Gender, age, smoking behaviour and plasma clozapine concentrations in 193 Chinese inpatients with schizophrenia.
OBJECTIVE
To study the relationship between age, gender, cigarette smoking and plasma concentrations of clozapine (CLZ) and its metabolite, norclozapine (NCLZ) in Chinese patients with schizophrenia.


METHODS
Data from a therapeutic drug monitoring programme were analysed retrospectively. One hundred and ninety-three Chinese inpatients with schizophrenia were assessed using clinical data forms. Steady-state plasma concentrations of CLZ and NCLZ were assayed using high-performance liquid chromatography. Comparisons of dosage and plasma CLZ concentrations were undertaken between males (n = 116) and females (n = 77), younger (<or=40 years, n = 82) and older patients (>40 years, n = 111) and current male smokers (n = 50) and nonsmokers (n = 66).


RESULTS
(i) Plasma CLZ concentrations demonstrated large interindividual variability, up to eightfold at a given dose; (ii) there were significant effects of gender on plasma CLZ concentrations (relative to dose per kg of body weight) with female patients having significantly higher concentrations than males (30.09 +/- 24.86 vs. 19.87 +/- 3.55 ng ml(-1) mg(-1) day(-1) kg(-1); P < 0.001); (iii) there were no significant differences in plasma CLZ concentrations between those patients <or=40 years old and those >40 years; and (iv) there were no significant differences in plasma CLZ concentrations between male smokers and nonsmokers, despite the CLZ dosage for smokers being significantly higher.


CONCLUSIONS
Plasma CLZ concentrations vary up to eightfold in Chinese patients. Among the patient-related factors investigated, only gender was significant in affecting CLZ concentrations in Chinese patients with schizophrenia, with female patients having higher levels.
Tang
Yi-lang
YL
Beijing Anding Hospital, Capital University of Medical Sciences, Beijing, China. ytang@genetics.emory.edu
Mao
Peixian
P
Li
Feng-Min
FM
Li
Wenbiao
W
Chen
Qi
Q
Jiang
Feng
F
Cai
Zhuo-ji
ZJ
Mitchell
Philip B
PB
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D014150:Antipsychotic Agents / Q000097:blood* / Q000627:therapeutic use; D044466:Asian People; D003024:Clozapine / Q000031:analogs & derivatives / Q000097:blood* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012559:Schizophrenia / Q000097:blood / Q000188:drug therapy*; D012737:Sex Factors; D012907:Smoking / Q000378:metabolism
D014150:Antipsychotic Agents; C058272:norclozapine; D003024:Clozapine