TABLE 3.
PBPK model predictions and clinically‐reported pharmacokinetic parameters of midazolam and tacrolimus in the presence and absence of S. sphenanthera extract in healthy people
| C max (ng mL−1) a | AUC0–24h (ng h−1 mL −1) | CL/F (L h−1) | |||||||
|---|---|---|---|---|---|---|---|---|---|
| Victim drug alone | Along with S. sphenantera | Ratio | Victim drug alone | Along with S. sphenantera | Ratio | Victim drug alone | Along with S. sphenantera | Ratio> | |
| Interaction with a single dose of midazolam (15 mg) based on the study by Xin et al. 16 , b | |||||||||
| PBPK prediction | 138.2 | 217.1 | 1.57 | 551.2 | 1,117.5 | 2.03 | 27.2 | 13.4 | 0.49 |
| Clinically‐reported values | 171.4 ± 69.8 | 282.3 ± 152.2 | 1.65 | 577.7 ± 226.8 | 1,185.6 ± 319.8 | 2.05 | 30.9 ± 16.7 | 13.8 ± 5.8 | 0.45 |
| Prediction fold‐difference c | 0.81 | 0.77 | 0.95 | 0.95 | 0.94 | 0.99 | 0.88 | 0.97 | 1.09 |
| Interaction with a single dose of tacrolimus (2 mg) based on the study by Xin et al. 18 , d | |||||||||
| PBPK prediction | 21.5 | 60.5 | 2.81 | 125.2 | 305.1 | 2.44 | 16.0 | 6.6 | 0.41 |
| Clinically‐reported values | 22.2 ± 10.6 | 66.4 ± 12.3 | 2.99 | 129.5 ± 65.1 | 274.8 ± 64.9 | 2.12 | 17.7 ± 12.6 | 6.5 ± 1.5 | 0.37 |
| Prediction fold‐difference | 0.97 | 0.91 | 0.94 | 0.97 | 1.11 | 1.15 | 0.90 | 1.02 | 1.11 |
AUC0–24h, area under the plasma concentration‐time curve during 24 h after dose; CL/F, apparent clearance; C max, peak concentration.
C max was reported as peak plasma and blood concentrations for midazolam and tacrolimus, respectively.
A cross‐over study in healthy Chinese males (n = 12) with age ranged from 21 to 23 years. A single oral dose of midazolam (15 mg) was given with and without S. sphenanthera extract containing schisandrin A (7.25 mg), schisantherin A (7.33 mg) and schisandrol B (0.12 mg) twice daily for 7 days prior to midazolam administration.
Prediction‐fold differences were expressed as the ratio of PBPK prediction to clinically‐observed values.
A cross‐over study in healthy Chinese males (n = 12) with age ranged from 22 to 25 years. A single oral dose of tacrolimus (2 mg) was given in the presence and absence of S. sphenanthera extract containing schisandrin A (7.25 mg), schisantherin A (7.33 mg) and schisandrol B (0.12 mg) twice daily for 13 days prior to tacrolimus administration.