Gender differences in plasma clozapine levels and its metabolites in schizophrenic patients

Jann, Michael W.; Liu, Hui Ching; Wei, Fu Chuan; Lin, Shi Kwang; Lin, Shih Ku; Hu, Wei; Chang, Wen Ho

doi:10.1002/(sici)1099-1077(199709/10)12:5<489::aid-hup911>3.0.co;2-8

Cited by 16 publications

(10 citation statements)

References 25 publications

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“…[16]. In our sample, an increase in CLZ and NCLZ plasma concentrations was observed in women (about +18–26%) compared with men, a figure slightly lower than the ∼ +35–50% reported in much of the literature, for CLZ only [4, 5] and for CLZ and its metabolites combined [12, 20, 36]. In contrast, Perry et al.…”

Section: Discussioncontrasting

confidence: 72%

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Gender, age, smoking behaviour and plasma clozapine concentrations in 193 Chinese inpatients with schizophrenia

Tang

Mao

Li³

et al. 2007

Brit J Clinical Pharma

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What is already known about this subject • Plasma concentrations of clozapine (CLZ) and its active metabolite vary considerably at a given dosage.• A number of patient-related factors have been reported to increase the variability of plasma CLZ concentrations, with gender, age and smoking behaviour representing some of the more important contributing variables • However, results of previous studies concerning these factors have been inconsistent and most studies were conducted in western populations.What this study adds • Using this ethnically unique, relatively large sample, we replicated some findings in western populations, including large interindividual variability of plasma CLZ concentrations, significant effects of gender on plasma CLZ concentrations.• Female patients had significantly higher levels than males and no significant differences in plasma CLZ concentrations were observed between male smokers and nonsmokers, despite the CLZ dosage for smokers being significantly higher. AimTo study the relationship between age, gender, cigarette smoking and plasma concentrations of clozapine (CLZ) and its metabolite, norclozapine (NCLZ) in Chinese patients with schizophrenia. MethodsData 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 (Յ40 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 Ϯ 24.86 vs. 19.87 Ϯ 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 Յ40 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. ConclusionsPlasma 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.

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Section: Discussioncontrasting

confidence: 72%

“…However, results of previous studies concerning the effects of gender, age and smoking behaviour have been inconsistent. Some early studies demonstrated that women have higher concentrations of CLZ and NCLZ [4, 5, 12, 19, 20], but other studies have not been able to replicate this [6, 21, 22]. Fabrazzo et al.…”

mentioning

confidence: 99%

Gender, age, smoking behaviour and plasma clozapine concentrations in 193 Chinese inpatients with schizophrenia

Tang

Mao

Li³

et al. 2007

Brit J Clinical Pharma

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“…Pour certaines substances, la regle peut meme etre inversee : le sexe feminin est ainsi un facteur de mauvaise reponse au traitement par clozapine chez des patients refractaires aux autres neuroleptiques (28). Son efficacite dans l'amelioration des symptomes negatifs est egalement superieure chez les hommes (29). Bien qu'il n'existe pas d'etude precise a ce sujet, il semble que des resultats similaires puissent survenir avec la risperidone (30).…”

Section: N Euroleptiquesunclassified

“…Bien qu'il n'existe pas d'etude precise a ce sujet, il semble que des resultats similaires puissent survenir avec la risperidone (30). Ces molecules sont cependant responsables d'un faible taux d'effets secondaires extrapyramidaux, quel que soit le sexe (29,31). D'un point de vue pharmacologique, on sait que pour une meme dose par kilogramme de poids corporel, le taux plasmatique des neuroleptiques est plus eleve chez la femme, et leur clairance significativement plus basse (10).…”

Section: N Euroleptiquesunclassified

“…D'un point de vue pharmacologique, on sait que pour une meme dose par kilogramme de poids corporel, le taux plasmatique des neuroleptiques est plus eleve chez la femme, et leur clairance significativement plus basse (10). Ceci se verifie aussi pour la clozapine et ses metabolites (29), ainsi que pour le sertindole (32). vol 44,no4 Il existe une controverse quant ala frequence selon le sexe des dyskinesies tardives post-neuroleptiques.…”

Section: N Euroleptiquesunclassified

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Des variations intersexuelles relatives aux traitements en psychiatrie

Godfroid¹

1999

Can J Psychiatry

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A systematic review and meta-analysis of the association between clozapine and norclozapine serum levels and peripheral adverse drug reactions

et al. 2021

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Gender differences in plasma clozapine levels and its metabolites in schizophrenic patients

Cited by 16 publications

References 25 publications

Gender, age, smoking behaviour and plasma clozapine concentrations in 193 Chinese inpatients with schizophrenia

Gender, age, smoking behaviour and plasma clozapine concentrations in 193 Chinese inpatients with schizophrenia

Des variations intersexuelles relatives aux traitements en psychiatrie

A systematic review and meta-analysis of the association between clozapine and norclozapine serum levels and peripheral adverse drug reactions

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