不 彗昴 締 部 生 一 次 衛 第 口印 食 品 事 幹 薬 薬 医 議
Contents
1. BIS Ee MENA2. RFRA 1 JAN Insulin Glargine Genetical Recombination Insulin Glargine Biosimilar 1 C261Ha0sN72078S6 6062 89 WER Am RR Gty Te Val Ghu Gin Cys C ys Thr Ser Ile Cys Ser Leo Tyr Gin Leu Ghu Asn Tyr Cy5 Gly 1 3 10 15 31 B Bl Phe Val Asn Gln His Leu Cys Gly Ser His Leu Val Gh Ala Leu Tyr Lev Val Cys Ghy 1 5 10 2 Ghr Arg Gly Phe Phe Ty Thr Pro Lys Thr Arg Arg 3 2
3. 24 3 CYP2D6 CYP1A2 CYP2C19 1 2
4. VIP VEY YOR IM Oth BB 4 CYP2C8
5. 1 5 2 3 24 000 5
6. fa gt BET FA EE BE A OD A
7. 8 OREA E amp
8. N 2003 2010 NAGS 2011
9. I COMPARE FM ACTH DEE 18 BLASS HT COMER A A Ue SE Paz
10. 49 50 E 4 2
11. 1 30 60mg 120mg 1 3 1 30mg 60mg 90mg 1 3
12. VEG VEGF
13. NPH 3 BVH 1 SLA 1 0 25 0 5 1mg AUC mg ng h mL 0 25 n 6 7 5 0 9 0 5 n 6 15 3 4 4 1m 6 31 5 12 0 Cmax Tmax t 2 ng mL min 6 8 1 8 62 5 87 2 30 46 44 12 6 13 6 27 7 Fe EZ PRE ng mL Img n 6 365 7 05mg n 6 30 4 0 25mg n 6 h Cmax OLE FRU Tmax OIE RBH 072
14. INABA YD _ 8 ei 1 47 a 1 3 b 30ug 150g AUCo ss d AUC0 2ah e AUCo sh 1 AUCO sh SEE 0 25mg 1 1 9 30 R S OR TO 3 9 a y 3D 300mg 2mg f 2 5 5 0 95 0 90
15. 39 40 Fa ot EF LH PR REC ES REED FEE MH 1 4 1 6 1 2 B 2014 5 30 2014 10 er
16. cw CYP3A4 ROR RIBAS 2
17. NMO 186 SED BRIEF ae NMO PEM NMO Ik EEL CRARRUBMERET SZEEOR 30 40 1 55 3 809 NMO 4 NMO IgG ee 5 2 3
18. 1 1 3 3 20 e 2003 24 FASE
19. 2 2 e GI BG TZD 2014 6 100 DIE gt
20. HTL1 2 4 2 29 2 6 74 60 2014 7 HT 1 1 2 4
21. ME 0 1 5 ARE Se BE FES Kr FEB AST GOT ALT GPT ALP y GTP ER BUN ma AR ZU EPA A ELA SHIA BE SDT EE BER Bei SIR MIT SEHE ED 8 u abe
22. 1 5 2 3 15 700 38 000 5 T
23. Tr IE TR En HA 4 PARMA SNA MAS k MBAS 3 232 ne 2 O e mern RTE Ah
24. 104 1 1997 EI RUE FREE ARTEN TS ae ADT DI Te
25. 1 4 80 o te Laid KBR 23 24 LY2963016 1 8 BS 20xx xx 1 pom 8 BS o BS ames Insulin Glargine BS Inj Lilly 1 THR Rr Rs HEE 2 8 C
26. 24 5 2 4 25 26 LY2963016 BS AIRES ELLE OR RE CAS E MBE ERA MAL O A BR MA ARA ROT ek NYR IRTE 6 HE ROBER IRE ELL CARE 7
27. Es P430 P450 11 303 403 3 6 0 8 87 1 4 136
28. BER 10mg 0mg D 10mg ZNC219 10 i 1 872123 1975210 A 201X4EX Al 14100AZZ04028 MSM LEN SHE MMO PM MEL ENT AAI TREE FAO PA E LEME EHE FEIERTEN Bit DAI BRENNER EDR FED DEREN SEHE BSR
29. 1 o 2 3 9 1 gt 18 a b c d
30. 24 0 5 kg 2 CAPS FRE 3 El RENA E 1 C AUC Con 90 80 125 m 27 28 LY2963016 BS 200 1 34m EA 100 8 SS Ee C pmol L es 0 6 12 18 24 hp 0 5 ks
31. FR RCH SRE OK MTEC T CoM 2 1 2 3 4 5 6 X
32. gt PMDA B AZ 1 lmeze mesweage 160
33. 7 8 3 1 1 1 1 9
34. 2 ERA 2 0 1 5 TORE RE wen sd mm ALT GPT a mens aS TER RE UN PER wee eH 5
35. 1 1 4 lt 20 1 4 80 gt 1 1 mL 2 3 1
36. 27 Niemi M et al Clin Pharmacol Ther 70 58 2001 28 Niemi M et al Br J Clin Pharmacol 57 441 2004 6 40 GE 45 Goto Kakizaki 46 Gromada J et al Diabetologia 38 1025 1995 47 Fuhlendorff J et al Diabetes 47 345 1998 48 Hansen AM et al Diabetes 51 2789 2002 541 0045 2 6 8 TEL 0120 034 389 2 6 8 Oo A S novonordisk DSP _DPP4 _20141007 O A S
37. 1 0 5 2 m 1 4 mg kg 556 8
38. REE ES A 2 REACT BEA o 8 8 8 e
39. Ait OQARE ORS ITHILT RYO TRAE AS ROO 6 Ek SB 2
40. 10 1 2 6 Ed EH 3 4 5 6 7 8 11 1 2
41. E MM BETA TE ie 2 RL OS RO PAMELA rege ZH a eel ea At Mo 5 wei ora B
42. 5 u 20 us A CHS 5 10g 5 14g 1 290 360pg mL 7 Ek 0 1
43. 74 a gt ao rg 836 268 32 1 ERIE RAIS gt MATER 126 15 1 34 4 1 28 3 3 27 3 2 1 08m 15 1 c 52 0 4 3
44. N N PTP PTP BARR Bok 0 25mg PTP 10088 108 x 10 0 5mg MER 5 2 3 Y 5 6 na 9 Hoelscher D et al 10 Eur J Clin Pharmacol 62 217 2006 11 Kajosaari Ll et al i2 2108 218 X 10 500 10 x 50 PTP 1008 108 x 10 210 21 X 10 500 10 x50
45. AUCo t 1 1 1 0 9 9 Cmg 1 0 1 0 9 9 2 AUC0 t 1 7 1 2 4 9 Cmax 1 2 1 9 5 1 mg 6 lt 0 8mL min kg Child Pugh B 9 C3 4mg Cmax AUC 12 2 5 4 3 9 2 2mg 1 3 5 40 80mL min 1261 Cis BRE 12 Cmax AUCo 20 39mr
46. Bs FR 1 3 0 25 0 5mg 1 0 25mg 1 1 1mg 0 30
47. 1 2012 11 AREA CHEM 102 2mg Smg 10mg SERIE 1 1mgkg 2 1 A 2mgkg 25 12 25 8 I HT1
48. 2 1 2 r 3 J El 30 ES ENE 1 2mg 8 EIS 10g kg 10mg SERBIEN BOB ER PERU RA BAOR ANE
49. 1 30mg 60mg 90mg MEL 1 3 1 0 5 2mgkg 1 3 4 1 4mgkg BD 90mg 4 1 20 30mg 60mg E CHUL 2 3 5 IB 0 57 2mg ke 1 3 4 1 4mg kg
50. g 42 RY ERAT AUC 24 WW OLA 1
51. 12 26 10 29 ee lt 29 8mg 22 3 BS EAS bh E BS mee 1 E BS 1 1 300 1 2 3 BS 1 1 300 1 1 4 20
52. 1 2mg PTP PTP PTpP 1 8 2 8 20mg 5 3 1 5 42 9ng mL 3 9
53. No 5 teduglutide No 6 Noe7 No 8 DEE No 9 No 10 1 BS BS No 11 2 0 25 mg 0 5 mg No 12 3 10mg 20mg No 13 4 52 mg NO 14 5
54. carglumic acid N N NAGS 1 5 2 3 100 5 _
55. 1 CL 2 PTP PTP PTP
56. PMDA 10 mg 20 mg AS AZ A ZA goog ENE PAE MENTE SEEM OB AED 1 30 60 mg 120 mg E CREU 1A 3 2 1 30 mg 60 mg 90 mg CAL
57. 209 FREE VEGF O 1 5 2 3 340 5 MP
58. OA 1 8 E 02 Kae a RR as 00 ke 02 2 4 Ba ote eee i Br ssp I 3 06 eN eee Base EBA 6 12 24 36 52 24 52 a LOCF lt HbAlc pH pH4 24 In vitro IGF 1
59. 5 E 1 1 1 RES ORS 2 2 1 2 3 4 MERKE FARZREREN 5 6 7 8 3
60. A8 REBT SEMI UR g REPRE EHRT A O PURE AS See FROBM WR FT
61. T 2 L gt a rn u 1 u 1 1 2 3 13 2 1 2 IUD
62. 8mg No 15 4 5 26 10 29 5mg Fl 10mg 2mg 5mg 10mg 40 mg mL 40 mg mL en lar A BS pair 74 0 25 mg 0 5 mg 10mg 20mg Q 3 a 52 mg 1 SG TERIA BEF MEO AER 2 BU dee D ED ea OM Smg 10 OS HER Smg 10mg
63. 4 3 7 2 g
64. PEA FAIR COA YAY VST BRET E GK HES ARRANCA 1 ADE B
65. a i 1 1 1 1 2 1 2 2 4
66. 9 2 15 18 1 089 1 20 1181181589 2 3 2mg 1 219 1 19 1 1 5 5 are 10mg 2mg 2 1 3 5 5 1 00 0 89 a 1 3 b 1 10mg 2 9 14 18 10 14 18 c 15 17 3 9 30 pg 150 g e AUC0 24h AUCH o 8 AUC0 6h 1 1mg LOCEF Last observation carried forward 1 1 0 25mg 0 5mg 1mg 1 3 12 HbA1c NGSP 92 HbAlc NGSP
67. GF BRA IE BR WE DEV MA MER LY2963016 BS E TE RE MEER FAUNA FREE ER UES SE B ag
68. 1 0 125mg EXIME OR DEERE IRA tN EAE F 3 Wastes 50 5 6
69. PN I V PN I V ARIE 2 PN I V 2012 EU 16 TI fp gt 3 7 FA EE 38 on 2 HS
70. 2 3 cm 3 4 lt A b gt a 2 8 C b c 30 C d 28 gt a 2 82C b 30 C c 28 10 1 Y 2
71. 1 2 3 4 5 PIDO 3 BRA PID PID PID
72. 3 4 Em 5 2 12 I BERRA RE HA Ek 2 3 13 1 7
73. 26 2 27 24 9 28 32 9 27 x FE ee hu II 2012 9 VREGFE PRIA SPLINES DME 1 VEGF DME AA VEG
74. Zollinger Ellison MALT it o rr 1 10mg 1 1 25 11 28 4
75. IUD 1 1 14 5 3 482 428 88 8 379 78 6 61 Pl 12 7 Mm 57 11 8 48 10 0 38 7 9 1 1
76. in vitro 3 4 2 Propranolol Hydrochloride JAN 2AS 1 1 Methylethyl amino 3 naphthalen 1 yloxy propan 2 o monohydrochloride H OH oR cH Y 3 HC E a 295 80 163 166C ER 100 99 5 1 40 10mg PTP 100 10 tx10 500 10 x50 1000 10 x100 500 1 Ohashi K et al A
77. 1 1 482 2 1 2 848 4 2 245 5 ERE CORBI 0 719 2 MPA 128 8mL 17 8mL 84 8 67 79 22 2 18 81 met a 82 393 6 1242 2 MPA 83 271 5 786 1 80ml 2 7 30 1 6 3 16 10 AM 1 1 10mg
78. 10 mg 20 mg I OH AICA HC CH Rus C H NO HCI 295 80 10 mg 1 10mg 20 mg 1 20mg 1 1 30 60mg 120mg 1 3 1 30mg 60mg 90mg 1 3
79. 35 20 CYP3A4 CYP2C8 8 9 95 B 63 4 CYP2C8 CYP3A4 14 4 1 mg 4 0 05 5 5zmol L CYP CYP1A2 CYP2C8 CYP2C9 CYP2C19 CYP2D6 CYP3A4 20 8 CYP3A4 CYP2C8 OATP1B1 1 17 1
80. FX 99 5 m 5 ga 1 1 1 x3 u 1 2 An BRL BR 43 1157 2006 3 Kaunitz AM et al Obstet Gynecol 2010 DM 7530 0001 4 9 BB 0120 106 398 MD 2007 116 625 e EE e III BEER NT a TS 4 9
81. 10 3 11 12 100 13 14 1 m 52mg 1 52mg M M T
82. 99 5 SER 66 8 3mL 100 mL 2 3 mL 100 mL 2 1 Herings R M C et al Lancet 345 1195 1995 2 EPR 3 1 Ml 4 In vitro 7651 0086 PFHFRERLETTEIESH Lilly Answers 0120 360 605 2148551 A ae 8 45 17 30 www lillyanswers jp O LY2963016 BS 18 E 1 5 29 30 0 25 mg 0 5 mg
83. a i eee 1 1 2 3 4 5 6 7 8 9 SohHELFENETNDOSSBE BE CRAMER BOSSES 1 4 AEREA RAR BROSSBE AE OSH
84. n 10 ECN Tra mean S E M 7 44 20mg21 A3ESAMBARORSLEBSAD MRPR 43 44 2 4 3 4 BE 1C 48 1 4 1
85. 2 g Clin Drug Invest 28 573 2008 13 19 KAR OBER 15 CYP 16 Niemi M et al Clin Pharmacol Ther 77 468 2005 17 Kajosaari LI et al Clin Pharmacol Ther 78 388 2005 18 Niemi M et al Diabetologia 46 347 2003 19 Skerjanec A et al 20 21 2 Eur J Clin Pharmacol 60 109 23 Bidstrup TB et al 2004 24 25 26 J Clin Pharmacol 50 205 2010
86. CYP2C8 600mg 1 2 3 3 0 25mg Cmax AUCo s 2 4 8 1 tuz 1 3 3 7 CYP3A4 100mg 1 2 3 200mg Cm AUCo s 2 8 19 ti z 6 1 2 CYP3A4 OATPIBI 100mg 2 0 25mg Cmax AUCo 1 82 2 54 tuz 36 3 Df
87. NURFW 51 Omg INDERALY Tablets 10mg II
88. 30 30 DS y E 35 gt e0 amp BS mm mm am mg mm mm _ 50 7 0 2 3 6 0 2 5 DS232 2 1 1
89. 1997 2 1 REPRE SRE RAE 1 pe ee lene 2 3 4 0 25mg 1 0 25mg 1 0 5mg 0 5mg 160 160
90. 2 3 HTA L 5 33 34 6 7 8
91. MARU MARE NAGS fn gt ET FA EE os OH NPS Pharma Japan 1 5 2 3 MEMO 1 000 5
92. 3 ee ee cw HAC OHESO DPE 4 GLP 1 SGLT2 MAO FA JIU SFY ARS B
93. DER 1 ETA HTA ee ee ree ree eee ASE O 40 mg mL O 40 mg mL HE PRIA Sa DEF A a IE 5 2 1 1
94. 48 FB EIS 285 8
95. 12 1mg n 12 248 AUC C T RSA ng h mL ng mL TET 2 48 24 8 5 3 11 4 2 7 123 8 80 4 46 9 17 1 3 12 2mg 62 5 32 6L h 24 4 3 1 1mg 4 2 2 1mg 1 3 10 5 AUCo sn ng h mL 5 n 6 35 0 7 0 31 93 5 2 12 2mg 1 3 15 9 1 9 1
96. 1 0 23 mg 1 3 0 25 0 5 mgt 1 1 mg 16 1000 8 500 FA 23 2011 2 oe Ca GI 2013 BG X TZD 2
97. e 1 gt a b c d e IIS T 3226 2 A A BD Y f A g 1 2
98. 4 2 1 2 3 AHSEFZEIL BREE PRHERDT EHE
99. AST GOT ALT GPT Al P LDH MEET EME SE ED 2 1 2 1 8
100. 1 3 142 1 1 0 1 5 0 1 2 0 1 3 AFR 0 1 S AB 0 1 8 2 2 FR OA Bob Math RAH ENTRAR BRM E 0 15 AR 0 1 DIE MIO EB BAGH HARAN A co 0 1 5 0 1
101. 4 000 5 NMO CD20 2 NMO NMO H 20
102. PID 0 2 HR PID A 8 PID 20 PID F PID 2
103. ih 2 47 48 3 100 4 BBE 5 20 6 6
104. Be 65 072 665 074 8 082 0 5mg a a 1 232041 n 32 FB5082 6525066 145 1 00 mg Ez 1 30 0 69 n 32 7 91 0 82 6 61 1 14 1 54 1 05 95 109 0 25 1mg 1 3 52 64 HbAlc NGSP 7 78 0 80 6 69 0 70 1 09 0 76 32 HbAlc NGSP 7 0 11 0 12 109 67 9 74 109 1 750mg 2250mg 2 1 0 5mg 1 3 16 HbA1c NGSP 8 HbAlc NGSP _ n 92 7 62 0 71 6
105. 6 7 J 8 1 UR ER 2
106. FER H re ad y GTP ER AAA E Mm MAB 1 RAE RE BRE EX m FRE RE Meter Rx 4 1 BAIS 1 2
107. S 2 Ethoxy 4 2 3 methyl 1 2 piperidinophenyl butylamino 2 oxoethyllbenzoic acid CH AFH Co7H36N204 452 59 29 30 31 32 33 J Diabetes Invest 3 302 2012 34 Kawamori R et al 3 36 3 38 39 40 4 2 2 w 2 gw 3 3 DPP 4 43
108. 3 HERDER F TE 4
109. 3 2 FRU VU YORE AMG CORB
110. C 4 gt 0 5 kg 4 a pmol WL pmol WL pmol L hr hr 156 40 39 39 2 0 24 0 66 78 1980 2930 119 12 0 9 7589 156 36 41 34 0 5 21 0 61 CV HED N WERE n 2 GED 3 n 154 4 n 149 ES n 155 6 n 152 2 95 80 125 sl wen mg kg min hr 0 kg 4 gt 0 5 kg 4 n mg kg min mg kg 78 2 87 2590 Ff 78 2 89 2720 au STEHE CV EN N BORER n BEER RER
111. e e e e AAD 2014 7 5 E E 025mg 0 5 90 2 v v 1 2 a 3 _ 4
112. 56 8 499 879 7 2 65 1 84 129 9 3 56 3 151 268 1 8 2
113. 1 1 88 4 52mg 1 52mg a ca 26 5 30 45 201X HO 2014 9 FP ARICA BAYER E Mirena I 5 Img 3 872549 872529 4 2014 9 ERE HIV WR B MER
114. 5 5 0 25mg Cmax AUC0 s 1 0 0 9 O DPP 4 100mg 1 1 2 2 1mg gt AUCOo 8p C T RTE ng h mL ng mL min n 12 17 75 4 05 18 62 6 77 0 51 0 05 1 32 2 n 12 18 47 6 74 19 97 8 66 0 56 0 08 1 52 0 33 EA RE eed 1 9 2 98 3 98 6 in vitro E Fi 0 01 100 ug mL BE 3 4038 gt BE CYP2C8 CYP3A4 in vitro 4C 2mg 3
115. 6 nes 4 80mL 50 S m ARMS RB ji OW Levonorgestrel JAN 13 Ethy1 17 hydroxy 18 19 dinor 17 a pregn 4 en 20 yn 3 one E C21H2802 312 45 BR 235 241 C
116. MET mer HB 1 2 BS BS 1 300 Q oR m 8 1 mg 1 A rn HEGEL UC 90 y PH MAGA WE ARNO EAN pH A Era REEH 5H gt
117. 0 91 0 50 0 82 Biz HbAlc NGSP 7 0 23 0 23 100 58 09 6 58 100 MENE 1 6 Img 1 3 5 3 1U mL gt n 6 1 3mg H n 6 1 n 6 5 8 3 mg n 6 5 8 mY CNVAFB 0 60 120 180 240 300 min 2 Goto Kakizaki 2 ATP 37 Repaglinide
118. 1 30mg 60mg 90mg 1 3 1 0 5 2mg kg 1 3 4 1 4mgkg 1 90mg 1 20 30mg 60mg 1 2 3 ARGS SIME gt i a
119. 1 I 1 1 3 1 1 ER EM 269 AAA 49 267 31 24 HbAlc 0 108 95 0 002 0 219 YD 0 4 32 HbAlc 0 020 95 0 099 0 140 Y Ch HpAlc
120. 126mg dL 1 2 200mg dL 9 GLP 1 3 CYP2C8 CYP3A4 1 Aryl 1 w a DPP 4 GLP 1 RED SGLT 2 8 SISA En gt 21 AAA SHELWF2
121. 31 071 87318219 zz 7 ag og anlegt 4 787 n 61 A a GE6 so 28 16 19 04129 07 23 02 5 ta 1 08 9 65 r 2200 18092265 17 0 0 5 a 95 105 0 25 1mg 1 3 52 HbA c NGSP 7 50 0 59 6 67 0 63 0 84 0 55 9 HbAlc NGSP 7 0 17 1 18 105 73 3 77 105 Cc 1 0 25mg 0 5mg 1mg 1 3 12 HbAic NGSP 39 HbAlc NGSP a nd RSE ga 0 18 0 61 n 32 14 077 ede a EOF 0 04 0 40 0 25mg 1 00 0 50 x
122. 0 25 mg 1 0 25 mg 0 5 mg 1 0 5 mg 1 0 25 mg 1 3 1 0 25 0 5 mg 1 1 mg 2 1 w 31 32 06 DG l 20XX X 5 2013 2 rik Hamann ZIP RAF sE 0 25mg 0 5mg LT SUREPOST 2011 3 2011 5 2011 3 2011 5
123. 1 3 3 1 30 mg 60 mg 90 mg BB L 1 3 IB 052 mg kg 1 3 4 1 mg kg 1 90 mg 4 1 20 30 mg 60 mg 1 2 3
124. 1 FA 2 5mg 1 2 3 a PsN 26 10 29 23 5 A FIT 10mg No 1 2mg 5mg 10mg No 2 40 mg mL 40 mg mL No 3 4 BS BS 9 10 No 4 carglumic acid
125. 64 0 66 0 98 0 72 1 07 0 13 Ben 1 33 0 82 i n 36 7 52 0 87 7 64 1 15 a PIHERERE Tht MRA GEHE 1 750 mg 2250mg 2 119 0 25 1mg 1 3 36 52 HbAlc NGSP 7 63 0 82 6 87 0 84 0 76 0 83 39 HbAlc NGSP 7 0 21 8 26 119 66 4 6 79 119 4 2 1 0 5mg 1 3 16 HbAIc NGSP 0 HbAlc NGSP pan Beet Pie 7 45 0 73 653 052 098 051 p
126. F G1 Fc VEGE Esta VEGF 10 BS 1 1 4 20 1 4 80
127. at ARPA n 36 250 092 on be 0 25mg n 37 6 65 0 80 i ios an 0 5mg n 36 738 0 80 6 44 063 _ vee aa 12 1mg n 37 662 065 _ 08m 95 FeO Es 1 0 5mg 90mg 1 3 16 HbAlc NGSP 39 9 ELS Bet 0 30 0 08 6 0 15 lt 0 001 a 95 4 RR fi es Ea REMY AIUD 2 A m 20 50 19 48 29 18 17 5 688 909 oo so og 7 1686 9 111822 20 006130 1013 17 819 n 61 A MEAN 49 7 lyn 64 17 61141 60 28 34 3 95 1253 28 3 78 n 61 KA e am S111 23 68 39 84
128. cs cares 1 27 0 09 1 45 1 09 lt 9 001 7 52 0 69 7 85 1 01 0 32 0 60 95 2 117 0 25 1mg 1 3 36 52 HbA c NGSP 7 63 0 88 6 66 0 57 0 97 0 70 3D HbAlc NGSP fi 7 0 23 9 28 1I7 68 4 80 I17 5 DPP 4 2 100 0 25 1mg 1 3 52 HbAlc NGSP 7 43 0 57 6 93
129. er 2m PROBST ES ROHBROR GR ERS we DEALS ES Ken AA BETA BEAT Lic amp OH ER DER BETA 4 1 II 32 268 49 Bl 2 Mm 24 376 644 43 6 7 12 1 99 11 1 7 4 0 6 5 HEHE 4 0 6 1 1 1 9 m
130. min 1041 5 Cmax AUC0 s 1 3 1 7 1 tmg 35 NMa r2 3 HEAHAR 2 0 25 Img 1 3 8 G a 79 AUCo 3h Cmax tie ng h mL ng mL min 8 79 2 12 6 28 1 68 37 17 13 67 52 324 6 408 14 76 6 48 10 34 5 40 51 13 52 14 51 03 9 7122 33 43 16 59 24 54 8 98 34 5 8 77 56 05 16 17 El n 5 2 n 6 8 1mg 500mg 55 MEL 7 Y FOCmax AUCo 1 12 89ng mL 17 11ng h mL 9 1mg 15 Cmax AUCo 13 51ng mL 16 55ng h mL 9 12 30mg 1 1
131. rzneim Forsch 34 1 4 507 1984 2 3 Cruickshank J M et al Clin Sci 59 453s 1980 4 Paterson J W et al Pharmacol Clin 2 127 1970 5 Bauer JH et al Am J Cardiol 43 860 1979 6 105 8 790 1978 7 A 96 13 910 1976 8 8 4 1267 1981 9 Cleaveland CR et al Arch Intern Med 130 47 1972 10 Coltart D J et al Br Med J 3 731 1970 11 Frohlich E D et al Circulation 37 417 1968 12 Buhler F R et al N Engl J Med 287 24 1209 1972 13 Tarazi R C et al Am J Cardiol 29 633 1972 14 Day M D et al Nature New Biol 242 30 1973 15 Adler Graschinsky E et al Br J Pharmacol 53 43 1975 16 Morales Aguilera A et al Br J Pharmacol 24 332 1965 17 Barrett A M et al Br J Pharmacol 40 373 1970 7531 0076 1 1 88 E 0120 189 115 FAX 06 6453 7376 CizHziNO HCI O AstraZeneca 1967 AstraZeneca
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