-
Frontiers in Pharmacology 2021Dutasteride and tamsulosin are one of the first-line combination therapies for the management of benign prostatic hyperplasia (BPH). Despite being more effective than...
Dutasteride and tamsulosin are one of the first-line combination therapies for the management of benign prostatic hyperplasia (BPH). Despite being more effective than monotherapies, they produce frequent adverse drug reactions (ADRs). Institutions such as Food and Drug Administration and European Medicines Agency recommend precaution with poor metabolizers (PMs) that receive inhibitors and tamsulosin. However, no specific pharmacogenetic guideline exists for tamsulosin. Furthermore, to date, no pharmacogenetic information is available for dutasteride. Henceforth, we studied the pharmacokinetics and safety of dutasteride/tamsulosin 0.5 mg/0.4 mg capsules according to 76 polymorphisms in 17 candidate pharmacogenes. The study population comprised 79 healthy male volunteers enrolled in three bioequivalence, phase-I, crossover, open, randomized clinical trials with different study designs: the first was single dose in fed state, the second was a single dose in fasting state, and the third was a multiple dose. As key findings, PMs (i.e., *4/*4 and *4/*5 subjects) and intermediate metabolizers (IMs) (i.e., *1/*4, *1/*5, *4/*15 individuals) presented higher AUC ( = 0.004), higher t ( = 0.008), and lower Cl/F ( = 0.006) when compared with NMs (*1/*1 individuals) and UMs (1/*1 × 2 individuals) after multiple testing correction. Moreover, fed volunteers showed significantly higher t than fasting individuals. Nominally significant associations were observed between dutasteride exposure and and genotype and between tamsulosin and , , and genotypes. No association between the occurrence of adverse drug reactions and genotype was observed. Nonetheless, higher incidence of adverse events was found in a multiple-dose clinical trial. Based on our results, we suggest that dose adjustments for PMs and UMs could be considered to ensure drug safety and effectiveness, respectively. Further studies are warranted to confirm other pharmacogenetic associations.
PubMed: 34690761
DOI: 10.3389/fphar.2021.718281 -
Medicine Mar 2016Acupuncture is a promising therapy for relieving symptoms in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), which affects >15% of adult men worldwide. The... (Review)
Review
Acupuncture is a promising therapy for relieving symptoms in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), which affects >15% of adult men worldwide. The aim of the study was to assess the effects and safety of the use of acupuncture for CP/CPPS. MEDLINE, EMBASE, CENTRAL, Web of Science, CBM, CNKI, Wang-Fang Database, JCRM, and CiNii were searched from their inception through 30 November 2015. Grey literature databases and websites were also searched. No language limits were applied. Only randomized controlled trials (RCTs) with CP/CPPS treated by acupuncture were included. Two reviewers extracted data and assessed the risk of bias of RCTs using the Cochrane Risk of Bias Tools, respectively. Seven trials were included, involving 471 participants. The result of meta-analysis indicated that compared with sham acupuncture (MD: -6.09 [95%CI: -8.12 to -5.68]) and medicine (Levofloxacinand, Ibuprofen, and Tamsulosin) (MD: -4.57 [95%CI: -7.58 to -1.56]), acupuncture was more effective at decreasing the total NIH-CPSI score. Real acupuncture was superior to sham acupuncture in improving symptoms (pain, voiding) and quality of life (Qof) domain subscores. Compared to sham acupuncture and medicine, acupuncture appears to be more effective at improving the global assessment. Two trials found that there is no significant difference between acupuncture and sham acupuncture in decreasing the IPSS score. Acupuncture failed to show more favorable effects in improving both symptoms and the Qof domain compared with medicine. Overall, current evidence supports acupuncture as an effective treatment for CP/CPPS-induced symptoms, particularly in relieving pain. Based on the meta-analysis, acupuncture is superior to sham acupuncture in improving symptoms and Qof. Acupuncture might be similar to medicine (Levofloxacinand, Ibuprofen, and Tamsulosin) in its long-term effects, but evidence was limited due to high ROB among included trials as well as potential heterogeneity. Acupuncture is associated with rare and slightly adverse events. Protocol registration PROSPERO CRD42015027522.
Topics: Acupuncture Therapy; Chronic Disease; Humans; Male; Pelvic Pain; Prostatitis
PubMed: 26986148
DOI: 10.1097/MD.0000000000003095 -
Singapore Medical Journal Jun 2018
Topics: Adrenergic alpha-1 Receptor Antagonists; Aged; Betamethasone; Betamethasone Valerate; Clobetasol; Exanthema; Hernia, Inguinal; Humans; Light; Male; Myocardial Ischemia; Ointments; Peptic Ulcer; Photosensitivity Disorders; Prostatic Hyperplasia; Pulmonary Disease, Chronic Obstructive; Steroids; Sulfonamides; Tamsulosin; Tuberculosis, Pulmonary
PubMed: 29974124
DOI: 10.11622/smedj.2018072 -
Surgery Nov 2018Tamsulosin, an α-adrenergic receptor inhibitor, is prescribed to treat benign prostatic hyperplasia in men >60 years of age, the same demographic most susceptible to...
BACKGROUND
Tamsulosin, an α-adrenergic receptor inhibitor, is prescribed to treat benign prostatic hyperplasia in men >60 years of age, the same demographic most susceptible to abdominal aortic aneurysm. The goal of this study was to investigate the effect of tamsulosin on abdominal aortic aneurysm pathogenesis.
METHODS
Abdominal aortic aneurysms were induced in WT C57BL/6 male mice (n = 9-18/group), using an established topical elastase abdominal aortic aneurysm model. Osmotic pumps were implanted in mice 5 days before operation to create the model, administering either low dose (0.125 µg/day tamsulosin), high dose (0.250µg/day tamsulosin), or vehicle treatments with and without topical application of elastase. Blood pressures were measured preoperatively and on postoperative days 0, 3, 7, and 14. On postoperative day 14, aortic diameter was measured before harvest. Sample aortas were prepared for histology and cytokine analysis.
RESULTS
Measurements of systolic blood pressure did not differ between groups. Mice treated with the low dose of tamsulosin and with the high dose of tamsulosin showed decreased aortic diameter compared with vehicle-treated control (93% ± 24 versus 94% ± 30 versus 132% ± 24, respectively; P = .0003, P = .0003). Cytokine analysis demonstrated downregulation of pro-inflammatory cytokines in both treatment groups compared with the control (P < .05). Histology exhibited preservation of elastin in both low- and high-dose tamsulosin-treated groups (P = .0041 and P = .0018, respectively).
CONCLUSION
Tamsulosin attenuates abdominal aortic aneurysm formation with increased preservation of elastin and decreased production of pro-inflammatory cytokines. Further studies are necessary to elucidate the mechanism by which tamsulosin attenuates abdominal aortic aneurysm pathogenesis.
Topics: Adrenergic alpha-1 Receptor Antagonists; Animals; Aorta, Abdominal; Aortic Aneurysm, Abdominal; Blood Pressure; Cytokines; Disease Models, Animal; Down-Regulation; Drug Evaluation, Preclinical; Elastin; Humans; Male; Mice; Mice, Inbred C57BL; Pancreatic Elastase; Tamsulosin; Treatment Outcome
PubMed: 30174141
DOI: 10.1016/j.surg.2018.06.036 -
Anatomical Record (Hoboken, N.J. : 2007) Feb 2023Ductus arteriosus is a muscular artery in fetal circulation, spanning from the bifurcation of the pulmonary trunk to the aortic arch, shunting blood directly from...
Ductus arteriosus is a muscular artery in fetal circulation, spanning from the bifurcation of the pulmonary trunk to the aortic arch, shunting blood directly from pulmonary circulation into systemic circulation thus by-passing the fluid-filled lungs. Postnatally, it changes name to the ligamentum arteriosum (LA), when a cascade of anatomical and physiological processes leads to its closure. Though the LA has generally been considered as a fibrosed remnant of the ductus arteriosus, anecdotal and contradictory reports still describe the LA as a small muscular artery. We hypothesized the likelihood of contractile muscular elements retainment in this so-called ligament. To investigate this, mediastinum of wild-type mouse, pig, and human LA were subjected to routine and special histological staining, single-immunolabeling, electron microscopy (mouse and pig only), and tension recording of explanted pig LA in organ bath experiments. Contrary to a canonical ligament, the LA was mainly made up of α-smooth muscle actin-positive cells in all three species, confirmed by routine and special histological staining as well as transmission electron microscopy. Myocytes within the LA contracted in response to exogenous noradrenalin (NA). NA-induced precontracted LA relaxed upon administration of the α1-adrenergic blockers (prazosin and tamsulosin). Though the LA does not function in its original capacity as fetal shunt, it is clearly not a passive structure, and may be described as muscular and contractile. The contractile abilities of LA myocytes may act on the two great vessels to which it is attached causing a change in their distensibility.
Topics: Animals; Mice; Humans; Swine; Aorta, Thoracic; Ductus Arteriosus, Patent; Ductus Arteriosus; Pulmonary Artery; Ligaments
PubMed: 36054486
DOI: 10.1002/ar.25058 -
International Braz J Urol : Official... 2023To evaluate the penile morphology after the isolated and combined administration of dutasteride and tamsulosin in a rodent model.
PURPOSE
To evaluate the penile morphology after the isolated and combined administration of dutasteride and tamsulosin in a rodent model.
MATERIALS AND METHODS
Forty male rats were assigned into the following groups: Control group (C, receiving distilled water, n=10); Dutasteride group (D, receiving 0.5 mg/Kg/day of dutasteride, n=10); Tamsulosin group (T, receiving 0.4 mg/Kg/day of tamsulosin, n=10); and Dutasteride associated with Tamsulosin group (DT, receiving both drugs n = 10). All drugs were administered via oral gavage. After 40 days, the animals were submitted to euthanasia and their penises were collected for histomorphometric analyses. Data were compared using one-way ANOVA followed by Bonferroni's post-test, considering p<0.05 as significant.
RESULTS
The sinusoidal space and smooth muscle fiber surface densities (Sv), and the cross-sectional penile areas of rats in groups D, T and DT were reduced in comparison to controls with the most notable reductions in the combined therapy group. The connective tissue and elastic system fibers Sv were augmented in groups D, T and DT in comparison with the control group, again with the most pronounced changes observed in animals receiving the combined therapy.
CONCLUSION
Both treatments with dutasteride or tamsulosin promoted penile morphometric modifications in a rodent model. The combination therapy resulted in more notable modifications. The results of this study may help to explain the erectile dysfunction observed in some men using these drugs.
Topics: Humans; Male; Rats; Animals; Dutasteride; Tamsulosin; 5-alpha Reductase Inhibitors; Prostatic Hyperplasia; Rodentia; Cross-Sectional Studies; Drug Therapy, Combination
PubMed: 37115177
DOI: 10.1590/S1677-5538.IBJU.2022.0583 -
Turkish Journal of Pharmaceutical... Aug 2018The present study was undertaken with the objective to develop and validate a simple spectrofluorimetric method for the simultaneous quantification of tamsulosin...
OBJECTIVES
The present study was undertaken with the objective to develop and validate a simple spectrofluorimetric method for the simultaneous quantification of tamsulosin hydrochloride and solifenacin succinate.
MATERIALS AND METHODS
First-derivative synchronous spectrofluorimetry was attempted for the simultaneous quantification of the analytes. Tamsulosin hydrochloride was quantified at a wavelength of 322 nm (zero-crossing wavelength point of solifenacin succinate) and solifenacin succinate was measured at 570 nm (zero-crossing wavelength point of tamsulosin hydrochloride).
RESULTS
Calibration plots were constructed over the concentration range of 2-10 µg/mL for tamsulosin hydrochloride and 30-150 µg/mL for solifenacin succinate. The method gave satisfactory results when it is validated for linearity, specificity, accuracy, precision, LOD and LOQ as per the ICH guidelines. The assay values in the commercial formulation were found to be in the percentage range of 95.0 for tamsulosin hydrochloride and 103.5 for solifenacin succinate by the proposed method. These results were well in agreement with their label claim.
CONCLUSION
The proposed synchronous analytical method can be employed for routine quality control analysis of tamsulosin hydrochloride/solifenacin succinate in tablet dose forms.
PubMed: 32454654
DOI: 10.4274/tjps.72692 -
Annals of Medicine and Surgery (2012) Aug 2022To date, no study evaluates the effect of atherosclerosis risk level on the efficacy of BPH drug therapies. Therefore, the present study aimed to assess the effect of...
INTRODUCTION
To date, no study evaluates the effect of atherosclerosis risk level on the efficacy of BPH drug therapies. Therefore, the present study aimed to assess the effect of atherosclerosis risk levels on the effectiveness of Tamsulosin and Tadalafil in LUTS treatment.
METHODS
The present study was a randomized clinical trial that assessed men with LUTS symptoms (at least six months). The inclusion criteria were being older than 50 years, international prostate symptom score (IPSS) ≥ 13, and maximum urinary flow rate (Qmax) between 4 and 15 ml/s. Framingham Risk Score was used to measure atherosclerosis risk. The patients were classified into four groups, including group 1: Patients with low risk and treated with Tamsulosin (0.4 mg/day), group 2: Patients with low risk and treated with Tadalafil (5 mg/day), group 3: Patients with high risk and treated with Tamsulosin (0.4 mg/day), group 4: Patients with high risk and treated with Tadalafil (5 mg/day).
RESULTS
The study included 44 and 38 patients receiving Tamsulosin and Tadalafil, respectively. The means (SD) of the baseline age for the Tamsulosin and Tadalafil groups were equal to 60.6 (6.8) and 58.8 (6.7), respectively (p-value = 0.213). The models revealed no impact of the atherosclerosis risk level on the drugs' effects (p-values = 0.378, 0.975, 0.743 for IPSS, QMAX, and VOID, respectively).
CONCLUSIONS
The present study's findings could not show the impact of atherosclerosis risk levels on the efficiency of Tamsolusin and Tadalafil in men with LUTS.
PubMed: 35846856
DOI: 10.1016/j.amsu.2022.104137 -
Nature Communications Jun 2023The αadrenergic receptor (αAR) belongs to the family of G protein-coupled receptors that respond to adrenaline and noradrenaline. αAR is involved in smooth muscle...
The αadrenergic receptor (αAR) belongs to the family of G protein-coupled receptors that respond to adrenaline and noradrenaline. αAR is involved in smooth muscle contraction and cognitive function. Here, we present three cryo-electron microscopy structures of human αAR bound to the endogenous agonist noradrenaline, its selective agonist oxymetazoline, and the antagonist tamsulosin, with resolutions range from 2.9 Å to 3.5 Å. Our active and inactive αAR structures reveal the activation mechanism and distinct ligand binding modes for noradrenaline compared with other adrenergic receptor subtypes. In addition, we identified a nanobody that preferentially binds to the extracellular vestibule of αAR when bound to the selective agonist oxymetazoline. These results should facilitate the design of more selective therapeutic drugs targeting both orthosteric and allosteric sites in this receptor family.
Topics: Humans; Oxymetazoline; Cryoelectron Microscopy; Receptors, Adrenergic, alpha-1; Norepinephrine; Tamsulosin
PubMed: 37339967
DOI: 10.1038/s41467-023-39310-x