Table 3.
Pharmacokinetic parameters of detected compounds following oral/intravenous/intraperitoneal administration of bioactive compounds from AR.
| Administration | Species | Dose | Detected compounds | Pharmacokinetic parameters | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Cmax (ng/mL) | Tmax (h) | AUC(0-t) (h·ng/mL) | AUC(0-∞) (h·ng/mL) | MRT (min) | T1/2 (h) | CL (L·h-1·kg-1) | Vd (L/kg) | Vss (L/kg) | ||||
| Formononetin, p.o. [217] | Rat | 50 mg/kg | Formononetin | 16.67 ± 6.60 | 1.00 ± 0.00 | 251.44 ± 63.67 | 278.27 ± 66.68 | ND | ND | ND | ND | NA |
| Daidzin | 8.99 ± 3.29 | ND | 145.58 ± 34.70 | ND | ND | ND | ND | ND | NA | |||
| Daidzin + Daidzin conjugates | 301.33 ± 149.92 | ND | 5032.25 ± 530.22 | ND | ND | ND | ND | ND | NA | |||
| Formononetin conjugates | 311.97 ± 97.36 | ND | 5231.46 ± 1219.91 | ND | ND | ND | ND | ND | NA | |||
| Daidzin conjugates | 292.70 ± 146.20 | ND | 4886.67 ± 1498.49 | ND | ND | ND | ND | ND | NA | |||
| Formononetin + Formononetin conjugates | 327.67 ± 100.72 | 3.42 ± 2.74 | 5482.90 ± 1276.11 | 6509.66 ± 720.47 | ND | ND | ND | ND | NA | |||
| Formononetin, i.v. [217] | Rat | 10 mg/kg | Formononetin | 4548.50 ± 321.73 | NA | 1949.10 ± 295.09 | 1975.88 ± 317.15 | ND | 1.95 ± 0.48 | 5.13 ± 0.82 | 14.16 ± 1.26 | NA |
| Daidzin | 434 ± 19.80 | NA | 279.72 ± 52.03 | ND | ND | ND | ND | ND | NA | |||
| Daidzin + Daidzin conjugates | 494 ± 5.66 | NA | 1663.89 ± 5.72 | ND | ND | ND | ND | ND | NA | |||
| Formononetin conjugates | 962.00 ± 311.13 | NA | 3003.64 ± 321.79 | ND | ND | ND | ND | ND | NA | |||
| Daidzin conjugates | 308.20 ± 95.32 | NA | 1356.60 ± 42.89 | ND | ND | ND | ND | ND | NA | |||
| Formononetin + Formononetin conjugates | 5180 ± 367.70 | NA | 4976.60 ± 648.18 | 5098.57 ± 765.53 | ND | 5.09 ± 1.61 | ND | 14.23 ± 2.41 | NA | |||
| Formononetin, i.v. [216] | Rat | 10 mg/kg | Formononetin | 3207 | NA | 1683.86 | 1773.40 | ND | 10.34 | 5.63 | 84.14 | NA |
| Formononetin + Formononetin conjugates | 3676 | NA | 4317.62 | 4595.71 | ND | 7.18 | 2.17 | 22.54 | NA | |||
| Daidzin | 305.73 | NA | 243.68 | 263.86 | ND | 2.53 | ND | ND | NA | |||
| Daidzin + Daidzin conjugates | 347.73 | NA | 1625.02 | 1773.89 | ND | 6.85 | ND | ND | NA | |||
| Formononetin, p.o. [218] | Rat | 20 mg/kg | Formononetin | 81.04 ± 9.63 | 0.5 ± 0.0 | 191.38 ± 12.39 | 203.26 ± 12.93 | ND | 2.10 ± 0.28 | ND | NA | NA |
| Formononetin, i.v. [218] | Rat | 4 mg/kg | Formononetin | 349.48 ± 34.63 | NA | 174.99 ± 23.90 | 184.97 ± 24.71 | ND | 2.23 ± 0.6 | 4.3 ± 0.8 | 13.9 ± 1.0 | ND |
| CG, i.v. [223] | Rat | 0.5 mg/kg | CG | 446.1 ± 84.6 | NA | 89.33 ± 17.00 | 89.83 ± 17.00 | ND | 0.38 ± 0.14 | ND | ND | ND |
| CG glucuronide | 5.41 ± 1.22 | 0.57 ± 0.30 | 10.00 ± 5.17 | 12.83 ± 5.33 | ND | 0.95 ± 0.33 | ND | ND | ND | |||
| C-3′-G | 10.11 ± 3.17 | 0.32 ± 0.09 | 34.00 ± 23.83 | 54.83 ± 50.55 | ND | 4.11 ± 3.41 | ND | ND | ND | |||
| CG, p.o. [223] | Rat | 10 mg/kg | CG | 7.46 ± 3.76 | 0.28 ± 0.11 | 5.33 ± 1.83 | 5.50 ± 2.67 | ND | 1.52 ± 0.46 | ND | ND | NA |
| CG glucuronide | 51.29 ± 15.7 | 1.00 ± 0.39 | 106.33 ± 55.17 | 106.67 ± 55.50 | ND | 1.03 ± 0.24 | ND | ND | NA | |||
| C-3′-G | 1189.66 ± 346.95 | 0.96 ± 0.43 | 1574.50 ± 346.00 | 1852.67 ± 569.67 | ND | 2.86 ± 1.21 | ND | ND | NA | |||
| CG, i.p. [223] | Rat | 10 mg/kg | CG | 965.24 ± 133.53 | 0.25 ± 0.06 | 1199.67 ± 373.83 | 1210.67 ± 368.00 | ND | 1.29 ± 0.30 | ND | ND | NA |
| CG glucuronide | 322.24 ± 125.53 | 1.10 ± 0.42 | 1681.33 ± 642.67 | 2422.50 ± 1118.33 | ND | 6.65 ± 4.85 | ND | ND | NA | |||
| C-3′-G | 221.62 ± 86.60 | 1.10 ± 0.42 | 1151.83 ± 443.33 | 1651.83 ± 765.00 | ND | 6.57 ± 4.82 | ND | ND | NA | |||
| CG, p.o. [224] | Rat | 120 mg/kg | CG | 1870.00 ± 360.00 | 0.67 ± 0.08 | 1595.33 ± 472.33 | 1679.67 ± 509.00 | ND | 0.19 ± 0.02 (Ka); 0.26 ± 0.02 (Ke) | 71.40 ± 16.20 | ND | NA |
| Ononin, p.o. [218] | Rat | 20 mg/kg | Ononin | (1) 2.11 ± 11.23 (2) 4.63 ± 3.62 |
(1) 0.5 ± 0.0 (2) 4.0 ± 0.0 |
68.95 ± 16.83 | 74.59 ± 18.55 | ND | 1.82 ± 0.56 | ND | ND | NA |
| Formononetin | (1) 44 ± 2.71 (2) 0.52 ± 3.35 |
(1) 1.0 ± 0.0 (2) 5.7 ± 0.0 |
85.09 ± 13.17 | ND | ND | NA | ND | ND | NA | |||
| Ononin, i.v. [218] | Rat | 4 mg/kg | Ononin | 491.61 ± 44.42 | NA | 189.17 ± 23.29 | 199.62 ± 25.87 | ND | 1.92 ± 0.8 | 6.6 ± 0.9 | 18.4 ± 1.5 | ND |
| AS-IV, p.o. [225] | Rat | 20 mg/kg | AS-IV | 92.4 ± 14.2 | 1.0 ± 0.5 | 419.50 ± 126.65 | 420.41 ± 129.01 | ND | t1/2α = 0.89 ± 0.37; t1/2β = 22.02 ± 8.26 | 0.045 ± 0.013 | 0.19 ± 0.15 | NA |
| AS-IV, i.v. [226] | Rat (male) | 0.75 mg/kg | AS-IV | 3790 | NA | ND | 4816.67 | 122 | 1.64 | 0.3 | 0.39 | 0.63 |
| AS-IV, i.v. [226] | Rat (female) | 0.75 mg/kg | AS-IV | 5180 | NA | ND | 2550 | 47.4 | 0.57 | 0.3 | 0.14 | 0.23 |
| AS-IV, i.v. [226] | Rat (male) | 1.5 mg/kg | AS-IV | 6980 | NA | ND | 6700 | 95.2 | 1.12 | 0.42 | 0.43 | 0.71 |
| AS-IV, i.v. [226] | Rat (female) | 1.5 mg/kg | AS-IV | 4800 | NA | ND | 4966.67 | 90.1 | 1.12 | 0.18 | 0.16 | 0.23 |
| AS-IV, i.v. [226] | Rat (male) | 3 mg/kg | AS-IV | 7790 | NA | ND | 8666.67 | 98.7 | 1.20 | 0.36 | 0.38 | 0.57 |
| AS-IV, i.v. [226] | Rat (female) | 3 mg/kg | AS-IV | 7240 | NA | ND | 9183.33 | 149 | 2.48 | 0.18 | 0.21 | 0.41 |
| AS-IV, i.v. [226] | Dog (male) | 0.25 mg/kg | AS-IV | 1110 ± 280 | NA | ND | 1218.33 ± 516.67 | 71.5 ± 7.0 | 0.87 ± 0.14 | 0.24 ± 0.06 | 0.23 ± 0.05 | 0.32 ± 0.13 |
| AS-IV, i.v. [226] | Dog (female) | 0.25 mg/kg | AS-IV | 1130 ± 40 | NA | ND | 1096.67 ± 300.00 | 82.8 ± 29 | 1.05 ± 0.37 | 0.24 ± 0.06 | 0.22 ± 0.01 | 0.36 ± 0.04 |
| AS-IV, i.v. [226] | Dog (male) | 0.5 mg/kg | AS-IV | 4390 ± 2600 | NA | ND | 2600.00 ± 121.67 | 75.5 ± 6.9 | 1.00 ± 0.14 | 0.24 ± 0.06 | 0.14 ± 0.07 | 0.32 ± 0.09 |
| AS-IV, i.v. [226] | Dog (female) | 0.5 mg/kg | AS-IV | 3480 ± 1600 | NA | ND | 2883.33 ± 766.67 | 78.0 ± 8.5 | 1.12 ± 0.13 | 0.24 ± 0.06 | 0.16 ± 0.07 | 0.31 ± 0.06 |
| AS-IV, i.v. [226] | Dog (male) | 1 mg/kg | AS-IV | 7920 ± 3700 | NA | ND | 6033.33 ± 1316.67 | 83.0 ± 23 | 1.15 ± 0.35 | 0.24 ± 0.06 | 0.14 ± 0.07 | 0.28 ± 0.08 |
| AS-IV, i.v. [226] | Dog (female) | 1 mg/kg | AS-IV | 8860 ± 2500 | NA | ND | 5916.67 ± 1366.67 | 64.8 ± 16 | 0.84 ± 0.22 | 0.18 ± 0.06 | 0.12 ± 0.04 | 0.23 ± 0.04 |
| AS-IV, i.v. [227] | Rat | 2.5 mg/kg | AS-IV | ND | NA | ND | 5990 | ND | 3.37 | 0.42 | 0.77 | ND |
| AS-IV, p.o. [228] | Rat | 20 mg/kg | AS-IV | 374 | 0.43 | ND | 1062 | ND | t1/2α = 0.30; t1/2β = 4.65; | 0.43 | 0.56 | NA |
| AS-IV, p.o. [229] | Rat | 10 mg/kg | AS-IV | 27.08 ± 16.17 | 2.00 ± 63 | 85.56 ± 43.17 | ND | ND | 1.71 ± 1.16 | ND | ND | NA |
| Cycloastragenol | 3.48 ± 2.34 | 9.67 ± 0.82 | 13.15 ± 8,78 | ND | ND | ND | ND | ND | NA | |||
| Iso-cycloastragenol | 7.02 ± 3.68 | 8.00 ± 0.00 | 38.23 ± 17.22 | ND | ND | 4.77 ± 3.26 | ND | ND | NA | |||
| AS-IV, i.v. [229] | Rat | 1.5 mg/kg | AS-IV | 7865.40 ± 570.67 | NA | 7917.21 ± 1038.52 | ND | ND | 1.29 ± 0.41 | ND | ND | ND |
| Cycloastragenol | 1.21 ± 0.22 | 8.33 ± 0.82 | 2.73 ± 0.79 | ND | ND | ND | ND | ND | ND | |||
| Iso-cycloastragenol | 2.98 ± 0.86 | 8.00 ± 0.00 | 15.80 ± 2.60 | ND | ND | 3.05 ± 1.06 | ND | ND | ND | |||
| AS-IV, i.v. [230] | Dog | 0.5 mg/kg | AS-IV | ND | NA | 1998.22 | 2104 | 222.61 | 2.953 | 0.24 | ND | 0.74 |
| AS-IV, i.v. [230] | Dog | 1 mg/kg | AS-IV | ND | NA | 4380 | 4604.67 | 232.48 | 3.28 | 0.24 | ND | 0.61 |
| AS-IV, i.v. [230] | Dog | 2 mg/kg | AS-IV | ND | NA | 11706.67 | 12075.17 | 241.80 | 4.03 | 0.18 | ND | 0.61 |
| AS-IV, p.o. [230] | Dog | 10 mg/kg | AS-IV | ND | NA | 3368.33 | 3400.83 | 261.14 | 3.83 | 0.6 | ND | 2.61 |
p.o., oral administration; i.v., intravenous administration; i.p., intraperitoneal administration; C-3′-G, calycosin-3′-glucuronide; CG, calycosin-7-β-glucoside; CG-3′-G, CG-3′-glucuronide; F-7-G, formononetin-7-glucuronide; D-7-G, daidzein-7-glucuronide; AS-IV, astragaloside IV. NA, not applicable; ND, not determined.