Afro-Americans might have a higher clearance of olanzapine, due to a high prevalence of a SNP of CYP3A43. Olanzapine clearance was associated with measures of clinical response: Patients with greater clearance had higher symptom ratings and were more likely to discontinue treatment due to an inadequate response. In the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) (n=336, 60% Caucasian, 36% African American) the authors identified a single nucleotide polymorphism in the drug metabolizing enzyme, cytochrome P450 3A43 that highly significantly predicted olanzapine clearance. At standard antipsychotic doses, 50% of individuals with the high clearance genotype (AA) have trough blood levels below the therapeutic range. A much higher proportion of African Americans (67%) carry the A allele compared with Caucasians (14%). After accounting for CYP3A43 genotype, race is no longer a significant predictor of olanzapine clearance. The authors identified a genetic mechanism for variation in olanzapine response and demonstrate that blood level monitoring of olanzapine treatment is advisable (Bigos et al., 2011).

Pharmacokinetics USA Afro-Americans

Toxicity
Afro-Americans (n=12) had increased reports of side effects compared to Caucasians (p < 0.05).
Liberation
 
Administration/absorption
 
Distribution
Afro-Americans (n=12) had higher Lithium 'RedBloodCount/plasma' ratio (LR) compared to Caucasians (p < 0.05).
Metabolism

 

CYP1A2

 


CYP3A

 


CYP2B6

 


CYP2C8

 


CYP2C9

 


CYP2C19

 


CYP2D6

 

Excretion