Effect of sodium valproate on aripiprazole pharmacokinetics and initial dosage optimization in bipolar disorder

Table 1 Demographic data of bipolar disorder patients receiving aripiprazole (n = 24)

Characteristic	mean ± SD	Median (range)
Gender (men/women)	15/9
Age (years)	36.55 ± 9.47	33.25 (18.05-66.50)
Weight (kg)	74.55 ± 12.03	75.00 (50.00-105.00)
Albumin (g/L)	43.06 ± 3.26	42.80 (36.10-49.80)
Globulin (g/L)	25.37 ± 3.04	24.80 (19.10-31.20)
Alanine transaminase (IU/L)	24.92 ± 14.41	21.00 (9.00-68.00)
Aspartate transaminase (IU/L)	18.78 ± 5.89	18.00 (11.00-41.00)
Creatinine (μmol/L)	64.33 ± 9.54	63.00 (44.00-88.00)
Urea (mmol/L)	3.93 ± 1.26	3.66 (2.12-7.50)
Total protein (g/L)	68.42 ± 4.66	68.90 (58.30-77.80)
Triglyceride (mmol/L)	2.25 ± 1.10	2.12 (0.71-6.65)
Direct bilirubin (μmol/L)	2.75 ± 1.30	2.50 (0.60-5.90)
Total bilirubin (μmol/L)	8.44 ± 3.40	8.30 (2.50-17.70)
Hematocrit (%)	41.57 ± 2.98	42.00 (34.50-46.90)
Hemoglobin (g/L)	137.63 ± 10.57	138.00 (115.00-155.00)
Mean corpuscular hemoglobin (pg)	31.05 ± 0.98	31.20 (29.10-33.70)
Mean corpuscular hemoglobin concentration (g/L)	330.96 ± 6.82	331.00 (314.00-344.00)

Table 2 Drug combination in bipolar disorder patients with aripiprazole (n = 24)

Drug	Category1	n	Drug	Category	n
Atorvastatin calcium tablets	0	22	Lithium carbonate extended-release tablets	0	11
	1	2		1	13
Alprazolam tablets	0	20	Lorazepam tablets	0	15
	1	4		1	9
Ambroxol hydrochloride oral solution	0	23	Metformin hydrochloride tablets	0	23
	1	1		1	1
Benhexol hydrochloride tablets	0	20	Olanzapine tablets	0	19
	1	4		1	5
Clonazepam tablets	0	19	Perphenazine tablets	0	21
	1	5		1	3
Clozapine tablets	0	20	Propranolol hydrochloride tablets	0	21
	1	4		1	3
Diazepam injection	0	22	Quetiapine fumarate tablets	0	20
	1	2		1	4
Escitalopram oxalate tablets	0	22	Sertraline hydrochloride tablets	0	23
	1	2		1	1
Finasteride tablets	0	23	Sodium valproate sustained-release tablets	0	14
	1	1		1	10
Haloperidol injection	0	23	Zolpidem tartrate	0	23
	1	1		1	1
Lamotrigine tablets	0	23	Zopiclone tablets	0	22
	1	1		1	2

¹Category, 0: Without drug, 1: With drug; n: Number of patients.

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

Parameter	Estimate	SE	Bootstrap
			Median	95% confidence interval1
CL/F (L/hour)	2.42	0.03	2.41	2.22-2.84
V/F (L)	425	0.16	439	174-581
Ka (hour-1)	1.06 (fixed)
θVPA2	0.667	0.16	0.643	0.163-0.911
ωV/F3	0.068	5.38	0.003	0.003-0.431
σ14	0.222	0.13	0.220	0.003-0.279
σ25	25.826	0.26	23.685	0.010-41.213

¹95% confidential interval is displayed as the 2.5^th, 97.5^th percentile of bootstrap estimates.

²θ_VPA is the coefficient of sodium valproate sustained-release tablet.

³ω_V/F, inter-individual variability of apparent volume of distribution.

⁴σ₁, residual variability, proportional error.

⁵σ₂, residual variability, additive error.

CL/F: Apparent oral clearance; V/F: Apparent volume of distribution; Ka: Absorption rate constant.

Table 4 Initial dosage recommendation of aripiprazole in patients with bipolar disorder

Patients not receiving sodium valproate sustained-release tablets		Patients receiving sodium valproate sustained-release tablets
Body weight (kg)	Dosage (mg/kg/day)	Body weight (kg)	Dosage (mg/kg/day)
40-120	0.3	40-120	0.4