CYP2D6 genetic polymorphisms impact on tamsulosin efficacy and safety in patients with benign prostatic hyperplasia
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Shokhrukh Abdullaev
,
Maksim Shatokhin
,
Ivan Sychev
,
Aleksandr Krasnov
,
Pavel Bochkov
,
Svetlana Tuchkova
,
Oleg Teodorovich
,
Oleg Loran
,
Sherzod Abdullaev
and
Dmitry Sychev
Abstract
Objectives
The clinical outcomes of tamsulosin therapy for LUTS/BPH patients vary, with up to one-third of patients reporting unsatisfactory results. Enhancing the effectiveness and safety of tamsulosin therapy for LUTS/BPH patients remains a significant challenge in current medical practice. Limited data exists regarding the impact of CYP2D6 genetic polymorphisms on the efficacy and safety of tamsulosin therapy. Given that tamsulosin is metabolized by CYP2D6, variations in this enzyme may influence the drug's pharmacodynamic response. The objective of this study was to evaluate the impact of CYP2D6 pharmacogenetic markers on tamsulosin efficacy and safety in patients with LUTS associated with BPH.
Methods
The study included 142 male patients with LUTS and a confirmed diagnosis of BPH (N40 ICD-10). Patients were followed for a minimum of 8 weeks and underwent four examinations (at days 0, 14, 28, and 56). Treatment efficacy was assessed using the IPSS with quality of life assessment, transrectal ultrasound of the prostate with estimation of prostate volume and residual urine volume, and maximum urinary flow rate (Qmax). Allelic variants of CYP2D6 (*2, *3, *4, *6, *9, *10, and *41) were determined by polymerase chain reaction in all patients..
Results
In the subgroup with moderate symptoms, individuals classified as poor and intermediate metabolizers exhibited significantly higher ΔQmax compared to normal metabolizers (4.25 [2.5; 6.1] vs. [0.6; 4.3], p=0.001826). Moreover, carriers of the CYP2D6*10 CT heterozygous genotype demonstrated lower IPSS scores at the last two visits compared to those with the CC genotype (visit 3: −7.45 ± 3.93 vs. −5.25 ± p=0.05; visit 4: −8.91 ± 3.88 vs. −6.31 ± 5.7), as well as reduced IPSS irritative symptoms at visit 2 (−3.87 ± 2.70 vs −2.47 ± 3.1, p=0.05), and a significant increase in ΔQmax ([2.5; 5.9] vs. [0.6; 4.7], p=0.01). In the subgroup with severe symptoms, individuals with CYP2D6*41 GA + AA genotypes exhibited less residual urine volume following therapy compared to those with the GG genotype ([15.0; 32.0] vs. [3.0; 19.0], p=0.007029). The CYP2D6 polymorphic variants did not impact the tamsulosin safety. The study did not reach the estimated power for CYP2D6*3, CYP2D6*6, and CYP2D6*9 polymorphisms due to their low frequency of occurrence in the study population. The multivariate logistic regression model indicated that potential predictors of tamsulosin therapy efficacy in LUTS/BPH patients may include BMI (p<0.001), prostate volume (p<0.002), as well as the carriage of CYP2D6*4 (p<0.001) and CYP2D6*10 (p=0.012) markers. The model explained 81.9 % of the variance in the predicted outcome and accurately forecasted tamsulosin therapy efficacy in BPH with a precision of 92.1 %.
Conclusions
The present study identified potential markers that could serve as predictors of the effectiveness of tamsulosin. Specifically, genetic markers such as CYP2D6*4, CYP2D6*10, CYP2D6*41, and non-genetic factors like BMI and prostate volume were associated with the clinical efficacy of tamsulosin therapy in LUTS/BPH patients..
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Research ethics: The study was approved by the Ethics Committee of Scientific Research of Russian Medical Academy of Continuous Professional Education (Protocol No. 13 dated 27 Dec 2021) and conducted in accordance with the Helsinki Declaration (as revised in 2013).
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Informed consent: Informed consent was obtained from all individuals included in this study, or their legal guardians or wards.
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Author contributions: The authors have accepted responsibility for the entire content of this manuscript and approved its submission.
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Use of Large Language Models, AI and Machine Learning Tools: None declared.
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Conflict of interest: The authors state no conflict of interest.
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Research funding: This work was supported by the Russian Science Foundation under Grant No. 23-15-00310 “Personalized pharmacotherapy for patients with benign prostatic hyperplasia based on the use of molecular biomarkers of ADME processes”.
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Data availability: The raw data can be obtained on request from the corresponding author.
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Articles in the same Issue
- Frontmatter
- Review
- Unlocking the therapeutic potential and personalized therapy of testosterone: a comprehensive review
- Original Articles
- Prolonged post-operative hydrocodone usage due to psychotropic drug interaction
- An open-label, single dose, safety and pharmacokinetic study of Withania somnifera root extract in healthy volunteers
- Effect of metformin on exercise capacity in treatment naïve type 2 diabetes patients
- Molecular docking and in vitro evaluation of glucosamine sulfate targeting MMP-3, MMP-9, and IL-4 for potential osteoarthritis treatment
- CYP2D6 genetic polymorphisms impact on tamsulosin efficacy and safety in patients with benign prostatic hyperplasia
- Predicting of factors associated with valsartan response among hypertensive patients attending the Jordan University Hospital
