Table 1.
Pharmacokinetics of ginsenosides Rb1 (1), Rd (2), and Rg1 (31) and notoginsenoside R1 (32) in human subjects who received intravenous XueShuanTong
| Compound (ID) | Cmax (µmol/L) | AUC0-t (μmol/L·h) | AUC0-∞ (μmol/L·h) | t1/2 (h) | CLtot, p (mL/h/kg) | Vss (mL/kg) | fu (%) | fe-U (%) |
|---|---|---|---|---|---|---|---|---|
| Human study 1 (dose, 250 mg XueShuanTong per person): subject ID, m1‒m8 (male); body weight, 53.0‒88.8 kg; age, 21‒32 years old) | ||||||||
| Ginsenoside Rb1 (1) | 16.3 ± 3.7 | 425.5 ± 68.0 | 622.9 ± 101.1 | 43.5 ± 6.5 | 1.4 ± 0.2 | 80.6 ± 8.7 | 2.5 ± 0.7 | 38.4 ± 7.0 |
| Ginsenoside Rd (2) | 0.7 ± 0.2 | 13.8 ± 2.3 | 49.7 ± 25.0 | 175.9 ± 83.0 | 1.8 ± 0.6 | 142.4 ± 25.0 | 2.1 ± 0.8 | 20.1 ± 2.6 |
| Ginsenoside Rg1 (31) | 3.6 ± 0.5 | 7.8 ± 0.9 | 7.9 ± 0.9 | 1.3 ± 0.2 | 278.9 ± 41.6 | 338.8 ± 35.5 | 98.3 ± 3.7 | 42.1 ± 4.5 |
| Notoginsenoside R1 (32) | 0.7 ± 0.1 | 1.6 ± 0.2 | 1.6 ± 0.2 | 1.4 ± 0.2 | 204.5 ± 28.8 | 283.2 ± 30.2 | 90.0 ± 10.6 | 49.4 ± 6.8 |
| Human study 1 (dose, 250 mg XueShuanTong per person): subject ID, f1‒f6 (female); body weight, 50.1‒59.3 kg; age, 24‒27 years old) | ||||||||
| Ginsenoside Rb1 (1) | 19.5 ± 2.2 | 492.4 ± 46.7 | 691.1 ± 65.9 | 39.9 ± 4.7 | 1.5 ± 0.1 | 82.4 ± 13.3 | 1.1 ± 0.3 | 42.7 ± 13.2 |
| Ginsenoside Rd (2) | 0.8 ± 0.1 | 14.2 ± 2.5 | 36.1 ± 15.6 | 133.9 ± 112.4 | 2.5 ± 0.5 | 143.0 ± 24.0 | 1.0 ± 0.5 | 18.6 ± 4.2 |
| Ginsenoside Rg1 (31) | 5.0 ± 0.6 | 12.8 ± 3.1 | 12.8 ± 3.2 | 1.3 ± 0.3 | 219.4 ± 64.4 | 272.3 ± 43.0 | 83.5 ± 8.2 | 45.1 ± 13.4 |
| Notoginsenoside R1 (32) | 1.0 ± 0.1 | 2.4 ± 0.6 | 2.5 ± 0.6 | 1.3 ± 0.3 | 174.5 ± 47.3 | 253.0 ± 37.4 | 78.5 ± 17.8 | 48.5 ± 13.2 |
| Human study 1 (dose, 500 mg XueShuanTong per person): subject ID, m9‒m16 (male); body weight, 57.0‒78.0 kg; age, 25‒32 years old) | ||||||||
| Ginsenoside Rb1 (1) | 26.3 ± 2.6 | 737.7 ± 99.3 | 1069.4 ± 179.9 | 42.9 ± 7.5 | 1.6 ± 0.2 | 92.8 ± 10.9 | 1.2 ± 0.2 | 41.9 ± 4.3 |
| Ginsenoside Rd (2) | 1.3 ± 0.2 | 25.2 ± 3.8 | 66.1 ± 26.7 | 125.9 ± 75.9 | 2.2 ± 0.4 | 143.4 ± 18.1 | 0.5 ± 0.1 | 18.6 ± 1.5 |
| Ginsenoside Rg1 (31) | 6.4 ± 0.6 | 16.9 ± 2.0 | 16.9 ± 2.1 | 1.2 ± 0.1 | 267.2 ± 51.6 | 308.4 ± 37.5 | 78.1 ± 8.8 | 36.1 ± 4.6 |
| Notoginsenoside R1 (32) | 1.2 ± 0.1 | 3.3 ± 0.4 | 3.3 ± 0.4 | 1.3 ± 0.1 | 205.1 ± 38.5 | 277.5 ± 32.0 | 85.7 ± 6.7 | 50.8 ± 5.3 |
| Human study 1 (dose, 500 mg XueShuanTong per person): subject ID, f7‒f12 (female); body weight, 48.7‒66.8 kg; age, 21‒27 years old) | ||||||||
| Ginsenoside Rb1 (1) | 28.9 ± 3.2 | 887.4 ± 97.5 | 1269.9 ± 206.6 | 41.0 ± 7.6 | 1.5 ± 0.3 | 87.5 ± 9.7 | 1.9 ± 0.2 | 44.5 ± 17.5 |
| Ginsenoside Rd (2) | 1.2 ± 0.1 | 26.4 ± 2.2 | 68.6 ± 29.9 | 119.7 ± 82.0 | 2.2 ± 0.3 | 161.2 ± 19.2 | 1.5 ± 0.7 | 17.5 ± 6.5 |
| Ginsenoside Rg1 (31) | 7.7 ± 0.8 | 20.7 ± 2.7 | 20.8 ± 2.8 | 1.3 ± 0.1 | 240.1 ± 33.5 | 354.9 ± 26.8 | 97.5 ± 3.0 | 53.8 ± 17.5 |
| Notoginsenoside R1 (32) | 1.5 ± 0.2 | 4.1 ± 0.5 | 4.1 ± 0.5 | 1.5 ± 0.1 | 184.8 ± 24.9 | 311.6 ± 25.8 | 94.5 ± 6.7 | 62.0 ± 18.1 |
| Human study 2 (dose, 500 mg XueShuanTong once daily; day 4): subject ID, m17‒m24 (male); body weight, 57.4‒73.8 kg; age, 25‒33 years old) | ||||||||
| Ginsenoside Rb1 (1) | 23.0 ± 5.8 | 245.1 ± 25.1 | 745.0 ± 236.6 | – | 2.1 ± 0.8 | 143.3 ± 20.3 | – | – |
| Ginsenoside Rd (2) | 1.3 ± 0.3 | 11.0 ± 1.4 | 20.5 ± 5.8 | – | 4.5 ± 1.5 | 122.3 ± 15.2 | – | – |
| Ginsenoside Rg1 (31) | 6.9 ± 1.1 | 16.9 ± 1.6 | 17.0 ± 1.6 | 1.4 ± 0.2 | 268.5 ± 33.0 | 342.0 ± 53.8 | – | – |
| Notoginsenoside R1 (32) | 1.3 ± 0.2 | 3.4 ± 0.3 | 3.4 ± 0.3 | 1.4 ± 0.1 | 205.0 ± 28.9 | 296.0 ± 42.5 | – | – |
| Human study 2 (dose, 500 mg XueShuanTong once daily; day 18): subject ID, m17‒m24 (male); body weight, 57.4‒73.8 kg; age, 25‒33 years old) | ||||||||
| Ginsenoside Rb1 (1) | 68.8 ± 11.3 | 2632.0 ± 521.1 | 4376.3 ± 1200.6 | 52.7 ± 6.9 | 0.4 ± 0.1 | 31.0 ± 4.8 | – | 128.4 ± 28.6 |
| Ginsenoside Rd (2) | 4.1 ± 1.0 | 146.1 ± 53.6 | 303.6 ± 154.0 | 74.6 ± 25.9 | 0.4 ± 0.2 | 31.0 ± 10.5 | – | 127.1 ± 39.8 |
| Ginsenoside Rg1 (31) | 8.0 ± 1.3 | 25.5 ± 3.2 | 25.5 ± 3.2 | 2.5 ± 0.1 | 180.5 ± 29.4 | 301.7 ± 41.9 | – | 61.0 ± 17.0 |
| Notoginsenoside R1 (32) | 1.6 ± 0.3 | 4.7 ± 0.5 | 4.8 ± 0.5 | 1.7 ± 0.2 | 145.2 ± 19.7 | 255.0 ± 28.0 | – | 25.6 ± 6.2 |
The details of human pharmacokinetic study are described in “Materials and methods” section (Human studies). The data represent mean ± standard deviation
Cmax maximum plasma concentration, AUC0-t area under the plasma concentration–time curve from 0 to last measured time point, AUC0-∞, area under the plasma concentration–time curve from 0 to infinity, t1/2, terminal half-life, CLtot,p total plasma clearance, VSS apparent volume of distribution at steady state, fu unbound fraction in plasma, fe-U fraction of dose excreted into urine