Population Pharmacokinetics of Clozapine: A Systematic Review

Table 1

Studies’ population characteristics, samples, and concentrations.

Study	N (male/female)	Samples/subject	Total samples	Age (y^a)	Body weight (kg^a)	Site	Subjects characteristics	Dose (mg/day^a)	Samples’ time (h)	Clozapine concentration^a (ng/mL)	Norclozapine concentration^a (ng/mL)
Choc et al. [15]	13 (13/0)	33	429	34.2 ± 6.8	78 ± 11.7	USA and Georgia	Schizophrenia	150	0, 0.5, 1, 2, 4, 6, 9, 12	Cmin = 142.1; Cmax = 292.7	NA
Jerling et al. [16]	241 (159/82)	1.6	391	38 ± 10	NA	Sweden	Psychiatric patients	385	Random	Cx = 394.9	NA
Guitton et al. [17]	18 (13/5)	8	144	31 ± 9	70 ± 13.5	France	Schizophrenia	278	0, 0.5, 1, 2, 3, 5, 8, 12	Cmin = 400.5; Cmax = 914.5	Cmin = 240; Cmax = 377
Daily et al. [18]	23 (14/9)	3.6	83	37.6 ± 6.9	73.1 ± 14.7	France	Schizophrenia	540	Trough	NA	NA
Doude van Troostwijk et al. [19]	22 (19/4)	1	22	(28–64)	NA	Netherlands	Schizophrenia	426	Trough	C0 = 496 ± 220	C0 = 262 ± 107
Ng et al. [20]	197 (138/59)	2.6	519	38 ± 13	80.8 ± 18.5	Canada	Schizophrenia 98%	NA	Random	NA	NA
Qiu et al. [21]	183 (108/75)	3.4	626	49.7 ± 11.3	70.2 ± 11.9	China	Schizophrenia	289	Random	NA	NA
Ismail et al. [22]	391 (278/113)	2.9	1142	38.5 ± 12.4	82.5 ± 19.5	Canada	Schizophrenia	291	Random	Cx = 522.9 ± 326.8	Cx = 308.0 ± 172.4
Li et al. [23]	162 (74/88)	9.9	1617	35.5 ± 10.6	NA	China	Schizophrenia	NA	Random	Cx = 373 ± 239	Cx = 169 ± 100
Shang et al. [24]	198 (125/73)	7	1391	35 (18–59)	NA	China	Schizophrenia	(50–800)	Random	NA	NA
Li et al. [25]	47 (25/22)	3.3	154	37 (18–66)	67 (40–105)	China	Psychiatric patients	134	Trough	C0 = (309–4551)	NA
Olmos et al. [26]	98 (76/22)	1.7	171	39 [20–68]	78 [48–137]	Uruguay	Schizophrenia	350	Trough	C0 = 421 ± 262	C0 = 275 ± 180

C_min: minimum concentration; C_max: maximum concentration; C_x: random concentration; C₀: trough concentration; NA: not available. ^aValues are mean, mean ± standard deviation, mean (range), or median [range].