Fluorescence of neutrophil granulocytes as a biomarker for clozapine use.
Non-adherence to medication is a major issue in the treatment of schizophrenia in general and in particular for those treated with clozapine. A reliable tool to quantify patients long-term adherence to clozapine is currently unavailable. Enhanced FL3 neutrophil granulocyte fluorescence was serendipitously observed in a small population of schizophrenic patients treated with clozapine. The present study was aimed at assessing the association between clozapine use and FL3-fluorescence. A cross-sectional study was performed using data from the Utrecht Patient Oriented Database (UPOD). A total of 38,390 inpatients were included, of which 124 (0.33%) used clozapine. FL3-fluorescence was significantly higher (U=240,179, P<0.001) in clozapine users (mean (SD)=90.5 (11.8)) than in non-users (mean (SD)=69.8 (3.3)). Observed FL3-fluorescence was found to increase with increasing clozapine dose. The area under the receiver operating characteristic curve was 0.95. Our results confirm the association between use of clozapine and elevated FL3-fluorescence. Further research is needed to unravel the underlying mechanism and to investigate the true potential of FL3-fluorescence as a clozapine-adherence biomarker in clinical practice.
Department of Clinical Pharmacy, University Medical Center Utrecht, The Netherlands.
Wai Hong
WH
Man
Maarten
M
Ten Berg
Ingeborg
I
Wilting
Albert
A
Huisman
Wiepke
W
Cahn
Jan Willem
JW
Douma
Hanneke
H
den Breeijen
Eibert R
ER
Heerdink
Toine
T
Egberts
Wouter
W
van Solinge
D000328:Adult; D054316:Biomarkers, Pharmacological / Q000097:blood*; D003024:Clozapine / Q000008:administration & dosage* / Q000494:pharmacology* / Q000627:therapeutic use; D003430:Cross-Sectional Studies; D062313:Databases, Pharmaceutical; D004305:Dose-Response Relationship, Drug; D005260:Female; D005453:Fluorescence; D005456:Fluorescent Dyes / Q000032:analysis; D006801:Humans; D008163:Luminescent Measurements / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000737:chemistry / Q000187:drug effects*; D010349:Patient Compliance; D012372:ROC Curve; D012559:Schizophrenia / Q000097:blood / Q000188:drug therapy*; D012680:Sensitivity and Specificity
D054316:Biomarkers, Pharmacological; D005456:Fluorescent Dyes; D003024:Clozapine
Biomarker; Clozapine; FL3-fluorescence; Medication adherence; Neutrophil granulocytes; Schizophrenia