Tamsulosin Associated with Interstitial Lung Damage in CYP2D6 Variant Alleles Carriers

Autor: Aalt Bast, Petal A. Wijnen, Naomi T Jessurun, Otto Bekers, Eugène van Puijenbroek, Marjolein Drent
Přispěvatelé: PharmacoTherapy, -Epidemiology and -Economics, Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), MUMC+: DA CDL Analytisch cluster 1K (9), FSE Campus Venlo, RS: FSE UCV Adaptive responses in relation to health effect and safety of nutrition, RS: NUTRIM - R3 - Respiratory & Age-related Health, Farmacologie en Toxicologie, MUMC+: DA CDL (5), MUMC+: DA CDL Toegelatenen (9), Faculteit FHML Centraal
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Male
0301 basic medicine
PHARMACOGENOMICS
Cytochrome P450
Gastroenterology
TOXICITY
lcsh:Chemistry
0302 clinical medicine
Medicine
FAILURE
DRUG
lcsh:QH301-705.5
Spectroscopy
Aged
80 and over
CYP2D6
Interstitial lung disease
General Medicine
respiratory system
Computer Science Applications
Phenotype
Cytochrome P-450 CYP2D6
medicine.drug
Tamsulosin
CYP3A4/5
medicine.medical_specialty
Genotype
Single-nucleotide polymorphism
CYP2C19
Polymorphism
Single Nucleotide
behavioral disciplines and activities
Article
Catalysis
Inorganic Chemistry
03 medical and health sciences
Internal medicine
Humans
Physical and Theoretical Chemistry
CYP3A5
Molecular Biology
Alleles
Aged
business.industry
Drug-induced interstitial lung disease
Organic Chemistry
medicine.disease
Drug metabolites
respiratory tract diseases
Drug metabolizing enzymes
body regions
030104 developmental biology
030228 respiratory system
lcsh:Biology (General)
lcsh:QD1-999
Pharmacogenetics
Case-Control Studies
Pharmacogenomics
Lung Diseases
Interstitial
business
Zdroj: International Journal of Molecular Sciences, 21(8):2770. MDPI AG
International Journal of Molecular Sciences, Vol 21, Iss 2770, p 2770 (2020)
International Journal of Molecular Sciences
Volume 21
Issue 8
International journal of molecular sciences, 21(8):2770. Multidisciplinary Digital Publishing Institute (MDPI)
ISSN: 1422-0067
1661-6596
Popis: 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.
Databáze: OpenAIRE
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