Impact of CYP2D6 polymorphisms on the pharmacokinetics, efficacy, and safety of tamsulosin therapy in patients with benign prostatic hyperplasia
Abstract
Introduction. CYP2D6 is involved in the metabolism of tamsulosin, which is used to treat lower urinary tract symptoms (LUTS) in benign prostatic hyperplasia (BPH). However, the impact of carrying polymorphic variants of the CYP2D6 gene on the clinical efficacy and safety of tamsulosin therapy is still not well understood.Aim. To evaluate the impact of CYP2D6 polymorphic variants on steady state concentration of tamsulosin (Cssmin), as well as their correlation with the efficacy and safety of therapy in patients with BPH.Materials and methods. A single-center prospective study included 75 patients who completed all stages of the study. The median age of the patients was 69 years, body mass index was 27.17 ± 4.86 kg/m². 56 patients (74.67%) had comorbidities, which means the presence of at least one chronic disease in addition to the diagnosis of benign prostatic hyperplasia. 26 people (34.67%) were classified as polymorbid patients, i.e. having several comorbidities at once, while 19 patients (25.33%) had no comorbidities except for benign prostatic hyperplasia. Genotyping was performed by real-time polymerase chain reaction. Cssmin of tamsulosin was determined by HPLC-MS/MS. Efficacy of therapy was assessed using IPSS score and Qmax. Safety was assessed based on the incidence of adverse reactions.Results. Carriage of CYP2D6*4 and CYP2D6*10 was found to be associated with statistically significant increases in Cssmin levels. However, the identified pharmacokinetic…
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