[The influence of clomipramine on CYP2D6 activity].
OBJECTIVE
Genetically determined activity ofCYP2D6 may be modified by some drugs through inhibition processes. Inhibition properties of TCA's were confirmed mainly in in vitro studies. The aim of the study was to assess the influence of clomipramine on CYP2D6 activity in vivo.


METHODS
11 patients diagnosed with depression according to ICD-10 and DSM-IV (major depression) criteria were included in the study. In all the cases clomipramine therapy was indicated. CYP2D6 activity was assessed by the phenotyping method. All patients were treated simultaneously. Each of the patients ingested one tablet containing 100 mg of sparteine sulfate. Urine excreted during the following 6 h was collected. Based on sparteine metabolic ratio (MR) the phenotype status was estimated twice: after the wash-out period, before clomipramine treatment, sparteine metabolic ratio (MRI), and after 2-weeks of clomipramine treatment (MR2).


RESULTS
During clomipramine treatment MR2 values were statistically significantly higher than MRI. In 3 patients (27.3%) treated with clomipramine the changes of phenotype status were observed.


CONCLUSIONS
Clomipramine is a CYP2D6 inhibitor and may change the CYP2D6 phenotype status (EM into PM).
Szewczuk-Bogusławska
Monika
M
Katedra i Klinika Psychiatrii AM we Wrocławiu.
Kiejna
Andrzej
A
Grzesiak
Magdalena
M
Beszłej
Jan Aleksander
JA
Chlebowska
Iwona
I
Orzechowska-Juzwenko
Krystyna
K
Milejski
Piotr
P
D000328:Adult; D000368:Aged; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology* / Q000627:therapeutic use; D002997:Clomipramine / Q000494:pharmacology* / Q000627:therapeutic use; D019389:Cytochrome P-450 CYP2D6 / Q000187:drug effects* / Q000378:metabolism; D003863:Depression / Q000188:drug therapy* / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged
D000929:Antidepressive Agents, Tricyclic; D019389:Cytochrome P-450 CYP2D6; D002997:Clomipramine