 10 20 SD QW 9 mg kg gt 3 mg kg 15 15 0 1 3 9 mg kg 2 1 18 3 0 10 100 1 000 100 gt 13 4 ng kg 8 8 QD 28 KLH 278 0 1 2 13 4 150 150 4 4 BID 91 gt 100 ng kg 0 2 2 18 150 150 gt 150 ng kg 6 6 BID 2783 1 1000 pg kg
217. g 2 0mg n 8 6 1 Cmax pg mL 64 3 90 4 137 85 6 tmax h 2 00 0 980 8 00 2 00 0 500 8 00 n 8 5 Cmax ss pg mL 141 20 6 582 61 1 9 10 Cay s pg mL 81 2 26 2 345 31 7 tss max h 2 08 1 88 72 0 95 9 1 92 216 AUCweek 9 to io pg h mL 13900 25 6 60800 29 0 26 gt 30 2 2 0 mg 1 8 Cakes Cavss AUCweek 9 io 9 10 AUC 2 mg 1 26 203 pg mL 12 254 pg mL 20 248 pg mL 26 236 pg mL 8 50 350 pg mL
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