TABLE 5.

Comparative plasma and kidney pharmacokinetics of tanshinol in rats receiving an i.v. bolus dose of tanshinol solution (2–200 mg/kg)

The rat blood and kidney tissue samples were collected at 5 and 30 minutes and 1 and 2 hours after dosing. Urine samples were collected 0–24 hours after dosing. The details of the rat PK study are described in Materials and Methods (the third rat PK study).

PK Parameter	Dosage
PK Parameter	2	5	15	50	200
	mg/kg
Plasma data
C_5min (μM)	15.5 ± 1.5	36.7 ± 2.9	98.7 ± 17.9	388 ± 48	1403 ± 98
AUC_0–∞ (μM⋅h)	4.33 ± 0.45	11.0 ± 1.0	31.2 ± 5.5	125 ± 23	504 ± 61
t_1/2 (h)	0.278 ± 0.017	0.285 ± 0.010	0.260 ± 0.027	0.269 ± 0.022	0.259 ± 0.014
MRT (h)	0.272 ± 0.030	0.252 ± 0.004	0.237 ± 0.031	0.288 ± 0.002	0.328 ± 0.009
V_SS (l/kg)	0.635 ± 0.023	0.582 ± 0.049	0.578 ± 0.052	0.595 ± 0.097	0.662 ± 0.067
CL_{tot, p} (l/h/kg)	2.35 ± 0.25	2.31 ± 0.20	2.48 ± 0.45	2.07 ± 0.34	2.02 ± 0.26
Urine data
Cum.A_e (μmol)	1.48 ± 0.06	3.75 ± 0.29	12.3 ± 1.1	44.2 ± 2.9	192 ± 18
f_e-U (%)	61.5 ± 3.6	59.7 ± 6.8	66.3 ± 7.5	73.3 ± 5.7	77.9 ± 6.7
CL_R (l/h/kg)	1.44 ± 0.10	1.37 ± 0.05	1.62 ± 0.11	1.50 ± 0.15	1.56 ± 0.06
Kidney data
C_5min (μM)	118 ± 37	278 ± 79	1083 ± 410	3199 ± 1046	9671 ± 1536
AUC_0–∞ (μM⋅h)	22.7 ± 6.9	67.9 ± 18.0	268 ± 97	899 ± 309	3552 ± 518
t_1/2 (h)	0.277 ± 0.010	0.250 ± 0.031	0.238 ± 0.003	0.267 ± 0.016	0.256 ± 0.007
MRT (h)	0.232 ± 0.011	0.197 ± 0.028	0.172 ± 0.008	0.214 ± 0.010	0.254 ± 0.011
CL_R,c-u (l/h/kg)	0.289 ± 0.075	0.282 ± 0.064	0.261 ± 0.061	0.269 ± 0.062	0.272 ± 0.017

AUC_0–∞, area under the plasma concentration-time curve from 0 to infinity; CL_R,c-u, renal clearance by the cellular efflux into urine across the apical brush border membrane; CL_R, renal clearance; CL_tot,p, total plasma clearance; C_5min, concentration at 5 min after dosing; Cum.A_e, cumulative amount excreted; MRT, mean residence time; t_1/2, elimination half-life; V_SS, apparent volume of distribution at steady state.