(µg/ml) No.4 No.5 No.6 Mean S

(1)

Table 7 Ferulic acid 在家兔血漿中定量分析之回收率(Recovery)試驗 Recovery Test Spiked conc.

(µg/ml)

Ferulic acid

in plasma

Ferulic acid

in methanol

Recovery (%)

100 347.80±10.29 350.601±7.126 98.54±0.670

50 179.56±3.02 180.392±0.759 99.08±1.397

30 101.93±5.09 105.584±1.900 94.45±3.320

10 35.714±1.470 37.469±3.415 91.31±6.193

5 17.407±0.214 17.961±0.632 96.97±2.632

3 10.752±0.416 11.094±0.357 94.13±2.891

1 3.580±0.055 3.586±0.043 98.21±0.631

0.5 1.647±0.057 1.678±0.059 94.17±0.300

0.1 0.336±0.008 0.342±0.007 96.17±0.772

0.05 0.177±0.004 0.181±0.007 95.16±0.452

Mean ^95.79%

S.D. ^0.023

C.V. ^2.43

(2)

Table 8 Ferulic acid 在家兔血漿中之同日內(Intraday)精確性試驗

No.1 No.2 No.3 Spiked

Conc.

(µg/ml) No.4 No.5 No.6

Mean S. D. C.V.(%)

100.534 101.754 99.954 100

99.752 98.753 98.452 99.867 1.101 1.10 49.956 52.171 50.119

50

50.732 51.432 49.153 50.594 0.993 1.96 30.457 29.753 30.952

30

31.254 28.453 29.754 30.104 0.925 3.07 10.429 10.415 9.973

10 9.752 9.854 10.542 10.161 0.310 3.06 4.579 5.124 4.849

5 4.987 5.043 4.852 4.906 0.176 3.59 2.752 3.129 3.043

3

2.964 2.997 2.952 2.973 0.115 3.86 1.013 1.056 0.980

1

1.075 1.075 0.973 1.029 0.042 4.12 0.515 0.473 0.483

0.5

0.525 0.483 0.472 0.492 0.021 4.18 0.103 0.108 0.108

0.1 0.094 0.099 0.098 0.102 0.005 5.10 0.055 0.052 0.054

0.05

0.051 0.046 0.047 0.051 0.003 6.57

(3)

Table 9 Ferulic acid 在家兔血漿中之間日內(Interday)精確性試驗

No.1 No.2 No.3 Spiked

Conc.

(µg/ml) No.4 No.5 No.6

Mean S. D. C.V.(%)

99.752 100.432 100.532

100 98.751 97.453 99.543 99.411 1.057 1.06 50.290 48.609 49.422

50 49.752 48.892 48.753 49.286 0.597 1.21 29.953 28.754 30.543

30 30.321 29.752 28.743 29.678 0.704 2.37 10.378 10.119 10.541

10 9.985 9.845 9.914 10.130 0.251 2.48 5.212 5.254 4.974

5 4.953 4.953 4.997 5.057 0.126 2.49 3.114 3.049 2.897

3 2.859 2.953 2.997 2.978 0.087 2.92 1.001 0.988 1.079

1 0.997 0.978 0.991 1.006 0.034 3.34 0.499 0.474 0.530

0.5 0.489 0.485 0.513 0.498 0.019 3.73 0.108 0.095 0.097

0.1 0.105 0.103 0.092 0.100 0.006 5.72 0.047 0.053 0.049

0.05 0.052 0.056 0.048 0.051 0.003 6.20

(4)

Table 10 Ferulic acid 定量的極限試驗(Limit of Quantitation)

1 2 3

Spiked Conc.

(µg/ml) ⁴ ⁵ ⁶

Mean S.D. C.V.%

100.764 97.942 102.638

100 100.450 99.753 99.854 100.234 1.399 1.40 48.618 48.875 48.753

50 49.519 50.345 50.437 49.425 0.740 1.50 29.543 29.531 30.455

30 28.743 30.157 28.592 29.504 0.676 2.29 9.753 9.854 9.779

10 10.325 10.154 10.254 10.020 0.232 2.31 4.975 4.854 4.954

5 4.853 5.217 5.043 4.983 0.124 2.50 2.945 3.152 3.045

3 2.853 3.043 2.897 2.989 0.101 3.39 1.047 0.944 0.936

1 0.989 0.937 0.989 0.974 0.040 4.08 0.482 0.489 0.478

0.5 0.522 0.474 0.529 0.496 0.022 4.37 0.092 0.094 0.100

0.1 0.092 0.108 0.102 0.098 0.006 6.01 0.044 0.044 0.050

0.05

0.047 0.058 0.051 0.049 0.005 9.86

(5)

Table 11 Ferulic acid 在家兔血漿中於 25℃之安定性試驗

Time 0.05 µg/ml 1 µg/ml 100 µg/ml

0-hr 0.051±0.0024 1.005±0.0274 100.451±0.7720 1-hr 0.048±0.0022 1.032±0.0202 99.653±0.1410 3-hr 0.051±0.0025 0.988±0.0291 99.860±0.0731 6-hr 0.050±0.0027 0.984±0.0218 99.778±0.2542 12-hr 0.052±0.0022 0.990±0.0080 99.903±0.6027 24-hr 0.049±0.0010 0.993±0.0052 99.749±0.3569 36-hr 0.049±0.0009 0.968±0.0166 99.680±0.8393

Table 12 Ferulic acid 在家兔血漿中於 -30℃之安定性試驗 Time 0.05 µg/ml 1 µg/ml 100 µg/ml

0-day 0.0504±0.0017 1.0307±0.0262 100.407±0.8019 1-day 0.0509±0.0009 0.9990±0.0046 100.044±0.3458 3-day 0.0512±0.0014 0.9960±0.0009 99.051±1.2207 6-day 0.0500±0.0010 0.9946±0.0076 99.714±0.1975 10-day 0.0495±0.0011 0.9914±0.0057 99.566±0.1298 15-day 0.0490±0.0005 0.9820±0.0055 98.983±0.6875

(6)

Table 13 六隻家兔靜脈注射 2 mg/kg 之 Ferulic acid 標準品後血中濃度值(µg/ml)

Time (min.)

No.1 No.2 No.3 No.4 No.5 No.6 Mean S.D.

2.5 5.235 4.777 5.577 5.257 6.695 5.806 5.558 0.657

5 3.832 4.094 4.226 3.771 4.419 4.035 4.063 0.242

10 1.860 2.039 2.088 1.998 2.803 1.802 2.098 0.362

15 1.047 1.223 1.195 1.146 1.514 1.089 1.202 0.166

20 0.774 0.904 0.765 0.721 0.804 0.665 0.772 0.081

30 0.493 0.620 0.453 0.468 0.465 0.397 0.483 0.074

45 0.368 0.394 0.305 0.344 0.289 0.281 0.330 0.046

60 0.189 0.217 0.179 0.191 0.237 0.163 0.196 0.027

75 0.135 0.112 0.125 0.141 0.179 0.112 0.134 0.025

90 0.096 0.081 0.089 0.094 0.117 0.085 0.094 0.013

105 0.069 0.068 0.062 0.064 0.094 0.065 0.070 0.012

120 0.053 0.050 0.052 0.055 0.064 0.051 0.054 0.005

(7)

Time (min..)

2.5 21.956 22.948 20.681 27.195 23.614 23.016 23.235 2.005

5 19.991 21.791 15.895 23.019 18.624 18.926 19.708 2.299

10 11.057 13.453 9.534 13.981 12.013 12.137 12.029 1.473

15 7.813 8.542 5.438 7.366 8.102 8.938 7.700 1.129

20 5.492 5.417 3.894 5.635 4.782 5.175 5.066 0.591

30 2.569 3.618 2.126 3.412 2.716 2.982 2.904 0.504

45 1.684 2.219 1.113 1.845 1.469 1.589 1.653 0.339

60 0.851 1.176 0.698 1.075 0.837 0.912 0.925 0.158

75 0.518 0.618 0.486 0.639 0.407 0.516 0.531 0.079

90 0.326 0.419 0.351 0.357 0.286 0.257 0.333 0.052

105 0.215 0.285 0.224 0.265 0.199 0.178 0.228 0.037

120 0.164 0.186 0.169 0.211 0.156 0.128 0.169 0.026

150 0.087 0.098 0.083 0.124 0.081 0.091 0.094 0.015

180 0.051 0.055 0.053 0.073 0.051 0.054 0.056 0.008

(8)

Time (min.)

2.5 95.396 84.926 90.053 93.583 97.528 88.027 91.586 4.758

5 81.627 72.187 79.055 84.031 88.472 81.692 81.177 5.425

10 60.964 51.045 53.039 57.041 63.466 57.913 57.245 4.672

15 35.269 31.329 36.292 35.338 41.476 38.791 36.416 3.453

20 28.264 23.681 27.681 28.467 29.302 29.905 27.883 2.204

30 14.943 12.168 14.106 15.071 18.253 17.508 15.342 2.236

45 7.968 6.286 7.567 8.135 9.437 9.459 8.142 1.201

60 4.209 3.439 4.031 4.281 4.726 5.238 4.321 0.613

75 2.021 1.542 1.907 2.856 2.531 3.148 2.334 0.613

90 1.538 1.035 1.541 1.892 1.341 2.132 1.580 0.390

105 1.076 0.791 1.058 1.349 0.959 1.371 1.101 0.225

120 0.743 0.576 0.715 0.843 0.740 0.937 0.759 0.122

150 0.438 0.379 0.448 0.447 0.461 0.498 0.445 0.039

180 0.238 0.205 0.299 0.278 0.302 0.315 0.273 0.043

210 0.128 0.116 0.166 0.149 0.181 0.186 0.154 0.028

240 0.081 0.075 0.091 0.084 0.099 0.103 0.089 0.011

270 0.053 0.051 0.058 0.055 0.052 0.068 0.056 0.006

(9)

Table 16 六隻家兔靜脈注射不同劑量之 Ferulic acid 標準品後平均血中濃度值(µg/ml)

Dose Time

(min.) 2 mg/kg 10 mg/kg 50 mg/kg 2.5 ^5.558±^0.657 ^23.235±^2.005 ^91.586±^4.758

5 4.063 ±^0.242 ^19.708±^2.299 ^81.177±^5.425 10 ^2.098±^0.362 ^12.029±^1.473 ^57.245±^4.672 15 ^1.202±^0.166 ^7.700±^1.129 ^36.416±^3.453 20 0.772 ±^0.081 ^5.066±^0.591 ^27.883±^2.204 30 ^0.483±^0.074 ^2.904±^0.504 ^15.342±^2.236 45 ^0.330±^0.046 ^1.653±^0.339 ^8.142±^1.201 60 0.196 ±^0.027 ^0.925±^0.158 ^4.321±^0.613 75 ^0.134±^0.025 ^0.531±^0.079 ^2.334±^0.613 90 ^0.094±^0.013 ^0.333±^0.052 ^1.580±^0.390 105 0.070 ±^0.012 ^0.228±^0.037 ^1.101±^0.225 120 ^0.054±^0.005 ^0.169±^0.026 ^0.759±^0.122 150 N.D. ^0.094±^0.015 ^0.445±^0.039 180 N.D. 0.056 ±^0.008 ^0.273±^0.043

210 N.D. N.D. ^0.154±^0.028

240 N.D. N.D. ^0.089±^0.011

270 N.D. N.D. 0.056 ±^0.006

※ Data are expressed as Mean ± S.D.

※ N.D. are expressed as not detectable

(10)

Table 17 六隻家兔靜脈注射 2 mg/kg 之 Ferulic acid 標準品後血中濃度值(µg/ml)經 LAGRAN-P 程式處理之相關藥動學參數 Parametrs No. 1 No. 2 No. 3 No. 4 No.5 No.6 Mean S.D.

AUCp (µg.min/ml) 58.994 64.467 60.579 58.698 69.656 55.659 61.342 4.985

AUCtotal(µg.min/ml) 61.467 66.650 63.037 61.214 72.598 58.326 63.882 5.063

Cl (l/min) 0.033 0.030 0.032 0.033 0.028 0.032 0.031 0.002

λ-z (min^-1) 0.021 0.023 0.021 0.022 0.022 0.020 0.022 0.001

T_1/2(min.) 32.342 30.264 32.756 31.695 31.863 32.013 31.822 0.851

VDss (l) 0.971 0.841 0.886 0.968 0.802 0.919 0.898 0.068

MRT (min) 29.836 28.024 27.910 29.626 29.100 29.047 28.924 0.801

※ 各藥動學參數說明請參閱附錄一

Table 18 六隻家兔靜脈注射 10 mg/kg 之 Ferulic acid 標準品後血中濃度值(µg/ml)經 LAGRAN-P 程式處理之相關藥動學參數 Parametrs No. 1 No.2 No.3 No. 4 No.5 No. 6 Mean S.D.

AUCp (µg.min/ml) 324.409 378.423 258.820 376.577 314.668 329.890 330.47 44.38

Cl (l/min) 0.031 0.026 0.038 0.027 0.032 0.030 0.031 0.004

λ-z (min^-1) 0.019 0.020 0.019 0.019 0.019 0.020 0.019 0.001

T1/2(min.) 35.598 34.126 36.042 35.175 36.079 35.200 35.370 0.724

VDss (l) 0.768 0.684 1.021 0.694 0.773 0.743 0.781 0.123

MRT (min) 25.106 26.078 26.698 25.403 24.541 24.702 25.421 0.831

(11)

Table 19 六隻家兔靜脈注射 50 mg/kg 之 Ferulic acid 標準品後血中濃度值(µg/ml)經 LAGRAN-P 程式處理之相關藥動學參數 Parametrs No. 1 No. 2 No. 3 No. 4 No. 5 No. 6 Mean S.D.

AUCp (µg.min/ml) 1568.9 1321.8 1496.9 1593.0 1727.4 1690.4 1566.4 146.1

Cl (l/min) 0.032 0.038 0.033 0.031 0.029 0.030 0.032 0.003

λ-z (min^-1) 0.018 0.017 0.017 0.017 0.018 0.017 0.017 0.001

T_1/2(min.) 38.529 41.459 40.584 41.721 39.538 39.610 40.240 1.234

VDss (l) 0.817 0.945 0.884 0.846 0.752 0.841 0.848 0.065

MRT (min) 25.696 25.047 26.512 27.020 26.033 28.484 26.465 1.198

(12)

Table 20 六隻家兔靜脈注射 2 mg/kg 之 Ferulic acid 標準品後血中濃度值(µg/ml)經 WINNOLIN 程式處理之相關藥動學參數

Parametrs No. 1 No. 2 No. 3 No. 4 No. 5 No. 6 Mean S.D.

A(µg/ml) 6.933 5.890 7.395 6.809 8.514 8.117 7.276 0.950

B(µg/ml) 0.780 0.781 0.555 0.725 0.653 0.690 0.697 0.086

α^(min^-1⁾ 0.168 0.133 0.147 0.158 0.144 0.179 0.155 0.017

β^(min^-1⁾ 0.022 0.021 0.019 0.021 0.019 0.023 0.021 0.002

AUC(µg.min/ml) 77.597 80.555 80.424 77.463 94.000 76.038 81.013 6.607

K10-HL(min) 6.973 8.369 7.011 7.128 7.108 5.984 7.096 0.759

α-HL(min) 4.132 5.198 4.730 4.387 4.803 3.878 4.521 0.483

β-HL(min) 32.216 32.273 37.394 32.875 37.168 30.759 33.781 2.800

K10(min) 0.099 0.083 0.099 0.097 0.098 0.116 0.099 0.010

K12(min) 0.054 0.037 0.039 0.048 0.038 0.051 0.044 0.007

K21(min) 0.036 0.035 0.027 0.034 0.028 0.035 0.032 0.004

Volume(l) 0.570 0.600 0.579 0.611 0.567 0.545 0.579 0.024

Cmax(µg./ml) 7.714 6.672 7.951 7.533 9.167 8.808 7.974 0.903

Cl(l/min) 0.057 0.050 0.057 0.059 0.055 0.063 0.057 0.004

MRT(min) 24.899 25.141 24.379 24.565 24.316 21.214 24.086 1.441

VDss(l) 1.412 1.248 1.394 1.459 1.345 1.339 1.366 0.073

(13)

Table 21 六隻家兔靜脈注射 10 mg/kg 之 Ferulic acid 標準品後血中濃度值(µg/ml)經 WINNOLIN 程式處理之相關藥動學參數 Parametrs No. 1 No. 2 No. 3 No. 4 No. 5 No. 6 Mean S.D.

A(µg/ml) 26.219 27.355 24.727 32.894 26.826 25.738 27.293 2.638

B(µg/ml) 2.354 2.457 2.811 3.099 3.093 2.977 2.799 0.296

α^(min^-1⁾ ^0.097 ^0.089 ^0.124 ^0.110 ^0.104 ^0.094 0.103 0.012

β^(min^-1⁾ ^0.020 ^0.018 ^0.023 ^0.020 ^0.024 ^0.024 0.021 0.002

AUC(µg.min/ml) 390.400 448.328 320.714 456.416 384.843 398.946 399.941 44.959

K10-HL(min) 9.471 10.424 8.073 8.790 8.916 9.630 9.217 0.739

α-HL(min) 7.182 7.809 5.570 6.329 6.679 7.352 6.820 0.732

β-HL(min) 34.966 39.544 30.087 34.901 28.316 29.317 32.855 3.962

K10(min) 0.073 0.066 0.086 0.079 0.078 0.072 0.076 0.006

K12(min) 0.017 0.016 0.028 0.023 0.018 0.015 0.020 0.005

K21(min) 0.026 0.023 0.033 0.028 0.033 0.031 0.029 0.004

Volume(l) 0.770 0.738 0.726 0.833 0.802 0.801 0.778 0.038

Cmax(µg./ml) 28.573 29.811 27.538 35.993 29.919 28.716 30.092 2.759

Cl(l/min) 0.056 0.049 0.062 0.066 0.062 0.058 0.059 0.005

MRT(min) 22.551 25.579 21.492 23.225 19.885 20.610 22.224 1.870

VDss(l) 1.271 1.255 1.340 1.527 1.240 1.188 1.304 0.109

(14)

Table 22 六隻家兔靜脈注射 50 mg/kg 之 Ferulic acid 標準品後血中濃度值(µg/ml)經 WINNOLIN 程式處理之相關藥動學參數 Parametrs No. 1 No. 2 No. 3 No. 4 No. 5 No. 6 Mean S.D.

A(µg/ml) 108.61 97.64 100.74 106.41 110.05 97.45 103.48 5.586

B(µg/ml) 7.812 6.680 9.526 9.852 9.281 9.856 8.835 1.300

α^(min^-1⁾ 0.078 0.081 0.079 0.081 0.073 0.070 0.077 0.004

β^(min^-1⁾ 0.018 0.019 0.020 0.018 0.019 0.018 0.019 0.001

AUC(µg.min/ml) 1832.8 1557.6 1751.7 1856.0 1989.5 1937.4 1820.8 153.3

K10-HL(min) 10.912 10.350 11.012 11.065 11.556 12.514 11.235 0.736

α-HL(min) 8.915 8.527 8.736 8.577 9.514 9.835 9.017 0.536

β-HL(min) 38.680 36.997 35.074 37.935 35.768 39.010 37.244 1.588

K10(min) 0.064 0.067 0.063 0.063 0.060 0.055 0.062 0.004

K12(min) 0.010 0.010 0.011 0.013 0.009 0.010 0.011 0.001

K21(min) 0.022 0.023 0.025 0.024 0.024 0.023 0.023 0.001

Volume(l) 1.031 0.959 0.998 0.989 1.048 1.025 1.008 0.032

Cmax(µg./ml) 116.42 104.32 110.26 116.27 119.33 107.31 112.32 5.914

Cl(l/min) 0.065 0.064 0.063 0.062 0.063 0.057 0.062 0.003

MRT(min) 23.075 21.704 23.060 24.679 22.844 26.239 23.600 1.604

VDss(l) 1.511 1.393 1.448 1.529 1.435 1.490 1.468 0.051

(15)

Table 23 生體可用率實驗中六隻家兔靜脈注射 50 mg/kg 之 Ferulic acid 標準品後血中濃度值(µg/ml)

Time (mim.)

No. 1 No. 2 No. 3 No. 4 No. 5 No. 6 Mean S.D.

5 71.416 64.391 80.268 68.201 74.391 75.627 72.382 5.640

10 60.794 51.093 65.268 51.093 59.529 64.375 58.692 6.263

15 42.076 34.268 51.971 39.407 44.761 49.017 43.583 6.446

20 33.615 26.716 38.465 28.681 31.684 35.946 32.518 4.414

30 21.706 16.432 26.947 16.039 19.384 23.036 20.591 4.174

45 12.169 8.139 15.136 8.943 11.096 14.735 11.703 2.894

60 5.468 3.567 7.056 3.675 5.586 7.239 5.432 1.581

90 1.891 1.973 2.961 1.387 2.173 2.712 2.183 0.574

120 0.854 0.801 1.394 0.611 0.805 1.171 0.939 0.287

150 0.386 0.436 0.735 0.391 0.489 0.672 0.518 0.150

180 0.192 0.231 0.367 0.219 0.248 0.391 0.275 0.083

210 0.126 0.141 0.180 0.147 0.162 0.188 0.157 0.024

240 0.079 0.083 0.102 0.087 0.095 0.117 0.094 0.014

270 0.053 0.057 0.066 0.054 0.063 0.073 0.061 0.008

(16)

Table 24 生體可用率實驗中六隻家兔肌肉注射 50 mg/kg 之 Ferulic acid 標準品後血中濃度值(µg/ml)

Time (min.)

5 15.462 16.981 14.265 12.187 16.273 14.265 14.906 1.715

10 23.976 24.297 20.923 19.156 21.596 20.923 21.812 1.977

15 27.905 29.156 32.245 23.195 25.534 32.245 28.380 3.625

20 24.638 25.219 30.298 20.597 23.738 30.298 25.798 3.833

30 20.519 23.518 23.795 16.518 18.437 23.795 21.097 3.124

45 11.652 14.594 15.268 11.056 12.318 15.268 13.359 1.903

60 7.462 8.139 9.417 6.518 6.792 9.417 7.958 1.262

90 3.019 4.352 5.538 2.957 3.324 5.538 4.121 1.206

120 1.235 2.038 2.288 1.654 1.712 2.288 1.869 0.413

150 0.579 0.894 0.915 0.786 0.972 0.915 0.844 0.143

180 0.387 0.476 0.401 0.361 0.531 0.401 0.426 0.064

210 0.221 0.283 0.205 0.234 0.289 0.205 0.240 0.038

240 0.134 0.161 0.135 0.139 0.168 0.135 0.145 0.015

270 0.086 0.094 0.076 0.087 0.102 0.076 0.087 0.010

300 0.053 0.059 0.051 0.054 0.065 0.051 0.056 0.006

(17)

Table 25 生體可用率實驗中六隻家兔口服投與 100 mg/kg 之 Ferulic acid 標準品後血中濃度值(µg/ml)

Time (min.)

10 11.298 10.213 13.289 9.856 8.372 15.647 11.446 2.629

20 15.462 14.234 18.628 13.569 12.681 18.598 15.529 2.556

30 17.795 16.058 20.428 15.309 14.697 21.168 17.576 2.714

45 11.089 10.463 14.359 11.639 10.289 15.106 12.158 2.065

60 8.657 7.641 10.126 8.128 7.913 10.694 8.860 1.259

90 4.798 4.139 5.547 4.479 5.078 5.139 4.863 0.503

120 2.038 2.467 3.561 3.056 2.973 2.654 2.792 0.527

150 1.058 1.297 1.741 1.541 1.453 1.216 1.384 0.245

180 0.549 0.615 0.906 0.813 0.763 0.726 0.729 0.130

210 0.394 0.376 0.534 0.431 0.312 0.386 0.406 0.074

240 0.245 0.268 0.336 0.296 0.231 0.261 0.273 0.038

270 0.147 0.149 0.206 0.165 0.139 0.159 0.161 0.024

300 0.099 0.094 0.131 0.107 0.094 0.102 0.105 0.014

360 0.051 0.051 0.059 0.054 0.052 0.053 0.053 0.003

(18)

Table 26 生體可用率實驗中六隻家兔靜脈注射、肌肉注射及口服投與 Ferulic acid 標準品後之平均血中濃度值(µg/ml)

Time (min.)

I.V.

(50 mg/kg)

I.M.

(50 mg/kg)

P.O.

(100 mg/kg) 5 ^72.382 ± 5.640 14.906 ± ^1.715 -

10 58.692 ± 6.263 21.812 ± 1.977 11.446 ±^2.629 15 ^43.583 ± 6.446 28.380 ± ^3.625 -

20 ^32.518 ± 4.414 25.798 ± 3.833 15.529 ± ^2.556 30 20.591 ± 4.174 21.097 ± 3.124 17.576 ± ^2.714 45 ^11.703 ± 2.894 13.359 ± 1.903 12.158 ± ^2.065 60 ^5.432 ± 1.581 7.958 ± 1.262 8.860 ± ^1.259 90 2.183 ± 0.574 4.121 ± 1.206 4.863 ± ^0.503 120 ^0.939 ± 0.287 1.869 ± 0.413 2.792 ± ^0.527 150 ^0.518 ± 0.150 0.844 ± 0.143 1.384 ± ^0.245 180 0.275 ± 0.083 0.426 ± 0.064 0.729 ± ^0.130 210 ^0.157 ± 0.024 0.240 ± 0.038 0.406 ± ^0.074 240 ^0.094 ± 0.014 0.145 ± 0.015 0.273 ± ^0.038 270 0.061 ± 0.008 0.087 ± 0.010 0.161 ± ^0.024 300 N.D. ^0.056 ± 0.006 0.105 ± ^0.014

360 N.D. N.D. ^0.053 ± ^0.003

※ Data are expressed as Mean ± S.D.

※ N.D. are expressed as not detectable

(19)

Table 27 生體可用率實驗中六隻家兔靜脈注射 50 mg/kg 之 Ferulic acid 標準品後血中濃度值(µg/ml)經 LAGRAN-P 程式處理之相關藥動學參數

AUCp (µg.min/ml) 1583.3 1264.7 1911.9 1293.4 1549.6 1802.0 1567.5 261.2

Cl (l/min) 0.032 0.039 0.026 0.039 0.032 0.028 0.033 0.005

λ-z (min^-1) 0.018 0.018 0.019 0.016 0.017 0.019 0.018 0.001

T_1/2(min.) 38.140 38.945 36.377 42.709 40.247 36.653 38.845 2.379

VDss (l) 0.970 1.246 0.881 1.156 1.021 0.939 1.036 0.139

MRT (min) 30.775 31.603 33.751 29.974 31.729 33.905 31.956 1.582

Table 28 生體可用率實驗中六隻家兔肌肉注射 50 mg/kg 之 Ferulic acid 標準品後血中濃度值(µg/ml)經 LAGRAN-P 程式處理之相關藥動學參數

AUCp (µg.min/ml) 1234.5 1419.8 1528.8 1085.0 1214.1 1528.8 1335.2 184.1

Cl (l/min) 0.040 0.035 0.033 0.046 0.041 0.033 0.038 0.005

λ ^-1

(20)

Table 29 生體可用率實驗中六隻家兔口服投與 100 mg/kg 之 Ferulic acid 標準品後血中濃度值(µg/ml)經 LAGRAN-P 程式處理之相關藥動學參數

AUCp (µg.min/ml) 1073.0 1002.6 1335.6 1056.4 1015.7 1306.5 1131.6 149.2

Cl (l/min) 0.093 0.099 0.075 0.094 0.098 0.076 0.089 0.011

λ-z (min^-1) 0.012 0.012 0.014 0.012 0.011 0.012 0.012 0.001

T_1/2(min.) 59.428 59.401 50.191 56.498 64.323 57.646 57.914 4.632

VDss (l) 5.777 6.448 4.892 6.439 6.738 4.628 5.820 0.884

MRT (min) 62.244 64.936 65.541 68.307 68.762 60.665 65.076 3.217

(21)

Table 30 生體可用率實驗中六隻家兔靜脈注射 50 mg/kg 之 Ferulic acid 標準品後血中濃度值(µg/ml)經 WINNOLIN 程式處理之相關藥動學參數

A(µg/ml) 86.202 80.453 91.099 86.095 91.113 88.751 87.285 4.015

B(µg/ml) 7.524 7.877 10.956 5.319 8.698 9.692 8.344 1.939

α^(min^-1⁾ 0.053 0.065 0.050 0.061 0.060 0.052 0.057 0.006

β^(min^-1⁾ 0.019 0.019 0.019 0.018 0.018 0.018 0.019 0.001

AUC(µg.min/ml) 2002.2 1653.2 2383.0 1708.0 2004.3 2251.8 2000.420 288.324

K10-HL(min) 14.807 12.973 16.185 12.951 13.919 15.855 14.448 1.402

α-HL(min) 12.989 10.631 13.796 11.354 11.618 13.426 12.302 1.275

β-HL(min) 35.640 36.891 36.045 38.798 38.028 38.100 37.250 1.257

K10(min) 0.047 0.053 0.043 0.054 0.050 0.044 0.048 0.005

K12(min) 0.004 0.008 0.004 0.005 0.006 0.005 0.005 0.001

K21(min) 0.022 0.023 0.023 0.020 0.022 0.021 0.022 0.001

Volume(l) 1.174 1.132 1.178 1.149 1.102 1.219 1.159 0.041

Cmax(µg./ml) 93.725 88.330 102.055 91.414 99.811 98.444 95.630 5.317

Cl(l/min) 0.055 0.060 0.051 0.061 0.055 0.053 0.056 0.006

MRT(min) 25.053 24.945 27.578 23.283 25.832 27.792 25.747 1.717

VDss(l) 1.376 1.509 1.273 1.431 1.418 1.481 1.415 0.084

(22)

Table 31 生體可用率實驗中六隻家兔肌肉注射 50 mg/kg 之 Ferulic acid 標準品後血中濃度值(µg/ml)經 WINNOLIN 程式處理之相關藥動學參數

A(µg/ml) 286.686 144.147 234.752 372.962 361.867 234.752 272.528 86.723

B(µg/ml) 7.079 11.805 9.030 7.353 11.438 9.030 9.289 1.985

α^(min^-1⁾ ^0.075 ^0.079 ^0.066 ^0.071 ^0.077 ^0.066 ^0.072 ^0.005 β^(min^-1⁾ ^0.060 ^0.052 ^0.050 ^0.062 ^0.067 ^0.050 ^0.057 ^0.007 AUC(µg.min/ml) 0.016 0.017 0.016 0.015 0.017 0.016 0.016 0.001

K10-HL(min) 0.048 0.040 0.041 0.045 0.045 0.041 0.043 0.003

α-HL(min) 0.008 0.007 0.005 0.011 0.014 0.005 0.008 0.003

β-HL(min) 0.020 0.023 0.020 0.020 0.024 0.020 0.021 0.002

K10(min) 1282.336 1458.207 1566.013 1139.950 1271.216 1566.013 1380.623 175.677

K12(min) 14.456 17.457 16.840 15.271 15.336 16.840 16.033 1.173

K21(min) 9.269 8.790 10.427 9.823 9.009 10.427 9.624 0.711

Volume(l) 11.515 13.276 13.822 11.202 10.403 13.822 12.340 1.483

Cmax(µg./ml) 43.897 39.625 42.394 47.333 41.960 42.394 42.934 2.560

Cl(l/min) 1.870 2.332 1.862 2.416 2.263 1.862 2.101 0.263

MRT(min) 15.664 16.637 18.171 16.220 15.347 18.171 16.702 1.222

VDss(l) 26.135 27.304 28.235 21.425 24.405 28.235 25.956 2.652

(23)

Table 32 生體可用率實驗中六隻家兔口服投與 100 mg/kg 之 Ferulic acid 標準品後血中濃度值(µg/ml)經 WINNOLIN 程式處理之相關藥動學參數

A(µg/ml) 326.58 164.82 163.77 139.83 76.02 395.97 211.17 122.65

B(µg/ml) 3.290 3.718 7.183 5.793 3.979 4.472 4.74 1.47

α^(min^-1⁾ 0.046 0.050 0.051 0.048 0.048 0.047 0.05 0.00

β^(min^-1⁾ 0.041 0.040 0.039 0.038 0.032 0.042 0.04 0.00

AUC(µg.min/ml) 0.011 0.010 0.012 0.012 0.010 0.012 0.01 0.00

K10-HL(min) 0.035 0.032 0.030 0.029 0.026 0.036 0.03 0.00

α-HL(min) 0.004 0.006 0.005 0.005 0.004 0.004 0.00 0.00

β-HL(min) 0.013 0.013 0.015 0.015 0.013 0.014 0.01 0.00

K10(min) 1141.4 1076.9 1426.1 1129.8 1080.6 1406.8 1210.28 161.88

K12(min) 19.882 21.698 22.936 23.896 26.417 19.511 22.39 2.60

K21(min) 14.920 14.000 13.637 14.585 14.356 14.600 14.35 0.46

Volume(l) 16.842 17.301 17.699 18.299 21.490 16.547 18.03 1.81

Cmax(µg./ml) 64.647 68.449 58.645 60.106 66.301 60.262 63.07 3.95

Cl(l/min) 6.031 6.686 5.337 6.713 7.406 4.802 6.16 0.97

MRT(min) 23.730 23.558 23.877 25.216 26.494 23.296 24.36 1.24

VDss(l) 15.994 14.566 18.911 14.202 13.101 20.151 16.15 2.80

(24)

Table 33 六隻家兔靜脈注射不同劑量( 2 . 10 . 50 mg/kg )之 Ferulic acid 標準品後血中濃度值(µg/ml)經 LAGRAN-P 程式處理之相關動力學參數以 One Way ANOVA 比較之結果

Parameter 2 mg/kg 10 mg/kg 50 mg/kg F-value α

=0.05 Result AUC_TOTAL 63.88 ±^5.06 ^333.29±44.53 1569.6 ±^146.1 496.54 3.68 P<0.05

CL 0.031 ±^0.002 ^0.031±^0.004 ^0.032±^0.003 0.315 3.68 N.S.

t_1/2 31.82 ±^0.85 ^35.37±^0.72 ^40.24±^1.23 116.032 3.68 P<0.05 VD_SS 0.90 ±^0.07 ^0.78±^0.12 ^0.85±^0.07 2.607 3.68 N.S.

MRT 28.92 ±^0.80 ^25.42±^0.83 ^26.47±^1.20 21.060 3.68 P<0.05

※ Data are expressed as Mean ±S.D.

N.S.:Non Significant difference

(25)

Table 34 家兔經二次靜脈注射 50 mg/kg 之 Ferulic acid 標準品後血中濃度值(µg/ml)經 WINNONLIN程式處理之相關動力學參數以 t-test 比較之結果

Parameter I.V. ( I ) I.V. ( II ) t-value t_0.975 Result

AUC_TOTAL 1820.8±153.3 200.4±288.3 _1.347 _2.228 _N.S.

t1/2 37.24±1.59 37.25±1.26 _0.08 _2.228 _N.S.

CL 0.062±0.003 0.056±0.006 _2.203 _2.228 _N.S.

VD_SS 1.47±0.05 1.42±0.08 _1.321 _2.228 _N.S.

※ N.S.:Non Significant difference

(26)

Table 35 六隻家兔靜脈注射、肌肉注射及口服投與 Ferulic acid 標準品後血中濃度值(µg/ml)經 LAGRAN-P 程式處理之相關動力學參數以 One Way ANOVA 比較之結果

Parameter I.V. I.M. P.O. F-value α

=0.05 Result AUCPART 1567.5 ±^261.2 ^1335.2±184.1 1131.6 ±^149.2 6.271 3.68 P<0.05 AUC_TOTAL1570.9 ±^261.3 ^1338.6±183.9 1136.1 ±^149.1 6.852 3.68 P<0.05 CL 0.033 ±^0.005 ^0.038±^0.005 ^0.089±^0.011 100.65 3.68 P<0.05 t_1/2 38.845 ±^2.379 ^43.240±1.203 57.914 ±^4.632 19.36 3.68 P<0.05 VD_SS 1.036 ±^0.139 ^1.798±^0.255 ^5.820±^0.884 137.52 3.68 P<0.05 MRT 31.956 ±^1.582 ^47.387±1.629 65.076 ±^3.217 318.84 3.68 P<0.05

※ N.S.:Non Significant difference

Table 36 生體可用率實驗中六隻家兔肌肉注射及口服投藥後之生體可用率

F No. 1 No. 2 No. 3 No. 4 No. 5 No. 6 Mean S.D. C.V.

(%) I.M. ^0.61 ^0.65 ^0.63 ^0.56 ^0.54 ^0.70 ^0.61 ^0.06 ¹⁰

PO ^0.26 ^0.28 ^0.29 ^0.32 ^0.28 ^0.31 ^0.29 ^0.02 ⁷

※ 生體可用率公式請參閱附錄一