The significance of sampling time in therapeutic drug monitoring of clozapine
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The significance of sampling time in therapeutic drug monitoring of clozapine. / Jakobsen, M I; Larsen, J R; Svensson, C K; Johansen, S S; Linnet, K; Nielsen, J.; Fink-Jensen, A.
I: Acta Psychiatrica Scandinavica, Bind 135, Nr. 2, 02.2017, s. 159-169.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - The significance of sampling time in therapeutic drug monitoring of clozapine
AU - Jakobsen, M I
AU - Larsen, J R
AU - Svensson, C K
AU - Johansen, S S
AU - Linnet, K
AU - Nielsen, J.
AU - Fink-Jensen, A
N1 - © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
PY - 2017/2
Y1 - 2017/2
N2 - 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.
AB - 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.
U2 - 10.1111/acps.12673
DO - 10.1111/acps.12673
M3 - Journal article
C2 - 27922183
VL - 135
SP - 159
EP - 169
JO - Acta Psychiatrica Scandinavica
JF - Acta Psychiatrica Scandinavica
SN - 0001-690X
IS - 2
ER -
ID: 171999854