@conference{
author = "Panić, Bojana and Jovanović, Marija and Lukić, Vera and Bulat, Zorica and Vučićević, Katarina and Miljković, Branislava and Milovanović, Srđan",
year = "2022",
abstract = "The atypical antipsychotic clozapine (CLZ) is primarily used for the treatment-
resistant schizophrenia. Due to low therapeutic index and high pharmacokinetic variability,
therapeutic drug monitoring (TDM) is highly recommended (1). The aim of this retrospective
study was to analyze TDM data of CLZ and its active metabolite norclozapine (NCLZ) in adult
patient with schizophrenia. The study included CLZ TDM data obtained from 69 patients (22-
67 years) treated at the Clinic for Psychiatry, Clinical Center of Serbia, while NCLZ data were
available from 43 patients. Serum concentrations were determined at the Institute of
Forensic Medicine, Belgrade, Serbia using liquid chromatography with tandem mass
spectrometry (LC‐MS/MS). Statistical analysis was performed by SPSS software® (version
18). The daily doses of CLZ ranged between 37.5 and 600 mg. The mean value of CLZ and
NCLZ levels were 0.285 ± 0.174 mg/L and 0.189 ± 0.132 mg/L, respectively. 73.06% and
26.83% of measured CLZ and NCLZ concentrations were outside reference range (mostly
below), respectively. Significant positive correlation (p<0.05) was observed between daily
dose and CLZ levels, as well as between dose and NCLZ levels. Significant correlations of dose
and CLZ levels were confirmed in males and females, smokers and nonsmokers, separately.
Parent drug and metabolite levels varied 13 and 16-fold in patients receiving 300 mg/day,
respectively. The results indicate considerable variability in CLZ and NCLZ concentrations in
adult patients with schizophrenia, and positive association with dose. Further multivariate
analysis is required to assess, in addition to dose, potential influences of other patient and
co-therapy factors., Atipični antipsihotik klozapin (clozapine, CLZ) se primarno koristi kod shizofrenije
rezistentne na terapiju. Zbog niskog terapijskog indeksa i velike farmakokinetičke
varijabilnosti, terapijsko prać enje lekova (therapeutic drug monitoring, TDM) se preporučuje
(1). Cilj ovog retrospektivnog istraživanja je bio ispitivanje TDM podataka o CLZ i njegovom
aktivnom metabolitu norklozapinu (norclozapine, NCLZ) kod odraslih pacijenata sa
shizofrenijom. Studija je obuhvatila TDM podatke o CLZ dobijene od 69 pacijenata (22-67
godina) lečenih na Klinici za psihijatriju Kliničkog centra Srbije, dok su podaci za NCLZ bili
dostupni od 43 pacijenta. Koncentracije u serumu su merene na Institutu za sudsku
medicinu, Beograd, Srbija tečnom hromatografijom sa tandem masenom spektrometrijom
(LC‐MS/MS). Statistička analiza je izvršena pomoć u softvera SPSS® (verzija 18). Dnevne doze
CLZ kretale su se između 37,5 i 600 mg. Srednja vrednost je bila 0,285 ± 0,174 mg/L za CLZ i
0,189 ± 0,132 mg/L za NCLZ. 73,06% i 26,83% izmerenih koncentracija CLZ i NCLZ bile su
izvan referentnog opsega (uglavnom ispod), respektivno. Detektovana je pozitivna korelacija
(p<0,05) između dnevne doze i nivoa CLZ, kao i doze i nivoa NCLZ. Značajna korelacija doze i
nivoa CLZ je potvrđena i pri odvojenom ispitivanju kod muškaraca, žena, pušača i nepušača.
Nivoi leka i metabolita varirali su 13 i 16 puta kod pacijenata koji su uzimali 300 mg/dan,
respektivno. Rezultati ukazuju na značajnu varijabilnost u koncentracijama CLZ i NCLZ kod
odraslih pacijenata sa shizofrenijom i pozitivnu povezanost sa dozom. Potrebna je dalja
multivarijantna analiza da bi se procenili, pored doze, potencijalni uticaji karakteristika
pacijenata i kombinovane terapije.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Analysis of clozapine and norclozapine concentrations in adult patients with schizophrenia, Analiza koncentracija klozapina i norklozapina kod odraslih pacijenata sa shizofrenijom",
volume = "72",
number = "4 suplement",
pages = "S225-S226",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4507"
}