Population Pharmacokinetics of Clozapine and Norclozapine and Switchability Assessment between Brands in Uruguayan Patients with Schizophrenia

Table 2

Estimates of population pharmacokinetic analysis of clozapine and norclozapine trough plasma levels in schizophrenic patients.

Parameter	Description	Final model; estimate (RSE%)	Shrinkage	Bootstrap results (n=200)
				Mean	RSE%	Median	95% CI
Population Mean
(L/h)	Clozapine apparent elimination clearance in nonsmokers	28.1 (6)	-	27.8	5.6	27.8	24.7	31.1
SMK (L/h)	Clozapine apparent elimination clearance in smokers	36.5 (8)	-	36.9	7.9	36.9	30.5	42.8
(L/h)	Norclozapine apparent elimination clearance	53.6 (6)	-	53.5	6.5	53.5	46.7	60.2
F Luverina	Relative bioavailability of Luverina® versus Leponex®	0.892 (6)	-	0.895	6.8	0.896	0.769	1.02
Between-subject CV
BSV (%)		43.3 (12)	14	43.3	22	43.3	31.8	53.6
BSV (%)		49.9 (12)	18	50.3	26	50.4	35.9	64.2
BSV F (%)		43.6 (17)	26	43.9	34	43.9	24.7	58.9
cov - (%)		55.7 (30)	-	34.1	26	34.1	24.0	43.2
Residual variability
Proportional clozapine (%)		9.54 (21)	30	9.29	27	9.52	2.97	13.4
Proportional norclozapine (%)		15.3 (15)	22	15.3	16	15.2	10.8	20.3