Effects of CYP2D6 allelic variants on therapy with tamsulosin in patients with benign prostatic hyperplasia
Skokhrukh P. Abdullaev, Maksim N. Shatokhin, Svetlana N. Tuchkova, Sherzod P. Abdullaev, Oleg V. Teodorovich, Oleg B. Loran, Dmitry A. Sychev- Pharmacology (medical)
- General Pharmacology, Toxicology and Pharmaceutics
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.