Association of CYP3A4*1B, CYP3A4*22 and CYP3A5*3 polymorphisms carriage with efficacy and safety of tamsulosin in patients with benign prostatic hyperplasia

Author:

Abdullaev Sh. P.1ORCID,Shatokhin M. N.2ORCID,Sigailo O. L.3ORCID,Abdullaev Sh. P.3ORCID,Bochkov P. O.3ORCID,Tuchkova S. N.3ORCID,Teodorovich O. V.2ORCID,Loran O. B.3ORCID,Sychev D. A.4ORCID

Affiliation:

1. 1. Russian Medical Academy of Continuous Professional Education (RMACPE). 2. Kurchatov Institute.

2. 1. Russian Medical Academy of Continuous Professional Education (RMACPE). 2. Central Hospital «Russian Railways-Medicine».

3. Russian Medical Academy of Continuous Professional Education (RMACPE)

4. Russian Medical Academy of Continuous Professional Education (RMACPE).

Abstract

Tamsulosin is a first-line drug in the treatment of lower urinary tract symptoms (LUTS) in benign prostatic hyperplasia (BPH). Despite high estimates of its efficacy and safety, it rates may vary due to genetic polymorphisms of genes for the enzymes involved in the drugs metabolism.The aim of the work was to evaluate the carriage influence of genes polymorphisms of the CYP3A enzymes group of tamsulosin metabolizers on the efficacy and safety of therapy in patients with LUTS in BPH.Materials and methods. A total of 142 patients with LUTS, with an established BPH diagnosis (N40 according to ICD-10) were included in the study and underwent all stages. All patients received monotherapy with tamsulosin 0.4 mg/day for at least 8 weeks. An IPSS questionnaire with the definition of quality of life, a prostate ultrasound with the determination of the prostate volume and residual urine, as well as uroflowmetry, were used to evaluate the results of the treatment. Controls were performed at 2, 4 and 8 weeks from the start of the therapy. The carriage of polymorphic markers CYP3A4 (*1B, *22) and CYP3A5*3 was determined in patients; HPLC was used to determine drug concentrations in blood plasma and levels of cortisol and its metabolite 6-beta-hydroxycortisol in urine to assess the phenotypic activity of CYP3A.Results. No statistically significant associations between CYP3A phenotype (defined by CYP3A4 and CYP3A5 genotypes) and clinical parameters of the tamsulosin therapy efficacy and the safety assessment in the studied sample of patients were found (p >0.05). Similar data were obtained for individual variants of CYP3A4*1B, CYP3A4*22, CYP3A5*3 (p >0.05). The comparison of the tamsulosin residual equilibrium concentration values in patients in the study sample with respect to the carriers of CYP3A4 and CYP3A5 gene variants did not reveal the presence of significant differences in either CYP3A phenotypes  and carriers and non-carriers of individual CYP3A4*1B (p=0.57), CYP3A4*22 (p=0.37) and CYP3A5*3 (p=0.76) variants. No association was found between the metabolic ratio of 6-beta-hydroxycortisol / cortisol in urine and the CYP3A phenotype encoded by a combination of genotypes of CYP3A4 and CYP3A5 gene variants (p >0.05).Conclusion. A possible association between the carriage of CYP3A4*1B, CYP3A4*22, CYP3A5*3 variants, a CYP3A activity assessed by the content of an endogenous substrate of this isoenzyme and its metabolite in urine, the level of plasma concentration of the drug, and the efficacy and safety of tamsulosin, has not been confirmed. The contribution of CYP3A4 and CYP3A5 genetic polymorphisms to clinical parameters of the tamsulosin therapy requires a further study.

Publisher

Volgograd State Medical University

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3