Vol. 4, No

1 0.005 71 2 0.005 72 3 0.005 73 4 0.005 74 5 0.005 KRM 75 6 0.005 76 7 0.005 77 8 0.005 78 9 0.005 79 10 0.005 80 11 0.005 TS 81 12 0.005 TOA 82 13 0.005 83 14 0.005 84 15 0.005 NS 85 16 0.005 86 17 0.005 87 18 0.005 AA 88 19 0.005 89 20 0.005 90 50 Vol. 4, No. 1 2010 61

4 69 62 Vol. 4, No. 1 2010

0.005 AA 0.005 TS 0.005 0.005 0.005 0.005 0.005 KRM 0.005 0.005 0.005 0.005 0.005 0.005 0.005 AA 0.005 0.005 TS 0.005 TOA 0.005 0.005 0.005 NS 0.005 0.005 TOA 0.005 0.005 0.005 TOA 0.005 PF 0.005 0.005 AA 0.005 0.005 50 2 2 2008 ; 2 : 196-269 3 1 2009 ; 3 : 078-108 3 2 2009 ; 3 : 172-214 Vol. 4, No. 1 2010 63

AUC Cmax 90 90= 0.05 80 125 5 90 AUC Cmax AUC Cmax 64 Vol. 4, No. 1 2010

tmax kel tmax Cmax tmax tmax kel kel tmax kel Vol. 4, No. 1 2010 65

3 1 1/10 2 4 ph1.2 ph5.5 6.5 ph6.8 7.5 1 AUC 80 5 66 Vol. 4, No. 1 2010

30 Cmax AUC 90 tmax kel 90 1 1 90 90 11190 4 ph1.2 ph5.5 6.5 ph6.8 7.5 4 ph1.2 ph5.5 6.5 ph6.8 7.5 50 rpm ph1.2 ph3.0 5.0 ph6.8 7.5 ph6.8 7.5 80 1.0 W/V 100 rpm 200 rpm 100 rpm 200 rpm 30 / 30 / Vol. 4, No. 1 2010 67

1 Cmax AUC USP 18 11 24 1124004 2008 2 50-66 68 Vol. 4, No. 1 2010

4 1 a 18 11 24 1124004 b 18 11 24 1124004 0.80 1.25 0.70 1.43 2 4 5 7 Q&A Q14 A a Vol. 4, No. 1 2010 69

b 1 c 0.80 1.25 0.80 1.25 0.70 1.43 90 0.70 1.43 d 1 2 15 mmhg 12 mmhg 3 mmhg 12 mmhg 3 mmhg 12 mmhg 15 mmhg 3 mmhg 12 mmhg 12 mmhg 3 mmhg 12 mmhg 70 Vol. 4, No. 1 2010

50 g 0.005 08AH025 0.005 a ph 0.005 b ab 90 0.70 1.43 16 1 90 mmhg - 4.58 ± 0.81-4.61 ± 0.81 1.0126 0.9932-1.0324 0-24h, mmhg h - 46.44 ± 13.75-47.73 ± 13.95 1.0312 1.0047-1.0584 tmax, h 7.31 ± 0.48 7.31 ± 0.48 a a F 5 Vol. 4, No. 1 2010 71

50 g 0.005 08AH014 0.005 a 40 0.005 b ab 90 0.80 1.25 2 2 20 1 90 mmhg 4.0 ± 0.3 4.0 ± 0.4 0.9981 0.9836 1.0128 0-23.5h, mmhg h 47.05 ± 4.52 46.67 ± 5.27 0.9903 0.9659 1.0152 72 Vol. 4, No. 1 2010

50 g 0.005 07AH011 0.005 a 0.005 b ab 90 0.70 1.43 2 2 11 1 90 mmhg 3.91 ± 1.14 3.73 ± 1.27 0.89 0.80 0.98 0-24h, mmhg h 52.09 ± 22.44 56.09 ± 27.31 0.95 0.76 1.18 Vol. 4, No. 1 2010 73

50 g 0.005 07AH020 0.005 a 80 ph 0.005 b ab 90-0.30 + 0.30 3 3 12 1 a 90 mmhg - 2.92 ± 1.51-2.90 ± 1.07 0.006-0.179 + 0.166 0-24h, mmhg h 29.90 ± 24.33 29.54 ± 21.55-0.012-0.146 + 0.121 tmax, h 10.7 ± 6.8 11.0 ± 6.8 b a b F 5 + 74 Vol. 4, No. 1 2010

50 g 0.005 07AH020 0.005 KRM a 80 ph 0.005 b ab 90-0.30 + 0.30 3 3 12 1 a 90 mmhg - 2.92 ± 1.51-2.90 ± 1.07 0.006-0.179 + 0.166 0-24h, mmhg h 29.90 ± 24.33 29.54 ± 21.55-0.012-0.146 + 0.121 tmax, h 10.7 ± 6.8 11.0 ± 6.8 b a b F 5 + Vol. 4, No. 1 2010 75

50 g 0.005 08AH004 0.005 a ph ph D- 80 0.005 b ab 90-0.30 + 0.30 3 3 14 1 a) 90 mmhg 3.5 ± 1.2 3.4 ± 1.0-0.029-0.14 0.09 0-24h, mmhg h 37.3 ± 28.5 39.3 ± 26.8 0.054-0.12 0.17 a 76 Vol. 4, No. 1 2010

50 g 0.005 08AH004 0.005 a 0.005 b ab 80 D 90-0.30 + 0.30 3 3 14 1 a) 90 mmhg 3.5 ± 1.2 3.4 ± 1.0-0.029-0.14 0.09 0-24h, mmhg h 37.3 ± 28.5 39.3 ± 26.8 0.054-0.12 0.17 a Vol. 4, No. 1 2010 77

50 g 0.005 07AH051 0.005 a 80 50 ph 0.005 b ab 90 0.70 1.43 2 2 19 1 90 mmhg 4.61 ± 1.67 4.73 ± 1.27 1.057 0.929-1.203 0-22h, mmhg h 32.78 ± 15.02 32.56 ± 14.71 1.018 0.841-1.233 tmax, h 9.47 ± 2.48 9.26 ± 3.00 a a F 5.. 78 Vol. 4, No. 1 2010

50 g 07AH052 0.005 a 0.005 b ab 90-0.20 + 0.20 8 25 µl a 90 mmhg 9.78 ± 2.61 9.95 ± 2.25 0.02-0.10 0.13 0-24h, mmhg h 188.89 ± 46.86 192.43 ± 33.27 0.02-0.11 0.14 a 2010 63 435-40 Vol. 4, No. 1 2010 79

50 g 0.005 07AH051 0.005 a 80 50 0.005 b ab 90 0.70 1.43 2 2 19 1 90 mmhg 4.61 ± 1.67 4.73 ± 1.27 1.057 0.929-1.203 0-22h, mmhg h 32.78 ± 15.02 32.56 ± 14.71 1.018 0.841-1.233 tmax, h 9.47 ± 2.48 9.26 ± 3.00 a a F 5.. 80 Vol. 4, No. 1 2010

50 g 0.005 08AH004 0.005 TS a 80 ph ph D- 0.005 b ab 90-0.30 + 0.30 3 3 14 1 a) 90 mmhg 3.5 ± 1.2 3.4 ± 1.0-0.029-0.14 0.09 0-24h, mmhg h 37.3 ± 28.5 39.3 ± 26.8 0.054-0.12 0.17 a Vol. 4, No. 1 2010 81

50 g 0.005 07AH051 0.005 TOA a 80 50 ph 0.005 b ab 90 0.70 1.43 2 2 19 1 90 mmhg 4.61 ± 1.67 4.73 ± 1.27 1.057 0.929-1.203 0-22h, mmhg h 32.78 ± 15.02 32.56 ± 14.71 1.018 0.841-1.233 tmax, h 9.47 ± 2.48 9.26 ± 3.00 a a F 5.. 82 Vol. 4, No. 1 2010

50 g 0.005 06AH006 0.005 a 80 ph 0.005 b ab 90 0.70 1.43 2 2 23 1 90 mmhg 2.86 ± 1.20 2.91 ± 1.11 1.0324 0.8606-1.2385-1-23h, mmhg h 29.85 ± 22.75 26.72 ± 17.18 0.9156 0.7009-1.1960 tmax, h 8.9 ± 2.3 9.1 ± 3.7 a a 5 Vol. 4, No. 1 2010 83

50 g 0.005 07AH051 0.005 a 80 ph 0.005 b ab 90 0.70 1.43 2 2 19 1 90 mmhg 4.61 ± 1.67 4.73 ± 1.27 1.057 0.929-1.203 0-22h, mmhg h 32.78 ± 15.02 32.56 ± 14.71 1.018 0.841-1.233 tmax, h 9.47 ± 2.48 9.26 ± 3.00 a a F 5.. 84 Vol. 4, No. 1 2010

50 g 0.005 08AH014 0.005 NS a 40 0.005 b ab 90 0.70 1.43 2 2 20 1 90 mmhg 4.0 ± 0.3 4.0 ± 0.4 0.9981 0.9836 1.0128 0-23.5h, mmhg h 47.05 ± 4.52 46.67 ± 5.27 0.9903 0.9659 1.0152 Vol. 4, No. 1 2010 85

50 g 0.005 06AH006 0.005 a 0.005 b ab 80 ph 90 0.70 1.43 2 2 23 1 90 mmhg 2.86 ± 1.20 2.91 ± 1.11 1.0324 0.8606-1.2385-1-23h, mmhg h 29.85 ± 22.75 26.72 ± 17.18 0.9156 0.7009-1.1960 tmax, h 8.9 ± 2.3 9.1 ± 3.7 a a 5 86 Vol. 4, No. 1 2010

50 g 0.005 07AH051 0.005 a 0.005 b ab 80 50 ph 90 0.70 1.43 2 2 19 1 90 mmhg 4.61 ± 1.67 4.73 ± 1.27 1.057 0.929-1.203 0-22h, mmhg h 32.78 ± 15.02 32.56 ± 14.71 1.018 0.841-1.233 tmax, h 9.47 ± 2.48 9.26 ± 3.00 a a F 5.. Vol. 4, No. 1 2010 87

50 g 0.005 08AH025 0.005 AA a ph 0.005 b ab 90 0.70 1.43 16 1 90 mmhg - 4.58 ± 0.81-4.61 ± 0.81 1.0126 0.9932-1.0324 0-24h, mmhg h - 46.44 ± 13.75-47.73 ± 13.95 1.0312 1.0047-1.0584 tmax, h 7.31 ± 0.48 7.31 ± 0.48 a a F 5 88 Vol. 4, No. 1 2010

50 g 0.005 07AH051 0.005 a 0.005 b ab 80 50 ph 90 0.70 1.43 2 2 19 1 90 mmhg 4.61 ± 1.67 4.73 ± 1.27 1.057 0.929-1.203 0-22h, mmhg h 32.78 ± 15.02 32.56 ± 14.71 1.018 0.841-1.233 tmax, h 9.47 ± 2.48 9.26 ± 3.00 a a F 5.. Vol. 4, No. 1 2010 89

50 g 0.005 07AH011 0.005 a 0.005 b ab 90 0.70 1.43 2 2 11 1 90 mmhg 3.91 ± 1.14 3.73 ± 1.27 0.89 0.80 0.98 0-24h, mmhg h 52.09 ± 22.44 56.09 ± 27.31 0.95 0.76 1.18 90 Vol. 4, No. 1 2010