Differences in the pharmacokinetics of psychopharmacological drugs between smokers and nonsmokers

 

Introduction:

Smoking behavior is an underestimated pharmacokinetic parameter in pharmacological treatment. Even if the pharmacokinetic induction of smoking on CYP1A2 has been described repeatedly, some studies discuss an influence of smoking via other CYP isoenzymes, also. Due to unequivocal results further analyses are necessary to assess the influence factor smoking on serum concentration of antidepressant and antipsychotic drugs.

Methods:

Therapeutic Drug Monitoring (TDM) data from 2009 to 2010 of the antidepressants amitriptyline (n = 503), doxepin (n = 198), escitalopram (n = 199), mirtazapine (n = 572) venlafaxine (n = 534) and the antipsychotics clozapine (n = 106), quetiapine (n = 182) and risperidone (n = 136) were retrospectively statistically analysed. A linear regression analysis regarding the influence of age, sex and smoking habits of the patients on the dose-corrected serum levels (C/D) of the drugs was realized.

Results:

A significant influence of smoking on the C/D of amitriptyline, clozapine, escitalopram and mirtazapine was found. C/D of mirtazapine and amitriptyline were additionally significantly influenced by age and sex and C/D of escitalopram by age. The ratio nortriptyline/amitriptyline was significantly influenced by smoking behaviour and the ratio nordoxepin/doxepin by smoking and age.

Discussion:

Smoking alters the pharmacokinetics of psychopharmacological drugs not only via induction of CYP1A2, but possibly also via CYP2C19 and CYP3A4. In contrast to most previous studies, in which the confounding of smoking behaviour by age and sex was ignored, the present study considered these variables and included a higher number of patients.