OBJECTIVE: Cigarette smoking has been shown in several studies to induce the metabolism of the cytochrome P4501A2 (CYP1A2) substrates clozapine and olanzapine. The aim of the present study was to investigate the dose-dependent effect of cigarette smoking on serum concentrations of these drugs in a naturalistic setting. METHODS: In 73 schizophrenic patients recruited from psychiatric nursing homes, patient characteristics, smoking habits, drug dosing and serum concentrations of clozapine (n=33) and olanzapine (n=40) were registered. Concentration to dose (C/D) ratios of clozapine and olanzapine in non-smokers and subgroups of smokers were compared. RESULTS: Fifty-nine patients (80%) were smokers and these were stratified into the following groups according to smoking habits: 1-6 (n=0), 7-12 (n=13), 13-19 (n=18) and >or=20 (n=28) cigarettes daily. While the mean ratio was twice as high in non-smokers compared to smokers for both drugs (p<0.01), the C/D ratios of clozapine and olanzapine were not significantly different between the subgroups of smokers (p >0.15). Absolute serum concentrations were also higher in non-smokers compared to smokers: 50% for clozapine (p=0.058) and 67% for olanzapine (p<0.01). CONCLUSION: A daily consumption of 7-12 cigarettes is probably sufficient for maximum induction of clozapine and olanzapine metabolism. A 50% lower starting dose of both drugs in non-smokers seems rational to avoid side effects.
OBJECTIVE: Cigarette smoking has been shown in several studies to induce the metabolism of the cytochrome P4501A2 (CYP1A2) substrates clozapine and olanzapine. The aim of the present study was to investigate the dose-dependent effect of cigarette smoking on serum concentrations of these drugs in a naturalistic setting. METHODS: In 73 schizophrenicpatients recruited from psychiatric nursing homes, patient characteristics, smoking habits, drug dosing and serum concentrations of clozapine (n=33) and olanzapine (n=40) were registered. Concentration to dose (C/D) ratios of clozapine and olanzapine in non-smokers and subgroups of smokers were compared. RESULTS: Fifty-nine patients (80%) were smokers and these were stratified into the following groups according to smoking habits: 1-6 (n=0), 7-12 (n=13), 13-19 (n=18) and >or=20 (n=28) cigarettes daily. While the mean ratio was twice as high in non-smokers compared to smokers for both drugs (p<0.01), the C/D ratios of clozapine and olanzapine were not significantly different between the subgroups of smokers (p >0.15). Absolute serum concentrations were also higher in non-smokers compared to smokers: 50% for clozapine (p=0.058) and 67% for olanzapine (p<0.01). CONCLUSION: A daily consumption of 7-12 cigarettes is probably sufficient for maximum induction of clozapine and olanzapine metabolism. A 50% lower starting dose of both drugs in non-smokers seems rational to avoid side effects.
Authors: P Baumann; C Hiemke; S Ulrich; I Gaertner; M L Rao; G Eckermann; M Gerlach; H J Kuss; G Laux; B Müller-Oerlinghausen; P Riederer; G Zernig Journal: Ther Drug Monit Date: 2004-04 Impact factor: 3.681
Authors: Paul J Perry; Tami R Argo; Ryan M Carnahan; Brian C Lund; Timothy L Holman; Vicki L Ellingrod; Del Miller Journal: J Clin Psychopharmacol Date: 2005-06 Impact factor: 3.153
Authors: Jaimee L Heffner; Jeffrey R Strawn; Melissa P DelBello; Stephen M Strakowski; Robert M Anthenelli Journal: Bipolar Disord Date: 2011 Aug-Sep Impact factor: 6.744
Authors: Christina P C Borba; Xiaoduo Fan; Paul M Copeland; Alexander Paiva; Oliver Freudenreich; David C Henderson Journal: J Clin Psychopharmacol Date: 2011-10 Impact factor: 3.153
Authors: Eunkyoung Kim; Yi Liu; Hadar Ben-Yoav; Thomas E Winkler; Kun Yan; Xiaowen Shi; Jana Shen; Deanna L Kelly; Reza Ghodssi; William E Bentley; Gregory F Payne Journal: Adv Healthc Mater Date: 2016-09-12 Impact factor: 9.933