Table 1.

Effects of acute cotreatment with Radix Rehmanniae (RR), Fructus Schisandrae (FS), Radix Bupleuri (RB), and Fructus Gardeniae (FG) on the pharmacokinetics of plasma clozapine, norclozapine (norCLZ), and clozapine N-oxide (CLZ N-oxide) in rats after an intraperitoneal dose of 10 mg/kg clozapine ^a,b.

Variable b	CLZ Alone (n = 5)	RR + CLZ (n = 4)	FS + CLZ (n = 6)	RB + CLZ (n = 6)	FG + CLZ (n = 4)
CLZ
Cmax (nM)	1721 ± 349	1118 ± 350	1434 ± 232	1807 ± 205	1344 ± 469
Tmax (h)	0.20 ± 0.12	0.12 ± 0.042	0.40 ± 0.14	0.28 ± 0.08	0.36 ± 0.14
AUC0-C6 (nM∙h)	2370 ± 526	1418 ± 543	2640 ± 350	2992 ± 509	1871 ± 649
t1/2 (h)	1.16 ± 0.091	1.01 ± 0.7	2.50 ± 1.06	1.17 ± 0.15	2.09 ± 0.99
MRT (h)	1.57 ± 0.053	1.45 ± 0.085	2.46 ± 0.74	1.82 ± 0.30	2.68 ± 1.17
CL/F (L/h/kg)	16.7 ± 4.43	30.1 ± 8.06	12.9 ± 2.01	11.7 ± 1.77	55.2 ± 41.8
Vd (L)	27.1 ± 6.36	43.6 ± 10.9	39.0 ± 12.5	18.3 ± 1.72	94.0 ± 50.3
NorCLZ
Cmax (nM)	3644 ± 426	3283 ± 461	1996 ± 620	2364 ± 879	768 ± 379 (0.008) *
Tmax (h)	0.27 ± 0.07	0.25 ± 0	0.67 ± 0.27	0.64 ± 0.30	1.15 ± 0.95
AUC0-C5 (nM∙h)	5819 ± 382	4238 ± 875	2862 ± 878 (0.013) *	2878 ± 908 (0.014) *	1463 ± 619 (0.002) *
t1/2 (h)	1.08 ± 0.09	1.05 ± 0.10	1.20 ± 0.19	1.08 ± 0.16	1.5 ± 0.38
MRT (h)	1.66 ± 0.10	1.34 ± 0.10	1.75 ± 0.39	1.97 ± 0.47	2.61 ± 0.86
CLZ N-oxide
Cmax (nM)	185 ± 21.3	139± 14.0	112 ± 28.2	134 ± 47.2	58.2 ± 42.8 (0.008) *
Tmax (h)	0.25± 0	0.25 ± 0	0.46 ± 0.12	0.64 ± 0.30	0.21 ± 0.11
AUC0-C1 (nM∙h)	159 ± 16.2	82.5 ± 10.9 (0.023) *	130 ± 14.2	81.6 ± 23.4 (0.012) *	43.1 ± 33.1 (0.007) *
t1/2 (h)	0.69 ± 0.12	0.39 ± 0.09	1.04 ± 0.44	0.39 ± 0.04	0.59 ± 0.12
MRT (h)	0.95 ± 0.15	0.57 ± 0.13	1.43 ± 0.61	0.79 ± 0.15	0.70 ± 0.21

^a. Data are expressed as mean ± SEM and analyzed using one-way ANOVA. * P value compared with the CLZ alone group; ^b. C_max, peak concentration; T_max, time to reach C_max; AUC_0-∞, area under the concentration-time curve from time zero to infinity; t_1/2, elimination half-life; CL/F, total body clearance; MRT, mean residence time; V_d, volume of distribution.