Asian patients from Singapore (n=20) have a lower dosage requirement for clinical efficacy compared to Caucasian patients (from Australia) (n=20) with chronic schizophrenia who were on stable maintenance treatment. Asian patients needed a significantly lower mean clozapine dose (176 mg/day) than the Caucasian group (433 mg/day, P<0.001) to acquire similar plasma clozapine levels between the groups. Asian patients from Singapore had more than twice the effective clozapine concentration to dose ratio (P<0.001) and remained significant after controlling for gender, body mass index, cigarette, alcohol and caffeine use. Conversely, the plasma metabolites (desmethylclozapine and clozapine N-oxide) to clozapine ratios were higher in the Caucasian patients (P<0.01). (Ng et al, 2005)

Consider: appropriate dose adjustment in Asian patients receiving maintenance clozapine therapy.

Pharmacokinetics Singapore

Toxicity
Carbamazepine: Patients from Singapore have increased rates of carrying HLA-B*1502. Patients carrying HLA-B*1502 are at strongly increased risk for carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN). Odds Ratio for SJS/TEN among Singaporese children (of Chinese and Malay ethnicity) is 27.20 (95% CI 2.67 to 8) (Chong, 2014).
Liberation
 
Administration/absorption
 
Distribution
 
Metabolism

 

CYP1A2

 


CYP3A

 


CYP2B6

 


CYP2C8

 


CYP2C9

 


CYP2C19

 


CYP2D6

 

Excretion