Table 2.

Effects of chronic co-treatment 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 intraperitoneal administration of 10 mg/kg clozapine for 11 days ^a,b.

Variable b	CLZ Alone (n = 5)	RR + CLZ (n = 6)	FS + CLZ (n = 4)	RB + CLZ (n = 4)	FG + CLZ (n = 4)
CLZ
Cmax (nM)	1430 ± 122	1499 ± 280	1537 ± 118	1330 ± 125	2493 ± 472
Tmax (h)	0.15 ± 0.04	0.21 ± 0.07	0.08 ± 0	0.19 ± 0.10	0.12 ± 0.04
AUC0-∞ (nM∙h)	2039 ± 211	2710 ± 545	1886 ± 218	2190 ± 408	2429 ± 138
t1/2 (h)	1.36 ± 0.23	2.40 ± 0.82	1.26 ± 0.47	2.19 ± 1.10	1.25 ± 0.21
MRT (h)	1.63 ± 0.13	2.43 ± 0.59	1.31 ± 0.07	1.75 ± 0.46	1.39 ± 0.21
CL/F (L/h/kg)	15.5 ± 1.30	14.1 ± 3.10	17.0 ± 2.19	15.4 ± 2.57	12.8 ± 0.75
Vd (L)	26.5 ± 50.2	33.0 ± 9.48	30.9 ± 11.9	38.3 ± 11.8	21.5 ± 2.66
NorCLZ
Cmax (nM)	4050 ± 268	4677 ± 807	4383 ± 444	3754 ± 1266	3200 ± 528
Tmax (h)	0.30 ± 0.05	0.29 ± 0.04	0.25 ± 0	0.31 ± 0.06	0.31 ± 0.06
AUC0-∞ (nM∙h)	7192 ± 762	11494 ± 2767	7347 ± 1237	6125 ± 1738	6078 ± 911
t1/2 (h)	2.08 ± 0.49	1.72 ± 0.23	1.93 ± 0.15	1.80 ± 0.16	1.39 ± 0.19
MRT (h)	1.82 ± 0.14	2.19 ± 0.43	1.48 ± 0.12	1.83 ± 0.45	1.73 ± 0.06
CLZ N-oxide
Cmax (nM)	214 ± 57.4	191 ± 32.7	196 ± 22.0	237 ± 69.5	200 ± 46.9
Tmax (h)	0.30 ± 0.05	0.29 ± 0.04	0.25 ± 0	0.31 ± 0.06	0.25 ± 0
AUC0-∞ (nM∙h)	146 ± 20.1	199 ± 48.5	182 ± 7.41	172 ± 39.9	159 ± 34.0
t1/2 (h)	0.55 ± 0.05	0.87 ± 0.12	0.61 ± 0.03	0.63 ± 0.12	0.44 ± 0.02
MRT (h)	0.91 ± 0.11	1.26 ± 0.22	0.82 ± 0.04	1.00 ± 0.26	0.72 ± 0.02

^a. Data are expressed as mean ± SEM and analyzed using one-way ANOVA. ^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.