Clozapine-Induced Severe Toxicity: Exploring the Pharmacokinetic Profile of Clozapine and Its Significance in Hemodynamic Instability – A Case Report

Figures & data

Figure 1 Electrocardiography of the patient on admission.

Table 1 The First PICCO Hemodynamic Monitoring Results

Parameter	Monitoring Results	Normal Range
CI (L/min/m^2)	9.63	3.0–5.5
ITBVI (mL/m^2)	1001	850–1000
GEDVI (mL/m^2)	801	680–200
SVRI (dyn*s*cm^−5*m^2)	365	1200–2000
EVLWI (mL/m^2)	11.4	3.0–7.0
SVI (mL/m^2)	64.6	40–60
GEF	34%	25–35%
dPmax (mmHg/s)	984	1200–2000
LVSWI (kg/min.m^2)	54.5	40–60
SVV	8%	≤10%
HR(bpm)	149	60–100
ABP(MAP)(mmHg)	110/42 (62)	70–90
CVP(mmHg)	18	2–10
ScvO2	81%	60–80%

Table 2 The Patients Were Monitored by PICCO Hemodynamics and the Dosage of the Vasopressors Drugs

		Day2	Day3	Day4	Day5	Day6	Day7	Day8	Day9
CI		9.63	8.21	6.54	5.79	4.8	5.2	5.02	4.86
ITBVI		1001	963	1003	834	797	961	820	737
GEDVI		801	771	803	667	638	689	656	590
SVRI		365	575	807	773	1000	1092	1034	953
EVLWI		11.4	1.1	12.4	9	9.7	8.8	8.5	8.1
SVI		64.6	63.6	55.9	53.6	50.5	59.1	86.6
CFI				8.6	9.1	7.9	8	8.1	8.7
GEF		34%	35%	30%	34%	35%	36%	35%	36%
dPmax		984	879	1066	814	639	1243	986	838
LVSWI		54.5	61.5	64.6	52.5	52.5	66.7	82.4	41.9
SVV		8%		20%	11%	24%	9%	15%
HR		149	129	117	108	95	88	94	98
ABP(MAP)		110/42 (62)	113/71	122/69 (85)	103/58 (72)	114/72 (78)	131/65 (83)	107/54 (70)	61
CVP		18	12	19	16	15	12	5	4
ScvO2		81%	87.7%			86.7%		88%
Vasopressors	Norepinephrine (ug/kg/min)	0.46	1.6	1.2	0.4	0.06	0.04	0	0
	Terlipressin (Unit/min)	0	0.05	0.05	0.05	0.03	0.017	0	0
Antiarrhythmic drugs	Esmolol (mg/kg/min)	0.1	0.17	0.17	0.11	0.06	0	0	0

Figure 2 Electrocardiography of the patient showing sinus tachycardia about 24 hours after taking clozapine.

Figure 3 The serum concentrations of clozapine and norclozapine during hospitalization.

Table 3 The Clozapine Levels and the VDI Index During Hospitalization

The Serum Concentrations of Clozapine (ng/mL)	VDI Index
5930.75	0.2
3589.22	2.2
2816.94	1.712329
2140.98	1.582278
1876.49	1.193182
2954.39	0.872093
1780.15	0.529412
2316.28	0.602273
1769.08	0.244681
781.44	0.064773
768.88	0.072826
132.23	0.052632
98.19	0.028169
67.83	0.089552

Notes: VDI is calculated as following: .Epinephrine, norepinephrine, dobutamine, and dopamine are expressed as µg/kg/min and vasopressin as units/min.

Figure 4 The clozapine levels and the VDI index during hospitalization.

Figure 5 A positive correlation between VDI index and serum concentration of clozapine.

Data Sharing Statement

Patient data supporting the results reported in the article can be obtained from the corresponding author by email.