Tamsulosin Associated with Interstitial Lung Damage in CYP2D6 Variant Alleles Carriers

Naomi T. Jessurun*, Petal A. Wijnen, Aalt Bast, Eugene P. van Puijenbroek, Otto Bekers, Marjolein Drent

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

2 Citations (Web of Science)

Abstract

Drugs are serious but underestimated causative agents of interstitial lung disease (ILD). Both cytotoxic and immune mechanisms may be involved in drug-induced ILD (DI-ILD). We aimed to investigate whether polymorphisms of relevant CYP enzymes involved in the metabolization of tamsulosin might explain the pathologic mechanism of the DI-ILD in the cases with suspected tamsulosin DI-ILD. We collected 22 tamsulosin-associated DI-ILD cases at two ILD Expertise Centers in the Netherlands between 2009 and 2020. CYP2D6, CYP2C9, CYP2C19, CYP3A4, and CYP3A5 single nucleotide polymorphisms were genotyped and compared with a control group of 78 healthy Caucasian male volunteers. Nine cases were phenotyped as CYP2D6 poor metabolizers and 13 as CYP2D6 intermediate metabolizers. The phenotypes of the cases differed significantly from those of the healthy controls, with more poor metabolizers. After withdrawal of tamsulosin, the pulmonary condition of three cases had improved, six patients had stabilized, and one patient stabilized after reducing the tamsulosin dose. The described 22 cases suggest that an association between the presence of CYP2D6 allelic variants and tamsulosin-associated ILD is highly likely. These cases highlight the importance of both clinical and genetic risk stratification aimed to achieve a more accurate prevention of DI-ILD in the future and enhance the quality of life of patients.

Original languageEnglish
Article number2770
Number of pages9
JournalInternational journal of molecular sciences
Volume21
Issue number8
DOIs
Publication statusPublished - Apr 2020

Keywords

  • tamsulosin
  • drug-induced interstitial lung disease
  • pharmacogenetics
  • CYP2D6
  • CYP3A4/5
  • drug metabolizing enzymes
  • drug metabolites
  • cytochrome P450
  • DRUG
  • PHARMACOGENOMICS
  • TOXICITY
  • FAILURE

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