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PloS One 2019Dutasteride, a dual inhibitor of both type I and II 5α-reductases, is used to treat male pattern hair loss (MPHL). However, patient response to dutasteride varies in...
Dutasteride, a dual inhibitor of both type I and II 5α-reductases, is used to treat male pattern hair loss (MPHL). However, patient response to dutasteride varies in each individual, the cause of which is yet to be identified. To identify genetic variants associated with response to dutasteride treatment for MPHL, a total of 42 men with moderate MPHL who had been treated with dutasteride for 6 months were genotyped and analysed by quantitative linear regression, case-control association tests, and Fisher's exact test. The synonymous single nucleotide polymorphism (SNP) rs72623193 in DHRS9 was most significantly associated with response to dutasteride, followed by the non-synonymous SNP rs2241057 in CYP26B1. Additionally, variants in ESR1, SRD5A1, CYP19A1, and RXRG are suggested to be associated with response to dutasteride. Cumulative effect and interaction among these SNPs were presented in both additive and non-additive models.
Topics: 5-alpha Reductase Inhibitors; Adult; Alopecia; Case-Control Studies; Dutasteride; Hair; Humans; Male; Middle Aged; Polymorphism, Single Nucleotide; Young Adult
PubMed: 31525235
DOI: 10.1371/journal.pone.0222533 -
Bioengineering (Basel, Switzerland) Jan 2022Male pattern baldness (MPB) is a common condition that has a negative impact on the psycho-social health of many men. This study aims to engineer an alcohol-free...
Male pattern baldness (MPB) is a common condition that has a negative impact on the psycho-social health of many men. This study aims to engineer an alcohol-free formulation to cater for individuals who may have had allergic reactions to alcohol-based preparations. A lipid-based nanoparticle system composed of stearic and oleic acid (solid and liquid lipid) was used to deliver dutasteride (DST) for topical application. Two compositions, with oleic acid (Formulation A) and without (Formulation B), were compared to analyse the role of oleic acid as a potential active ingredient in addition to DST. DST-loaded LNP were prepared using the emulsification-ultrasonication method. All of the prepared formulations were spherical in shape in the nanometric size range (150-300 nm), with entrapment efficiencies of >75%. X-ray diffractograms revealed that DST exists in an amorphous form within the NLP matrices. The drug release behaviour from both LNP preparations displayed slow release of DST. Permeation studies through pig ear skin demonstrated that DST-LNP with oleic acid produced significantly lower permeation into the dermis compared to the formulation without oleic acid. These results suggest that the proposed formulation presents several characteristics which are novel, indicating its suitability for the dermal delivery of anti-androgenic molecules.
PubMed: 35049720
DOI: 10.3390/bioengineering9010011 -
BMC Research Notes Sep 2022To evaluate the efficacy and safety of add-on therapy with the phosphodiesterase type 5 inhibitor tadalafil in Japanese men with lower urinary tract symptoms (LUTS) due...
OBJECTIVE
To evaluate the efficacy and safety of add-on therapy with the phosphodiesterase type 5 inhibitor tadalafil in Japanese men with lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) treated with dutasteride.
RESULTS
Twenty-four patients were enrolled. The participants had a median age of 71.0 (64.8-73.0) years and a median prostate volume of 37.3 (29.7-41.8) mL as measured using transabdominal sonography. The efficacy indicators, such as International Prostate Symptom Score (IPSS), quality of life (QOL) score, night-time urinary frequency, and night-time maximum voided volume, improved significantly at 4 weeks, and the effects lasted until 24 weeks (IPSS: 9.5 vs. 17.0, QOL: 2.0 vs. 4.0, nocturia: 2.0 vs. 2.0, night-time maximum voided volume: 290.0 vs. 240.0 mL). Overactive bladder symptom score (OABSS) and sexual health inventory for men (SHIM) significantly improved at 12 weeks, and the effects lasted until 24 weeks (OABSS: 3.0 vs. 5.0, SHIM: 11.0 vs. 7.5). However, maximum urine flow and residual urine volume showed no improvement at any point. Adverse events occurred in two cases. Taken together, add-on therapy with tadalafil was effective for patients with LUTS/BPH resistant to dutasteride monotherapy. In addition, this therapy was not associated with severe adverse events.
Topics: Aged; Dutasteride; Humans; Lower Urinary Tract Symptoms; Male; Prostatic Hyperplasia; Quality of Life; Tadalafil; Urinary Bladder, Overactive
PubMed: 36064733
DOI: 10.1186/s13104-022-06183-0 -
Medical Archives (Sarajevo, Bosnia and... 2023The α-adrenergic receptor antagonist is the most effective medical therapy to reduce the dynamic component in patients with BPH. However, long-term administration of...
BACKGROUND
The α-adrenergic receptor antagonist is the most effective medical therapy to reduce the dynamic component in patients with BPH. However, long-term administration of receptor antagonists can cause upregulation of mRNA receptor expression, resulting in tolerance of drug effectiveness. PKC-α is involved in the process of prostate smooth muscle contraction through activation of the voltage-gated Ca2+ conducted canal, influenced by androgen hormones, especially testosterone, and has an isoform with Twist1, a transcription factor that plays a role in up-regulation of androgen receptors.
OBJECTIVE
The aim of the study was to compare the effect of long-term tamsulosin monotherapy and tamsulosin - dutasteride combination therapy in PKC-α enzyme expression in prostate stromal tissue of Rattus norvegicus rats of Wistar strain.
METHODS
Out of 80 samples of Rattus norvegicus rats were divided into 8 groups with different interventions: negative control group, positive control group, tamsulosin monotherapy administration for 1 day, 3 day, and 6 day groups, and tamsulosin - dutasteride combination therapy for 1 day, 3 day, and 6 day groups. BPH was induced with 3 mg/kg of testosterone proprionate for 3 weeks, continued with drugs administration according to intervention grouping. Prostate stromal tissue was taken and prepared for PKC-α enzyme measurement with ELISA method.
RESULTS
There was a significant difference (p<0.05) in the effect of tamsulosin monotherapy and tamsulosin-dutasteride combination therapy on the PKC-α expression. There was a strong positive relationship between the duration of tamsulosin-dutasteride combination therapy on the PKC-α expression, which means the longer the duration of the combination of tamsulosin-dutasteride combination the higher the PKC-α expression.
CONCLUSION
Administration of long-term tamsulosin - dutasteride combination therapy causes upregulation PKC-α expression more than tamsulosin only.
Topics: Animals; Male; Rats; 5-alpha Reductase Inhibitors; Azasteroids; Drug Therapy, Combination; Dutasteride; Prostate; Prostatic Hyperplasia; Rats, Wistar; Sulfonamides; Tamsulosin; Testosterone
PubMed: 38313112
DOI: 10.5455/medarh.2023.77.446-450 -
Medicina (Kaunas, Lithuania) Sep 2023: Androgenetic alopecia (AGA) and alopecia areata (AA) are the most common types of non-cicatricial alopecia. Both diseases have limited effective therapeutic options...
: Androgenetic alopecia (AGA) and alopecia areata (AA) are the most common types of non-cicatricial alopecia. Both diseases have limited effective therapeutic options and affect patient quality of life. Pharmacogenetic tests can help predict the most appropriate treatment option by evaluating the single nucleotide polymorphisms (SNPs) corresponding to genes related to alopecia. The objective of the study was to evaluate and compare selected SNPs and genes in AA and AGA patients from Romania and Brazil. : We performed a retrospective study regarding the associations between AA and AGA and 45 tag SNPs of 15 genes in 287 Romanian and 882 Brazilian patients. The DNA samples were collected from oral mucosa using a swab. The SNPs were determined by the qPCR technique. Each genetic test displays the subject's genotype of the selected gene and the prediction of a successful treatment (e.g., genotype AA of the GR-alpha gene is related to a predisposition to normal sensibility to topical glucocorticoid, and, therefore, glucocorticoids should be effective). : The , , , and genes were statistically significantly different in Brazil compared to Romania. The activity that predicts the response to minoxidil treatment showed in our analysis that minoxidil is recommended in half of the cases of AGA and AA. Patients with AGA and a high expression of or -2 may benefit from Dutasteride or Latanoprost treatment, respectively. Most of the studied genes showed no differences between the two populations. : The DNA analysis of the patients with alopecia may contribute to a successful treatment.
PubMed: 37763773
DOI: 10.3390/medicina59091654 -
Asian Journal of Urology Jan 2022Bleeding is one of the most common complications of transurethral resection of the prostate (TURP). Several previous studies reported that administering dutasteride...
The role of preoperative dutasteride in reducing bleeding during transurethral resection of the prostate: A systematic review and meta-analysis of randomized controlled trials.
OBJECTIVE
Bleeding is one of the most common complications of transurethral resection of the prostate (TURP). Several previous studies reported that administering dutasteride before surgery could reduce perioperative bleeding. We aimed to evaluate the efficacy of preoperative dutasteride treatment in benign prostatic hyperplasia patients undergoing TURP by performing a meta-analysis of relevant randomized controlled trials (RCTs).
METHODS
A comprehensive literature search was performed through the electronic databases including Medline, Cochrane Library, Google Scholar, and ClinicalTrial.gov in October 2020. RCTs evaluating the role of dutasteride for TURP were screened using the eligibility criteria and the quality of RCTs was assessed using the Cochrane Risk of Bias Tool. The heterogeneity was assessed using statistic. The measured outcomes were hemoglobin (Hb) levels, perioperative blood loss, blood transfusion, microvessel density (MVD), and operation time. Data were pooled as mean difference (MD) and odds ratio (OR).
RESULTS
A total of 11 RCTs consisting of 627 samples from the treatment group and 615 samples from the placebo group were analyzed. Patients that received dutasteride had less reduction in Hb levels (MD -1.10, 95% confidence interval [CI] -1.39 to -0.81, <0.00001). Dutasteride also significantly reduced the operation time (MD -1.79, 95% CI -2.97 to -0.61, =0.003) and transfusion rate after surgery (OR 0.34, 95% CI 0.15 to 0.77, =0.009) compared to the control group. However, the MVD (MD -3.60, 95% CI -8.04 to 0.84, =0.11) and perioperative blood loss in dutasteride administration for less than 4 weeks (MD 46.90, 95% CI -144.60 to 238.41, =0.63) and more than 4 weeks (MD -190.13, 95% CI -378.05 to -2.21, =0.05) differences were insignificant.
CONCLUSION
Preoperative administration of dutasteride is able to reduce bleeding during TURP, as indicated by less reduction in Hb level, lower transfusion rate, and less operation time.
PubMed: 35198393
DOI: 10.1016/j.ajur.2021.05.011 -
Molecular Brain Sep 2020Glutamate toxicity is a pathomechanism that contributes to neuronal cell death in a wide range of acute and chronic neurodegenerative and neuroinflammatory diseases....
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.
Topics: Animals; Antiviral Agents; Cell Death; Cells, Cultured; Channelrhodopsins; Drug Approval; Excitatory Postsynaptic Potentials; HEK293 Cells; Humans; Membrane Potential, Mitochondrial; Mice, Inbred C57BL; Microscopy; N-Methylaspartate; Neurons; Neuroprotection; Neuroprotective Agents; Optogenetics; Quinolones; Receptors, AMPA; Receptors, Glutamate; Receptors, N-Methyl-D-Aspartate; Small Molecule Libraries; Synapses; United States; United States Food and Drug Administration
PubMed: 32928261
DOI: 10.1186/s13041-020-00641-1 -
Sexual Medicine Oct 2022Erectile dysfunction (ED) is an adverse effect of many medications.
BACKGROUND
Erectile dysfunction (ED) is an adverse effect of many medications.
AIM
We used a national pharmacovigilance database to assess which medications had the highest reported frequency of ED.
METHODS
The Food and Drug Administration Adverse Event Reporting System (FAERS) was queried to identify medications with the highest frequency of ED adverse event reports from 2010 to 2020. Phosphodiesterase-5 inhibitors and testosterone were excluded because these medications are often used as treatments for men with ED. The 20 medications with the highest frequency of ED were included in the disproportionality analysis.
OUTCOMES
Proportional Reporting Ratios (PRRs) and their 95% confidence intervals were calculated.
RESULTS
The 20 medications accounted for 6,142 reports of ED. 5-α reductase inhibitors (5-ARIs) and neuropsychiatric medications accounted for 2,823 (46%) and 2,442 (40%) of these reports respectively. Seven medications showed significant levels of disproportionate reporting with finasteride and dutasteride having the highest PRRs: 110.03 (103.14-117.39) and 9.40 (7.83-11.05) respectively. The other medications are used in a wide variety of medical fields such as cardiology, dermatology, and immunology.
CLINICAL IMPLICATIONS
Physicians should be familiar with these medications and understand their respective mechanisms of action, so that they may counsel patients appropriately and improve their quality of life.
STRENGTHS AND LIMITATIONS
The strength of the study is its large sample size and that it captures pharmacologic trends on a national level. Quantitative and comparative "real-world" data is lacking for the most common medications associated with ED. The limitation is that the number of reported events does not establish causality and cannot be used to calculate ED incidence rates.
CONCLUSION
In a national pharmacovigilance database, 5-ARIs and neuropsychiatric medications had the highest reports of ED adverse effects. There were many other medications used in a variety of medical fields that were also associated with ED. Kaplan-Marans E, Sandozi A, Martinez M, et al. Medications Most Commonly Associated With Erectile Dysfunction: Evaluation of the Food and Drug Administration National Pharmacovigilance Database. Sex Med 2022;10:100543.
PubMed: 35843193
DOI: 10.1016/j.esxm.2022.100543 -
Medical Archives (Sarajevo, Bosnia and... 2023Benign prostate hyperplasia (BPH) is frequently found in the elderly and significantly impacts the quality of life. One of the risk factors that induce BPH is the...
BACKGROUND
Benign prostate hyperplasia (BPH) is frequently found in the elderly and significantly impacts the quality of life. One of the risk factors that induce BPH is the androgen hormone. One of the effective medications in reducing the severity of Lower Urinary Tract Symptoms caused by BPH is the α-adrenergic receptor 5α-reductase inhibitor.
OBJECTIVE
The study aims to see the effect of long-term dutasteride on the expression of the PKC-α enzyme in prostatic stromal tissue in the BPH Model of Wistar strain Rattus norvegicus rats.
METHOD
This study was an experimental, post-test-only, control group design that used randomization in sample selection. The objective is to measure the expression of PKC-α enzyme from prostate tissue of an adult male Wistar Strain of Rattus Novergicus rat that was given testosterone to induce BPH and given dutasteride in 1,3 and 6 days continuously. Data is shown in mean±SD, and all of the data were analyzed using the software SPSS 21st version with the One Way ANOVA Statistical method after fulfilling the normality test and variant homogeneity test. Data analysis with confidence rate 95% and a=0,05.
RESULTS
There was a decrease of PKC-α enzyme and prostate weight in dutasteride monotherapy in 1,3,6 days compared to the positive control, and the lowest value was on the sixth day (SD ± 2876.8). There was a constant decrease of PKC-α enzyme from the first day until the sixth day.
CONCLUSION
In conclusion, long-term dutasteride monotherapy could significantly decrease the level of PKC-α enzyme. There was no upregulation of the PKC-α enzyme in the long term of dutasteride monotherapy.
Topics: Male; Rats; Animals; Humans; Dutasteride; Prostatic Hyperplasia; Rats, Wistar; Protein Kinase C-alpha; Quality of Life
PubMed: 37700916
DOI: 10.5455/medarh.2023.77.202-206 -
Journal of AOAC International Oct 2022Tamsulosin (TAM) and dutasteride (DUT) are ranked among the most frequently prescribed therapies in urology. Interestingly, studies have also been carried out on TAM/DUT...
BACKGROUND
Tamsulosin (TAM) and dutasteride (DUT) are ranked among the most frequently prescribed therapies in urology. Interestingly, studies have also been carried out on TAM/DUT in terms of their ability to protect against recent COVID-19. However, very few studies were reported for their simultaneous quantification in their combined dosage form and were mainly based on chromatographic analysis. Subsequently, it is very important to offer a simple, selective, sensitive, and rapid method for the quantification of TAM and DUT in their challenging dosage form.
OBJECTIVE
In this study, a new chemometrically assisted ultraviolet (UV) spectrophotometric method has been presented for the quantification of TAM and DUT without any prior separation.
METHOD
For the calibration set, a partial factorial experimental design was used, resulting in 25 mixtures with central levels of 20 and 25 μg/mL for TAM and DUT, respectively. In addition, to assess the predictive ability of the developed approaches, another central composite design of 13 samples was used as a validation set. Post-processing by chemometric analysis of the recorded zero-order UV spectra of these sets has been applied. These chemometric approaches include partial least-squares (PLS) and genetic algorithm (GA), as an effective variable selection technique, coupled with PLS.
RESULTS
The models' validation criteria displayed excellent recoveries and lower errors of prediction.
CONCLUSIONS
The proposed models were effectively used to determine TAM/DUT in their combined dosage form, and statistical comparison with the reported method revealed satisfactory results.
HIGHLIGHTS
Overall, this work presents powerful simple, selective, sensitive, and precise methods for simultaneous quantification of TAM/DUT in their dosage form with satisfactory results. The predictive ability and accuracy of the developed methods offer the opportunity to be employed as a quality control technique for the routine analysis of TAM/DUT when chromatographic instruments are not available.
Topics: Humans; Dutasteride; Tamsulosin; Research Design; COVID-19; Spectrophotometry, Ultraviolet; Least-Squares Analysis; Calibration; Pharmaceutical Preparations; Spectrophotometry
PubMed: 35758559
DOI: 10.1093/jaoacint/qsac080