Possible impact of the CYP2D6*10 polymorphism on the nonlinear pharmacokinetic parameter estimates of paroxetine in Japanese patients with major depressive disorders

Figures & data

Table 1 The clinical characteristics of the plasma paroxetine concentrations and the observed pharmacokinetic parameters in all patients, CYP2D6*10 allele carriers, and CYP2D6*10 noncarriers

	All patients (n=15)	CYP2D6*10 allele carriers (n=11)	CYP2D6*10 allele noncarriers (n=4)	P-valuea
Age (years)	43.4±18.3	36.5±14.9	62.5±12.7	0.010
Sex (M, male; F, female)	M=4, F=11	M=2, F=9	M=2, F=2	0.516
Body weight (kg)	58.1±11.8	60.3±11.3	52.3±12.7	0.733
Daily paroxetine dose (mg)	29.1±11.3	31.5±9.9	28.4±11.7	0.392
Blood sampling time after the last paroxetine dose (hour)	13.5±3.4	13.5±3.1	13.5±3.5	0.922
The number of blood samples collected per patient	3.7±0.7	3.9±0.7	3.3±0.5	0.144
Plasma paroxetine concentration (ng/mL)	74.4±73.7	116.6±124.5	61.7±44.3	0.122
Plasma paroxetine concentration corrected for dose (ng/mL/mg)	2.4±1.9	3.5±3.1	2.1±1.2	0.159
Km (ng/mL)	50.5±68.4	24.2±18.3	122.5±106.3	0.008
Vmax (mg/day)	50.6±18.8	44.2±16.1	68.2±15.0	0.022

Note:

a Compared between the CYP2D6*10 allele carriers and the noncarriers by the Mann–Whitney U-test or by Fisher’s exact test.

Abbreviations: K_m, Michaelis–Menten constant; V_max, maximum velocity.

Figure 1 Individual and mean values of the nonlinear pharmacokinetic parameters, K_m (A) and V_max (B), of paroxetine in the CYP2D6*10 allele carriers and the noncarriers, respectively.

Abbreviations: K_m, Michaelis–Menten constant; V_max, maximum velocity.

Figure 2 The simulation of the relationships between the plasma concentrations and the daily doses of paroxetine between the CYP2D6*10 allele carriers and the noncarriers based on the pharmacokinetic parameters observed in this study.

Figure 3 Individual and mean values of the plasma concentration in each daily dose of paroxetine among the CYP2D6*10 allele carriers (solid circles) and the noncarriers (open circles).