TABLE 4

Comparative tissue distribution of tanshinol after an i.v. bolus dose of tanshinol at 2 mg/kg in rats not treated with probenecid and in rats treated with probenecid

The rat blood and tissue samples were collected at 0, 5, and 30 minutes and 1 and 2 hours after dosing. The details of the rat PK study are described in Materials and Methods (the second rat PK study). AUC_0–∞, area under the plasma concentration-time curve from zero to infinity; C_5min, concentration at 5 min after dosing; MRT, mean residence time; t_1/2, elimination half-life; No obvious effect of tanshinol was observed on the plasma pharmacokinetics or renal disposition of probenecid. The data represent the mean ± S.D. from two independent experiments where each treatment was performed in triplicate (total n = 6).

PK parameter	Rat Treatment with Probenecid
PK parameter	Not Treated	Treated
Heart data
C_5min (μM)	4.18 ± 1.06	7.38 ± 1.49^{^a}
AUC_0–∞ (μM⋅h)	1.16 ± 0.10	3.64 ± 0.50^{^a}
t_1/2 (h)	0.235 ± 0.027	0.429 ± 0.138^{^a}
MRT (h)	0.353 ± 0.05	0.588 ± 0.115^{^a}
Lung data
C_5min (μM)	2.80 ± 0.29	4.25 ± 0.54^{^a}
AUC_0–∞ (μM⋅h)	0.72 ± 0.09	2.05 ± 0.12^{^a}
t_1/2 (h)	0.15 ± 0.00	0.32 ± 0.02^{^a}
MRT (h)	0.26 ± 0.01	0.50 ± 0.03^{^a}
Brain data
C_5min (μM)	0.212 ± 0.101	0.309 ± 0.068^{^a}
AUC_0–∞ (μM⋅h)	0.0729 ± 0.0177	0.173 ± 0.055^{^a}
t_1/2 (h)	0.223 ± 0.116	0.363 ± 0.077^{^a}
MRT (h)	0.343 ± 0.19	0.543 ± 0.091^{^a}
Liver data
C_5min (μM)	0.601 ± 0.298	1.35 ± 0.32^{^a}
AUC_0–∞ (μM⋅h)	0.227 ± 0.143	0.644 ± 0.206^{^a}
t_1/2 (h)	0.124 ± 0.025	0.293 ± 0.018^{^a}
MRT (h)	0.201 ± 0.065	0.442 ± 0.037^{^a}
Kidney data
C_5min (μM)	127 ± 18	68.0 ± 16.7^{^a}
AUC_0–∞ (μM⋅h)	23.6 ± 3.2	26.5 ± 5.7
t_1/2 (h)	0.225 ± 0.032	0.286 ± 0.032^{^a}
MRT (h)	0.216 ± 0.012	0.378 ± 0.031^{^a}
Plasma data
C_5min (μM)	13.3 ± 2.5	28.3 ± 5.1^{^a}
AUC_0–∞ (μM⋅h)	4.17 ± 0.62	12.6 ± 1.5^{^a}
t_1/2 (h)	0.287 ± 0.057	0.396 ± 0.095^{^a}
MRT (h)	0.238 ± 0.020	0.416 ± 0.034^{^a}

↵^a P < 0.05 when compared with the rat group not treated with probenecid.