Couchman L et al. – As in adults, clozapine therapeutic drug monitoring may help in assessing adherence and in dose adjustment, for example if smoking habit changes.

• The authors studied data from a clozapine therapeutic drug monitoring (TDM) service, patients in the UK and Eire aged <18 years, 1994-2010.
• Multiple linear regression analysis was performed to investigate the relationship between plasma clozapine concentration and dose, age, sex, body weight, plasma clozapine:norclozapine ratio (clozapine metabolic ratio (MR)) and smoking habit.

• There were 1408 samples from 454 patients, 267 (59%) males aged at time of first sample (median = 17; range = 8-17 years) and 187 (41%) females aged 16 (10-17) years.
• The plasma clozapine concentration was <0.35 mg L-1 in 36%, and ≥0.60 mg L-1 in 31% of samples (6.4% samples ≥1.0 mg L-1).
• Although plasma clozapine was broadly related to prescribed dose, there was much variation: 10% of samples had plasma clozapine >0.60 mg L-1 at prescribed clozapine doses of 50-150 mg d-1 (66% <0.35 mg L-1), while 12% of samples had plasma clozapine <0.35 mg L-1 at doses ≥650 mg d-1 (62% >0.6 mg L-1).
• The covariates studied in the 16-17-year-olds had proportionately similar influences to those observed in adults.
• Together they explained 48% of the variance observed in plasma clozapine, with dose, smoking habit, MR and sex being major influences.
• In the younger patients, there were very few smokers, and the influence of sex did not reach statistical significance.