Effects of CYP2D6 allelic variants on therapy with tamsulosin in patients with benign prostatic hyperplasia
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Skokhrukh P. Abdullaev
, Maksim N. Shatokhin
Abstract
Objectives
Tamsulosin is a first-line drug for the treatment of lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH). Despite its high ratings for efficacy and safety, these parameters may vary due to genetic polymorphisms of CYP2D6 enzyme, which is involved in the metabolism of the drug. This variability may have great impact on the therapy of LUTS associated with BPH and may require an individualized approach to drug selection. The aim of the study was to assess the impact of genetic polymorphisms in CYP2D6 on the efficacy and safety of tamsulosin therapy in patients with LUTS associated with BPH.
Methods
The study included 106 patients with LUTS/BPH (N40 according to ICD-10). All patients received monotherapy with tamsulosin 0.4 mg/day for at least 8 weeks. Depending on the severity of symptoms, all patients were divided into 2 groups based on the IPSS score: the first group of patients had moderate symptoms (n=57), and the second group of patients had severe symptoms (n=49). The results of treatment were assessed using the IPSS questionnaire with determination of quality of life (QoL), transrectal ultrasound of the prostate with determination of prostate volume and postvoid residual urine volume, and uroflowmetry. The carriage of allelic variants of CYP2D6 (*3, *4, *9, *10, and *41) were determined by polymerase chain reaction in all patients.
Results
In patients with moderate symptoms who was classified as «intermediate» metabolizers by CYP2D6, a statistically significant greater reduction in symptoms according to the overall IPSS scale at 8 weeks (p=0.046) and the obstructive symptom subscale starting from 4 weeks of treatment (p<0.05) was shown. Allelic variants of the CYP2D6 gene did not affect the frequency of adverse reactions to tamsulosin.
Conclusions
The results of the study show that in patients with moderate LUTS associated with BPH who are «intermediate» metabolizers by CYP2D6, there is a better therapeutic effect of tamsulosin.
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Research ethics: Research involving human subjects complied with all relevant national regulations, institutional policies and is in accordance with the tenets of the Helsinki Declaration (as revised in 2013), and has been approved by the local Ethics Committee of Russian Medical Academy of Continuous Professional Education (27th December, 2021).
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Informed consent: Informed consent was obtained from all individuals included in this study.
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Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
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Competing interests: 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 begin prostatic hyperplasia based on the use of molecular biomarkers of ADME processes”.
References
1. Lokeshwar, SD, Harper, BT, Webb, E, Jordan, A, Dykes, TA, Neal, DE, et al.. Epidemiology and treatment modalities for the management of benign prostatic hyperplasia. Transl Androl Urol 2019;8:529–39. https://doi.org/10.21037/tau.2019.10.01.Search in Google Scholar PubMed PubMed Central
2. Parsons, JK. Benign prostatic hyperplasia and male lower urinary tract symptoms: epidemiology and risk factors. Curr Bladder Dysfunct Rep 2010;5:212–8. https://doi.org/10.1007/s11884-010-0067-2.Search in Google Scholar PubMed PubMed Central
3. Cornu, JN, Gacci, M, Hashim, H, Herrmann, TR, Malde, S, Netsch, C, et al.. EAU Guidelines. Edn. presented at the EAU Annual Congress Milan 2023 Arnhem, The Netherlands: EAU Guidelines Office. ISBN 978-94-92671-19-6.Search in Google Scholar
4. Michel, MC, Kenny, B, Schwinn, DA. Classification of alpha 1-adrenoceptor subtypes. Naunyn-Schmiedeb Arch Pharmacol 1995;352:1–10. https://doi.org/10.1007/bf00169183.Search in Google Scholar
5. Rasner, PI, Pushkar, DI. Lechenie simptomov nizhnikh mochevykh putei u patsientov s dobrokachestvennoi giperplaziei predstatel’noi zhelezy: sovremennye mezhdunarodnye standarty. Sprav Poliklin Vracha 2015;10:20–6.Search in Google Scholar
6. Roehrborn, CG. Efficacy of alpha-adrenergic receptor blockers in the treatment of male lower urinary tract symptoms. Rev Urol 2009;11:S1–8.Search in Google Scholar
7. Kim, KA, Park, IB, Park, JY. Effects of CYP2D6 and CYP3A5 genetic polymorphisms on steady-state pharmacokinetics and hemodynamic effects of tamsulosin in humans. Eur J Clin Pharmacol 2018;74:1281–9. https://doi.org/10.1007/s00228-018-2501-x.Search in Google Scholar PubMed
8. Choi, CI, Bae, JW, Jang, CG, Lee, SY. Tamsulosin exposure is significantly increased by the CYP2D6*10/*10 genotype. J Clin Pharmacol 2012;52:1934–8. https://doi.org/10.1177/0091270011432168.Search in Google Scholar PubMed
9. Villapalos-García, G, Zubiaur, P, Navares-Gómez, M, Saiz-Rodriguez, M, Mejia-Abril, G, Martin-Vilchez, S, et al.. Effects of cytochrome P450 and transporter polymorphisms on the bioavailability and safety of dutasteride and tamsulosin. Front Pharmacol 2021;12:718281. https://doi.org/10.3389/fphar.2021.718281.Search in Google Scholar PubMed PubMed Central
10. Taylor, C, Crosby, I, Yip, V, Maguire, P, Pirmohamed, M, Turner, RM. A Review of the important role of CYP2D6 in pharmacogenomics. Genes 2020;11:1295. https://doi.org/10.3390/genes11111295.Search in Google Scholar PubMed PubMed Central
11. Gaedigk, A. Complexities of CYP2D6 gene analysis and interpretation. Int Rev Psychiatr 2013;25:534–53. https://doi.org/10.3109/09540261.2013.825581.Search in Google Scholar PubMed
12. Elens, L, van Gelder, T, Hesselink, DA, Haufroid, V, van Schaik, RH. CYP3A4*22: promising newly identified CYP3A4 variant allele for personalizing pharmacotherapy. Pharmacogenomics 2013;14:47–62. https://doi.org/10.2217/pgs.12.187.Search in Google Scholar PubMed
13. Caudle, KE, Sangkuhl, K, Whirl-Carrillo, M, Swen, JJ, Haidar, CE, Klein, TE, et al.. Standardizing CYP2D6 genotype to phenotype translation: consensus recommendations from the clinical pharmacogenetics implementation consortium and Dutch pharmacogenetics working group. Clin Transl Sci 2020;13:116–24. https://doi.org/10.1111/cts.12692.Search in Google Scholar PubMed PubMed Central
14. Pushkar, DY, Rasner, PI, Kharchilava, RR. Lower urinary tract symptoms and benign prostatic hyperplasia. Urologiia 2016;2:4–19. https://doi.org/10.18565/urol.2017.3-supplement.4-18.Search in Google Scholar
15. Brockmöller, J, Tzvetkov, MV. Pharmacogenetics: data, concepts and tools to improve drug discovery and drug treatment. Eur J Clin Pharmacol 2008;64:133–57. https://doi.org/10.1007/s00228-007-0424-z.Search in Google Scholar PubMed PubMed Central
16. Mini, E, Nobili, S. Pharmacogenetics: implementing personalized medicine. Clin Cases Miner Bone Metab 2009;6:17–24.Search in Google Scholar
17. Samani, NJ, Tomaszewski, M, Schunkert, H. The personal genome-the future of personalised medicine? Lancet 2010;375:1497–8. https://doi.org/10.1016/s0140-6736(10)60598-3.Search in Google Scholar
18. Collins, FS, Varmus, H. A new initiative on precision medicine. N Engl J Med 2015;372:793–5. https://doi.org/10.1056/nejmp1500523.Search in Google Scholar
19. Zanger, UM, Schwab, M. Cytochrome P450 enzymes in drug metabolism: regulation of gene expression, enzyme activities, and impact of genetic variation. Pharmacol Ther 2013;138:103–41. https://doi.org/10.1016/j.pharmthera.2012.12.007.Search in Google Scholar PubMed
20. CYP2D6 CPIC, guidelines. [Internet]. Stanford University & St. Jude Children’s Research Hospital. Available from: https://cpicpgx.org/gene/cyp2d6/.Search in Google Scholar
21. Boehringer Ingelheim GmbH Flomax (tamsulosin hydrochloride). Highlights of prescribing information. 2016. http://bidocs.boehringer-ingelheim.com/BIWebAccess/ViewServlet.ser?docBase=renetnt&folderPath=/Prescribing+Information/PIs/Flomax+Caps/Flomax.pdf [Assessed 22 May 2018].Search in Google Scholar
22. Troost, J, Tatami, S, Tsuda, Y, Mattheus, M, Mehlburger, L, Wein, M, et al.. Effects of strong CYP2D6 and 3A4 inhibitors, paroxetine and ketoconazole, on the pharmacokinetics and cardiovascular safety of tamsulosin. Br J Clin Pharmacol 2011;72:247–56. https://doi.org/10.1111/j.1365-2125.2011.03988.x.Search in Google Scholar PubMed PubMed Central
23. Roehrborn, CG, Schwinn, DA. Alpha1-adrenergic receptors and their inhibitors in lower urinary tract symptoms and benign prostatic hyperplasia. J Urol 2004;171:1029–35. https://doi.org/10.1097/01.ju.0000097026.43866.cc.Search in Google Scholar PubMed
24. Wilt, TJ, Howe, W, MacDonald, R. Terazosin for treating symptomatic benign prostatic obstruction: a systematic review of efficacy and adverse effects. BJU Int 2002;89:214–25. https://doi.org/10.1046/j.1464-4096.2001.02537.x-i1.Search in Google Scholar
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Articles in the same Issue
- Frontmatter
- Editorial
- Ancestromics
- Reviews
- PDE5 inhibitors: breaking new grounds in the treatment of COVID-19
- Phytochemical profiling and biological activities of Diplazium esculentum (Retz.) Sw.: an edible vegetable fern
- Original Articles
- Effects of CYP2D6 allelic variants on therapy with tamsulosin in patients with benign prostatic hyperplasia
- CRHR1 polymorphism at rs242941, rs242940, and rs72834580: association of symptoms improvement with intranasal corticosteroids in allergic rhinitis Jordanian patients
- Predictive modeling of adverse drug reactions to tamoxifen therapy for breast cancer on base of pharmacogenomic testing
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- Multifunctional analysis and antimicrobial activity of Adhatoda vasica: a traditional medicinal plant
- Letter to the Editor
- Kamini Vidrawan Ras inducing opioid dependence? – understanding the facts