Table 5.

Genetic and Clinical Determinants of Blood Clozapine Concentration: Linear Regression Model Coefficients from Prospective Cohort of Patients Prescribed Clozapine.

Variable	Coefficient	P Value
Log(BMI)	1.221	0.0240*
Smoking	0.676	0.268
CYP2C19 IM	0.069	0.734
CYP2C19 PM	0.733	0.0579
CYP1A2*1F C/A	1.023	0.0746
CYP1A2*1F A/A	0.751	0.187
Smoker: CYP1A2*1F C/A	–1.372	0.0499*
Smoker: CYP1A2*1F A/A	–0.799	0.230
Adjusted R2		0.352

Outcomes were log transformed. Model adjusted for sex, age, and dose. Clozapine dose, as expected, was a significant determinant of the clozapine level in this model (P = 0.0004). Covariates considered included smoking, body mass index (BMI) (for level), and CYP1A2, CYP2C19, and ABCB1 genotypes. CYP1A2*1C (coefficient = 0.637, P = 0.272), CYP1A2*1D (coefficient = –0.099, P = 0.830), and ABCB1 c.3435 (coefficient = 0.142, P = 0.286) were not significant in our final model. CYP1A2*1F is represented by the more common A allele. The CYP2C19*1/*2 (n = 10) or *17/*2 (n = 2) genotype was combined as the CYP2C19 IM phenotype (intermediate metabolizer), *2/*2 (n = 3) as the CYP2C19 PM phenotype (poor metabolizer), and compared to *1/*1 (n = 27), *1/*17 (n = 17) as the CYP2C19 EM phenotype (extensive metabolizer). One patient with CYP2C19*17/*17 (UM or ultrarapid metabolizer) was added to the EM group. CYP2C19*1 denotes the reference or also wild-type allele, encoding an enzyme with normal function in a subject with the *1/*1 genotype.

*P < 0.05.