Abstract
Inter-racial differences in serum clozapine have received less scientific importance, as there are fewer studies on therapeutic drug monitoring (TDM) from Asia. We measured the serum clozapine levels in 142 patients with schizophrenia and related disorders at a tertiary care psychiatric institute in India. The clozapine concentration per milligram (mg) of oral clozapine dose (C/D ratio) was calculated, and the C/D ratio was used to estimate oral clozapine dose needed to achieve therapeutic serum clozapine level (350 ng/ml). This study examined Indian patients only and compared the results with weighted mean serum clozapine and its correlates in Caucasian population, based on published scientific literature. The median C/D ratio in our sample was 2.5 (n = 142), and the clozapine dose needed to achieve therapeutic serum clozapine level was 140 mg/d. The median C/D ratio of our subjects was nearly two and a half times higher than the weighted mean C/D ratio of Caucasians (2.5 v/s 1.07) reported elsewhere. After excluding the significant pharmacokinetic interactions and stratifying according to gender and smoking status, the estimated clozapine dose to achieve therapeutic serum level in male smokers (n = 9) and female non-smokers (n = 38) were 238 mg/d (C/D ratio; 1.47) and 120 mg/d (C/D ratio:2.93) respectively. On comparing, male smokers (600 mg/d versus 238 mg/d) and female non-smokers (300 mg/d versus 120 mg/d) in our study needed about 40% of the recommended clozapine dose for Caucasians to achieve therapeutic serum clozapine level. The pharmacogenetic correlates of lesser clozapine dose requirement in the Indian population require further research.
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