Effect of smoking and CYP2D6 polymorphisms on the extent of fluvoxamine-alprazolam interaction in patients with psychosomatic disease

Hideyo Sugahara, Chiharu Maebara, Hisakazu Ohtani, Masanori Handa, Katsumi Ando, Kazunori Mine, Chiharu Kubo, Ichiro Ieiri, Yasufumi Sawada

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Purpose: Fluvoxamine (FVX) is metabolized by cytochrome P450 (CYP) 2D6 and CYP1A2 and inhibits CYP3A4. The aim of this study was to investigate the factors responsible for interindividual variability in the extent of interaction between FVX and alprazolam (ALP). Methods: Blood samples were taken from 49 depressive patients to determine plasma concentration of FVX, ALP or both. Twenty-four samples were taken during the FVX-alone period, 21 samples during the ALP-alone period and 30 samples during the FVX-ALP period. Subjects were also genotyped for CYP2D6. Results: The concentration-to-dose (C/D) ratio of ALP during the FVX-treatment period was significantly higher than that during the ALP-alone period. The CYP2D6 genotype affected neither the C/D ratios of FVX nor the extent of interaction. The mean C/D ratio of FVX in smokers was reduced by more than 30% in comparison with that in non-smokers. The mean C/D ratio of ALP in non-smokers was increased by FVX, while that in smokers was unchanged. Conclusions: The extent of interaction between FVX and ALP may be affected by smoking, which alters the C/D ratio of FVX. Therefore, when FVX and ALP are concomitantly administered, it should be noted that non-smokers may exhibit greater drug interaction than smokers.

Original languageEnglish
Pages (from-to)699-704
Number of pages6
JournalEuropean Journal of Clinical Pharmacology
Volume65
Issue number7
DOIs
Publication statusPublished - 2009 Jul
Externally publishedYes

Fingerprint

Alprazolam
Fluvoxamine
Cytochrome P-450 CYP2D6
Smoking
Cytochrome P-450 CYP3A
Cytochrome P-450 CYP1A2
Drug Interactions

Keywords

  • Alprazolam
  • CYP2D6
  • Drug interaction
  • Fluvoxamine
  • Polymorphism
  • Smoking

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology

Cite this

Effect of smoking and CYP2D6 polymorphisms on the extent of fluvoxamine-alprazolam interaction in patients with psychosomatic disease. / Sugahara, Hideyo; Maebara, Chiharu; Ohtani, Hisakazu; Handa, Masanori; Ando, Katsumi; Mine, Kazunori; Kubo, Chiharu; Ieiri, Ichiro; Sawada, Yasufumi.

In: European Journal of Clinical Pharmacology, Vol. 65, No. 7, 07.2009, p. 699-704.

Research output: Contribution to journalArticle

Sugahara, Hideyo ; Maebara, Chiharu ; Ohtani, Hisakazu ; Handa, Masanori ; Ando, Katsumi ; Mine, Kazunori ; Kubo, Chiharu ; Ieiri, Ichiro ; Sawada, Yasufumi. / Effect of smoking and CYP2D6 polymorphisms on the extent of fluvoxamine-alprazolam interaction in patients with psychosomatic disease. In: European Journal of Clinical Pharmacology. 2009 ; Vol. 65, No. 7. pp. 699-704.
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T1 - Effect of smoking and CYP2D6 polymorphisms on the extent of fluvoxamine-alprazolam interaction in patients with psychosomatic disease

AU - Sugahara, Hideyo

AU - Maebara, Chiharu

AU - Ohtani, Hisakazu

AU - Handa, Masanori

AU - Ando, Katsumi

AU - Mine, Kazunori

AU - Kubo, Chiharu

AU - Ieiri, Ichiro

AU - Sawada, Yasufumi

PY - 2009/7

Y1 - 2009/7

N2 - Purpose: Fluvoxamine (FVX) is metabolized by cytochrome P450 (CYP) 2D6 and CYP1A2 and inhibits CYP3A4. The aim of this study was to investigate the factors responsible for interindividual variability in the extent of interaction between FVX and alprazolam (ALP). Methods: Blood samples were taken from 49 depressive patients to determine plasma concentration of FVX, ALP or both. Twenty-four samples were taken during the FVX-alone period, 21 samples during the ALP-alone period and 30 samples during the FVX-ALP period. Subjects were also genotyped for CYP2D6. Results: The concentration-to-dose (C/D) ratio of ALP during the FVX-treatment period was significantly higher than that during the ALP-alone period. The CYP2D6 genotype affected neither the C/D ratios of FVX nor the extent of interaction. The mean C/D ratio of FVX in smokers was reduced by more than 30% in comparison with that in non-smokers. The mean C/D ratio of ALP in non-smokers was increased by FVX, while that in smokers was unchanged. Conclusions: The extent of interaction between FVX and ALP may be affected by smoking, which alters the C/D ratio of FVX. Therefore, when FVX and ALP are concomitantly administered, it should be noted that non-smokers may exhibit greater drug interaction than smokers.

AB - Purpose: Fluvoxamine (FVX) is metabolized by cytochrome P450 (CYP) 2D6 and CYP1A2 and inhibits CYP3A4. The aim of this study was to investigate the factors responsible for interindividual variability in the extent of interaction between FVX and alprazolam (ALP). Methods: Blood samples were taken from 49 depressive patients to determine plasma concentration of FVX, ALP or both. Twenty-four samples were taken during the FVX-alone period, 21 samples during the ALP-alone period and 30 samples during the FVX-ALP period. Subjects were also genotyped for CYP2D6. Results: The concentration-to-dose (C/D) ratio of ALP during the FVX-treatment period was significantly higher than that during the ALP-alone period. The CYP2D6 genotype affected neither the C/D ratios of FVX nor the extent of interaction. The mean C/D ratio of FVX in smokers was reduced by more than 30% in comparison with that in non-smokers. The mean C/D ratio of ALP in non-smokers was increased by FVX, while that in smokers was unchanged. Conclusions: The extent of interaction between FVX and ALP may be affected by smoking, which alters the C/D ratio of FVX. Therefore, when FVX and ALP are concomitantly administered, it should be noted that non-smokers may exhibit greater drug interaction than smokers.

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