The significance of sampling time in therapeutic drug monitoring of clozapine

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Abstract

Objective:

Therapeutic drug monitoring (TDM) of clozapine is standardized to 12-h postdose samplings. In clinical settings, sampling time often deviates from this time point, although the importance of the deviation is unknown. To this end, serum concentrations (s-) of clozapine and its metabolite N-desmethyl-clozapine (norclozapine) were measured at 12 ± 1 and 2 h postdose.

Method:

Forty-six patients with a diagnosis of schizophrenia, and on stable clozapine treatment, were enrolled for hourly, venous blood sampling at 10–14 h postdose.

Results:

Minor changes in median percentage values were observed for both s-clozapine (−8.4%) and s-norclozapine (+1.2%) across the 4-h time span. Maximum individual differences were 42.8% for s-clozapine and 38.4% for s-norclozapine. Compared to 12-h values, maximum median differences were 8.4% for s-clozapine and 7.3% for s-norclozapine at deviations of ±2 h. Maximum individual differences were 52.6% for s-clozapine and 105.0% for s-norclozapine. The magnitude of s-clozapine differences was significantly associated with age, body mass index and the presence of chronic basophilia or monocytosis.

Conclusion:

The impact of deviations in clozapine TDM sampling time, within the time span of 10–14 h postdose, seems of minor importance when looking at median percentage differences. However, substantial individual differences were observed, which implies a need to adhere to a fixed sampling time.

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