The effect of variable cigarette consumption on the interaction with clozapine and olanzapine.
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).


CONCLUSIONS
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.
Haslemo
Tore
T
Department of Psychopharmacology, Diakonhjemmet Hospital, Postbox 85, Vinderen, Oslo 0319, Norway. tore.haslemo@diakonsyk.no
Eikeseth
Per Haakon
PH
Tanum
Lars
L
Molden
Espen
E
Refsum
Helge
H
D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D001569:Benzodiazepines / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002851:Chromatography, High Pressure Liquid; D003024:Clozapine / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D006801:Humans; D007297:Inpatients / Q000706:statistics & numerical data; D008297:Male; D013058:Mass Spectrometry; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009735:Nursing Homes; D000077152:Olanzapine; D012559:Schizophrenia / Q000188:drug therapy / Q000378:metabolism; D012907:Smoking / Q000097:blood*
D014150:Antipsychotic Agents; D001569:Benzodiazepines; D019388:Cytochrome P-450 CYP1A2; D003024:Clozapine; D000077152:Olanzapine