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The aim of the present study was to compare the bioavailability and to demonstrate the bioequivalence between a dutasteride‐tamsulosin 0.5 mg/0.4 mg capsule formulation and the regulatory reference drug (Combodart®, GlaxoSmithKline). A randomized, single‐blind, single‐dose, 2‐way crossover study under fasting conditions, with at least a 28‐day washout period was carried out in healthy volunteers. Plasma concentrations of drugs were determined by high‐performance liquid chromatography–tandem mass spectrometry. The pharmacokinetic analysis included maximum plasma concentration (Cmax), area under the plasma concentration–time curve (AUC) from time 0 to 72 hours, and AUC from baseline to infinity. The test formulation was considered bioequivalent if the geometric mean ratios (test/reference) were within the predetermined range of 80% to 125%. Safety and tolerability were evaluated by clinical assessment. The confidence intervals for the log‐transformed test/reference ratios for dutasteride, Cmax (95.4‐109.2) and AUC from baseline to 72 hours (93.2‐109.1), and for tamsulosin, Cmax (101.9‐119.8), AUC from baseline to the last quantifiable concentration (91.4‐106.3) and AUC from baseline to infinity (90.9‐103.3), were within the allowed limit specified by the regulatory authorities (80%‐125%). In addition, both test and reference drugs were safe and tolerated. These results demonstrated the bioequivalence of test product (Dakart®) compared with Combodart®. [ABSTRACT FROM AUTHOR]

Abstract Background 5α-reductase inhibitors (5-ARIs) inhibit the pathway of converting the testosterone to dihydrotestosterone and are widely used in benign prostatic hyperplasia patients. Since androgen receptor activation may play a role in urothelial tumorigenesis, we conducted this retrospective cohort study to determine whether 5α-reductase inhibitors (5-ARIs) administration is associated with bladder cancer mortality, bladder cancer recurrence and upper tract urothelial carcinoma mortality, using the Taiwan National Health Insurance database. Methods The data of this retrospective cohort study were sourced from the Longitudinal Health Insurance Database of Taiwan, compiled by the Taiwan National Health Insurance database from 1996 to 2010. It consists of 18,530 men with bladder cancer, of whom 474 were 5-ARIs recipients and 4384 men with upper tract urothelial carcinoma, of whom 109 were 5-ARIs recipients. Propensity Score Matching on the age and geographic data was done at the ratio of 1:10. We analyzed the odds ratios (OR) and 95% confidence interval (CI) of the risk of bladder cancer death, bladder cancer recurrence rate and upper tract urothelial carcinoma related death by the 5-ARIs administration. Results Those who received 5-ARIs showed a lower risk of bladder cancer related death compared to nonusers in multivariable adjusted analysis (OR 0.835, 95% CI 0.71–0.98). However, there was no significant difference in the bladder cancer recurrence rate (OR 0.956, 95% CI 0.82–1.11) and upper tract urothelial carcinoma related mortality in multivariable adjusted analysis (OR 0.814, 95% CI 0.6–1.1). Conclusions Patients who receive 5-ARIs have lower bladder cancer related mortality compared to those who don’t. 5-ARIs may prove to be a viable strategy to improve bladder cancer outcomes.

Abstract Glutamate toxicity is a pathomechanism that contributes to neuronal cell death in a wide range of acute and chronic neurodegenerative and neuroinflammatory diseases. Activation of the N-methyl-D-aspartate (NMDA)-type glutamate receptor and breakdown of the mitochondrial membrane potential are key events during glutamate toxicity. Due to its manifold functions in nervous system physiology, however, the NMDA receptor is not well suited as a drug target. To identify novel compounds that act downstream of toxic NMDA receptor signaling and can protect mitochondria from glutamate toxicity, we developed a cell viability screening assay in primary mouse cortical neurons. In a proof-of-principle screen we tested 146 natural products and 424 FDA-approved drugs for their ability to protect neurons against NMDA-induced cell death. We confirmed several known neuroprotective drugs that include Dutasteride, Enalapril, Finasteride, Haloperidol, and Oxybutynin, and we identified neuroprotective properties of Elvitegravir. Using live imaging of tetramethylrhodamine ethyl ester-labelled primary cortical neurons, we found that Elvitegravir, Dutasteride, and Oxybutynin attenuated the NMDA-induced breakdown of the mitochondrial membrane potential. Patch clamp electrophysiological recordings in NMDA receptor-expressing HEK293 cell lines and primary mouse hippocampal neurons revealed that Elvitegravir does not act at the NMDA receptor and does not affect the function of glutamatergic synapses. In summary, we have developed a cost-effective and easy-to-implement screening assay in primary neurons and identified Elvitegravir as a neuro- and mitoprotective drug that acts downstream of the NMDA receptor.

Background: The aim of this research is to study the influence of simultaneous taking of tadalafil and solifenacin in standard and double dosage on the lower urinary tract symptoms (LUTS) and sexual dysfunction in men with benign prostatic hyperplasia after the course of dutasteride. Materials and methods: The research included 326 patients older than 50 years with benign prostatic hyperplasia coupled with LUTS and sexual dysfunction having undergone the course of treatment with dutasteride. After random division into three groups, patients from the Group A (n = 107) got tadalafil 5 mg/d as monotherapy, from the Group В (n = 107) got tadalafil 5 mg/d and solifenacin 10 mg/d, and from the Group С (n = 112) got tadalafil 5 mg/d and solifenacin 20 mg/d. The duration of treatment was 12 weeks. The rating of sexual function was made with the questionnaires International Index of Erectile Function and other. Results: The results of rating of sexual function with the questionnaires MSHQ-EjD and International Index of Erectile Function correlated among themselves. According to MSHQ-EjD, overall rating of the sexual function increased in each of the three groups (A: 67.9 (12.4)/91.5 (10.4), P ≤ 0.05; B: 72.4 (14.5)/102.6 (16.9), P ≤ 0.05; C: 76.6 (16.3)/109.6 (15.6), P ≤ 0.05). The level of hyperactivity symptoms decreased in Groups В and С (В: urgency −2.9 (0.7)/1.1 (0.6), P ≤ 0.05; nocturia 2.7 (1.0)/0.7 (0.5), P ≤ 0.05; C: urgency −2.5 (0.5)/0.8 (0.6), P ≤ 0.05; nocturia −2.8 (0.6)/1.0 (0.5), P ≤ 0.05), and it did not change in the Group A. Conclusions: The use of tadalafil as monotherapy significantly improves the sexual function but does not affect overactive bladder symptoms. The combination therapy of tadalafil and solifenacin leads to dramatic improvement of sexual function and reversibility of detrusor hyperactivity symptoms.

Abstract Background Ankylosing spondylitis (AS) is characteristically male-predominant, and progressive spinal ankylosis affects male patients more severely; however, the hormonal effects in males with AS are poorly understood. Methods In the present study, the regulatory effects of dutasteride, a 5-α reductase inhibitor that blocks the conversion of testosterone to dihydrotestosterone (DHT), were examined in curdlan-administered male SKG mice to determine spinal bone formation, bone metabolism-related markers, and interleukin (IL)-17A cytokine and T cell populations. In addition, the effects of DHT on primary osteoprogenitors from the facet joints of AS patients were assessed based on osteoblast-related parameters. DHT level was measured, and the correlation with modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) was analyzed in AS patients. Results In curdlan-administered SKG mice, dutasteride treatment resulted in an increased accumulation of hydroxyapatite in the spine which was positively correlated with serum IL-17A levels. In the analysis of bone metabolism-related molecules, a decrease in sclerostin levels was observed in the sera in the dutasteride group. Continuous exposure to DHT resulted in fewer calcium deposits in AS osteoprogenitors during osteoblast differentiation. DHT-treated AS osteoprogenitors showed decreased osteocalcin and increased DKK1 and SOST1 mRNA expression, supporting the results of the in vivo experiments. Treatment with dutasteride upregulated bone formation in the spine of curdlan-administered SKG mice and DHT treatment downregulated osteoblast differentiation in vitro. Conclusions Treatment with dutasteride affected the bone formation in the spine of curdlan-treated SKG mice, and DHT treatment attenuated osteoblast differentiation in vitro. Therefore, contrary to what could be expected if osteoblasts contributed to spinal ankylosis, DHT inhibition might increase rather than decrease the progression of spinal ankylosis despite the higher levels of DHT observed in many AS patients.

Trans Urethral Resection of the Prostate (TURP) is one of the gold operating standards for people with Benign Prostate Hyperplasia (BPH), but the complications, like bleedings, often occur both in durante and post-surgery. The risk of bleeding in TURP is caused by angiogenesis. Hypoxia-Induced Factor-1 Alpha (HIF-1 α) is one of the trigger factors for angiogenesis in BPH. Based on the existing literature, it was found that there was a relationship between lycopene and dutasteride which both had a synergistic effect in inhibiting angiogenesis. However, the mechanism is unknown. This study aims to assess the effectiveness of the combination of dutasteride and lycopene on the expression of HIF-1α and hematocrit levels in BPH patients undergoing TURP surgery. This research was an experimental study with "Double-Blind Randomized Controlled Trial Post Test Only Design". The 22 patients were divided into 2 groups, namely T (dutasteride + lycopene), C (lycopene+plasebo), which were given every 24 hours for a minimum of 30 days until the TURP operation was carried out. The observation of HIF-1α expression used immunohistochemical methods. Different tests were conducted between the groups with Independent T-test. The result shows the combination of dutasteride and lycopene was not significant in reducing the HIF-1α expression, indicated by mean rank in the group (C) (= 21.60), group (T) (= 20.00). The results obtained from the Independent T-test were (p = 0.410), meaning the difference in HIF-1α expression between the 2 groups was not significant: Average Δ Ht group C (= 1.26); group T (= -0,98). The statistical test with the Independent T-test obtained (p = 0.027), where there were significant differences. Giving a combination of dutasteride and lycopene for at least 30 days pre-TURP surgery was not effective in reducing the expression of hypoxia-induced factor - 1 alpha (HIF-1α) but was effective in reducing hematocrit levels compared to a single administration of dutasteride in BPH patients undergoing TURP surgery.

Wimolsiri Iamsumang, Kanchana Leerunyakul, Poonkiat Suchonwanit Division of Dermatology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, ThailandCorrespondence: Poonkiat Suchonwanit Email poonkiat@hotmail.comAbstract: The currently approved treatment for female pattern hair loss (FPHL) includes topical minoxidil administration; however, this treatment fails to achieve hair regrowth in some patients. Finasteride, a selective 5α-reductase inhibitor (5-ARI), may be considered as an alternative treatment. However, because of its potential teratogenic effects, clinical studies and use of finasteride for FPHL are limited. In this review, we aim to summarize the literature regarding the pharmacology, clinical efficacy, and adverse effects of oral finasteride for the treatment of FPHL and to provide novel therapeutic options including topical finasteride and dutasteride, a new generation 5-ARI, for the treatment of FPHL.Keywords: alopecia, androgenetic alopecia, dutasteride, hair loss, topical finasteride, therapy