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The effect of variable cigarette consumption on the interaction with ...
Objective. Cigarette smoking has been shown in several studies to induce the metabolism of the cytochrome P4501A2 (CYP1A2) substrates clozapine and ...
Eur J Clin Pharmacol (2006) 62:1049–1053 DOI 10.1007/s00228-006-0209-9
PHARMACOKINETICS AND DISPOSITION
The effect of variable cigarette consumption on the interaction with clozapine and olanzapine Tore Haslemo & Per Haakon Eikeseth & Lars Tanum & Espen Molden & Helge Refsum
Received: 6 July 2006 / Accepted: 11 September 2006 / Published online: 7 November 2006 # Springer-Verlag 2006
Abstract 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 dosedependent 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 ≥20 (n=28) cigarettes daily. While the mean ratio was twice as high in non-smokers compared to smokers for both drugs (p0.15). Absolute serum concentrations were also higher in non-smokers compared to smokers: 50% for clozapine (p=0.058) and 67% for olanzapine (p0.7) between subgroups of smokers. Non-smokers had a two-fold higher C/D ratio compared to the smoking subgroups (Fig. 1a,b). This was consistent for both clozapine (p0.7), while non-smokers had a significantly higher C/D ratio compared to all subgroups of cigarette smokers (clozapine, p
