Table 3.
Comparative IC50 values for ginsenosides on human OATP1B3 and OATP1B1 activities (mediating transport of E217βG) and associated DDI indices
| Compound | IC50 | Unbound Cmax | t1/2 | R | DDI index |
|---|---|---|---|---|---|
| (μM) | (μM) | (h) | |||
| OATP1B3 | |||||
| Rifampin | 1.63 ± 0.25 | 1.84–3.45 | 1.00–4.40 | 1.00–1.02 | 1.13–2.16 |
| Ginsenoside Rg1 | 43.1 ± 3.0 | 0.789–5.00 | 1.27–2.01 | 1.00 | 0.0183–0.116 |
| Ginsenoside Re | 39.4 ± 3.5 | 0.210–0.226 | 0.59–0.88 | 1.00 | 0.00533–0.00574 |
| Notoginsenoside R1 | 332 ± 29 | 0.812 | 1.41 | 1.00 | 0.00245 |
| Ginsenoside Rb1 | 0.467 ± 0.051 | 0.085–0.242 | 40.1–48.0 | 2.95–3.41 | 0.540–1.77 |
| Ginsenoside Rc | 0.208 ± 0.030 | — | — | — | — |
| Ginsenoside Rd | 0.235 ± 0.022 | 0.005 | 36.6 | 2.74 | 0.0583 |
| OATP1B1 | |||||
| Rifampin | 3.79 ± 0.28 | 1.84–3.45 | 1.00–4.40 | 1.00–1.02 | 0.485–0.928 |
| Ginsenoside Rg1 | 70.4 ± 9.9 | 0.789–5.00 | 1.27–2.01 | 1.00 | 0.0112–0.0710 |
| Ginsenoside Re | 133 ± 15 | 0.210–0.226 | 0.59–0.88 | 1.00 | 0.00158–0.00170 |
| Notoginsenoside R1 | 359 ± 101 | 0.812 | 1.41 | 1.00 | 0.00226 |
| Ginsenoside Rb1 | 4.60 ± 0.75 | 0.085–0.242 | 40.1–48.0 | 2.95–3.41 | 0.0545–0.179 |
| Ginsenoside Rc | 2.72 ± 0.26 | — | — | — | — |
| Ginsenoside Rd | 1.42 ± 0.12 | 0.005 | 36.6 | 2.74 | 0.00965 |
The clinical Cmax and t1/2 values of rifampin at the therapeutic dose of 600 mg per day (p.o. administration) were from reported human data (Acocella, 1978; Loos et al., 1985). The clinical Cmax and t1/2 values of ginsenosides were from our PK data of human subjects receiving XueShuanTong (a ginsenoside injection prepared from Sanqi; details pending publication elsewhere) and from the reported human PK data for ShenMai injection and ShengMai injection by Li et al. (2011). The drug–drug interaction index (DDI index = unbound Cmax·R/IC50) were calculated for the transporter-ginsenoside couples. R is the accumulative factor that is calculated using the equation R = 1/(1 − e−kτ), where k is the elimination rate constant (0.693/t1/2) and τ is the dosing interval (24 h). A DDI index value greater than 0.1 indicates the potential for DDIs and the need for an in vivo DDI study. Values represent the means ± SDs (n = 6, except for the values for rifampin for which n = 3).