Effects of paroxetine on aripiprazole and individualized administration in depressed patients based on model-informed precision dosing

Table 1 Demographic data of depressed patients with aripiprazole (n = 87), mean ± SD

Characteristic	mean ± SD	Median (range)
Gender (men/women)	30/57	-
Age (years)	25.81 ± 14.18	20.06 (12.73-72.21)
Weight (kg)	65.49 ± 16.81	60.00 (40.00-108.00)
Albumin (g/L)	42.30 ± 3.19	42.20 (35.30-50.00)
Globulin (g/L)	26.21 ± 3.52	25.90 (19.10-40.60)
Alanine transaminase (IU/L)	24.28 ± 16.27	20.00 (6.00-101.00)
Aspartate transaminase (IU/L)	20.83 ± 9.57	18.00 (10.00-70.00)
Creatinine (μmol/L)	59.18 ± 13.76	56.00 (38.00-93.00)
Urea (mmol/L)	4.26 ± 1.17	4.12 (2.24-7.66)
Total protein (g/L)	68.51 ± 4.67	68.00 (59.90-83.60)
Triglyceride (mmol/L)	1.59 ± 1.02	1.19 (0.28-4.47)
Direct bilirubin (μmol/L)	2.73 ± 1.13	2.60 (0.40-6.00)
Total bilibrubin (μmol/L)	8.58 ± 3.81	8.00 (2.30-26.70)
Hematocrit (%)	40.04 ± 4.41	39.80 (31.10-49.10)
Hemoglobin (g/L)	133.16 ± 16.78	130.00 (99.00-169.00)
Mean corpuscular hemoglobin (pg)	29.84 ± 2.06	30.00 (21.50-34.10)
Mean corpuscular hemoglobin concentration (g/L)	332.10 ± 11.21	333.00 (302.00-359.00)

Table 2 Drug combination in depressed patients with aripiprazole (n = 87)

Drug	Category	n	Drug	Category	n
Acarbose capsule	0	86	Liver-protecting tablet	0	86
	1	1		1	1
Alprazolam tablet	0	73	Lorazepam tablet	0	75
	1	14		1	12
Bezafibrate	0	86	Metformin hydrochloride tablet	0	83
	1	1		1	4
Clonazepam tablet	0	74	Mirtazapine tablet	0	84
	1	13		1	3
Duloxetine hydrochloride enteric-coated capsule	0	80	Olanzapine tablet	0	80
	1	7		1	7
Escitalopram oxalate tablet	0	84	Paroxetine hydrochloride tablet	0	73
	1	3		1	14
Fluvoxamine maleate tablet	0	86	Propranolol hydrochloride tablet	0	81
	1	1		1	6
Irbesartan hydrochlorothiazide tablet	0	86	Sanhuang tablet	0	85
	1	1		1	2
Levothyroxine sodium tablet	0	84	Sertraline hydrochloride tablet	0	44
	1	3		1	43
Lithium carbonate extended-release tablet	0	74	Xuesaitong for injection	0	86
	1	13		1	1

Sanhuang tablet is a traditional Chinese medicine that has the effects of clearing heat, reducing fire, detoxifying and promoting defecation. Category 0: Without drug, Category 1: With drug; n: Number of patients.

Table 3 Parameter estimates of aripiprazole final model and bootstrap validation in depressed patients

Parameter	Estimate	SE (%)	Bootstrap
			Median	95%CI
CL/F (L/hour)	3.12	7.6	3.14	2.70-3.70
V/F (L)	287	5.5	284	66-327
Ka (hour-1)	1.06 (fixed)	-	-	-
θPAR	-0.533	16.9	-0.534	-0.696 to -0.189
ωCL/F	0.489	18.6	0.479	0.299-0.699
σ1	42.426	18.2	39.749	20.847-55.946

95% confidential interval was displayed as the 2.5^th, 97.5^th percentile of bootstrap estimates. CL/F: Apparent oral clearance; V/F: Volume of distribution; Ka: Absorption rate constant; θ_PAR: The coefficient of paroxetine hydrochloride tablet; ω_CL/F: Inter-individual variability of apparent oral clearance; σ₁: Residual variability, additive error; CI: Confidence interval.

Table 4 Initial dosage recommendation of aripiprazole in depressed patients

Without paroxetine hydrochloride tablet			With paroxetine hydrochloride tablet
Body weight (kg)	Dosage (mg/kg/day)	Probability to achieve the target concentrations (%)	Body weight (kg)	Dosage (mg/kg/day)	Probability to achieve the target concentrations (%)
40-80	0.5	99.4-99.8	40-120	0.3	99.7-100
80-120	0.4	99.3-99.5	-	-	-