Comparative plasma pharmacokinetics and renal excretion of tanshinol after an i.v. bolus dose of tanshinol at 2 mg/kg in rats not treated with probenecid and in the same rats treated with probenecid
The details of the rat PK study are described in Materials and Methods (the first rat PK study). No obvious effect of tanshinol was observed on the plasma pharmacokinetics or renal disposition of probenecid. The data represent mean ± S.D. from two independent experiments where each treatment was performed in tetraplicate (total n = 8).
| PK Parameter | Rat Treatment with Probenecid | |
|---|---|---|
| Not treated | Treated (Same Rats) | |
| Plasma data | ||
| C5min (μM) | 11.8 ± 1.9 | 23.2 ± 3.6a |
| AUC0–∞ (μM⋅h) | 3.19 ± 0.57 | 10.6 ± 3.1a |
| t1/2 (h) | 0.196 ± 0.055 | 0.441 ± 0.062a |
| MRT (h) | 0.173 ± 0.015 | 0.450 ± 0.052a |
| CLtot, p (l/h/kg) | 3.26 ± 0.64 | 1.01 ± 0.24a |
| VSS (l/kg) | 0.538 ± 0.087 | 0.428 ± 0.077a |
| Urine data | ||
| Cum.Ae (μmol) | 1.51 ± 0.09 | 1.28 ± 0.14a |
| CLR (l/h/kg) | 1.94 ± 0.38 | 0.503 ± 0.096a |
| fe-U (%) | 59.7 ± 3.8 | 50.7 ± 5.7a |
| CLR/(GFR×fu) | 6.56 | 1.72 |
| Plasma protein binding data | ||
| fu (%; at 0.5–50 μM) | 98.6 ± 1.1 | 96.5 ± 2.5 |
| GFR data | ||
| CLR-cr (l/h/kg) (Before dosing) | 0.295 ± 0.043 | 0.315 ± 0.036 |
| CLR-cr (l/h/kg) (6 h after dosing) | 0.314 ± 0.060 | 0.288 ± 0.037 |
Cum.Ae, cumulative amount excreted; MRT, mean residence time.
↵a P < 0.05 when compared with the rat group not treated with probenecid.