The significance of sampling time in therapeutic drug monitoring of clozapine

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

M I Jakobsen, J R Larsen, C K Svensson, S S Johansen, K Linnet, J. Nielsen, A Fink-Jensen

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.

TidsskriftActa Psychiatrica Scandinavica
Udgave nummer2
Sider (fra-til)159-169
Antal sider11
StatusUdgivet - feb. 2017

ID: 171999854