• Biomolecules & Therapeutics
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• v.21 no.1
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• pp.49-53
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• 2013

A number of naturally-occurring or synthetic chemicals have been reported to exhibit prostate chemopreventive effects. Synthetic $5{\alpha}$-reductase (5-AR) inhibitors, e.g. finasteride and durasteride, gained special interests as possible prostate chemopreventive agents. Indeed, two large-scale epidemiological studies have demonstrated that finasteride or durasteride significantly reduced the incidence of prostate cancer formation in men. However, these studies have raised an unexpected concern; finasteride and durasteride increased the occurrence of aggressive prostate tumor formation. In the present study, we have observed that treatment of finasteride did not affect the growth of androgen-refractory PC-3 prostate cancer cells. Finasteride also failed to induce apoptosis or affect the expression of proto-oncogenes in PC-3 cells. Interestingly, we found that treatment of finasteride induced the expression of Nrf2 and HO-1 proteins in PC-3 cells. In particular, basal level of Nrf2 protein was higher in androgen-refractory prostate cancer cells, e.g. DU-145 and PC-3 cells, compared with androgen-responsive prostate cancer cells, e.g. LNCaP cells. Also, treatment of finasteride resulted in a selective induction of Nrf2 protein in DU-145 and PC-3 cells, but not in LNCaP cells. In view of the fact that upregulation of Nrf2-mediated phase II cytoprotective enzymes contribute to attenuating tumor promotion in normal cells, but, on the other hand, confers a selective advantage for cancer cells to proliferate and survive against chemical carcinogenesis and other forms of toxicity, we propose that finasteride-mediated induction of Nrf2 protein might be responsible, at least in part, for an increased risk of high-grade prostate tumor formation in men.

• Biomolecules & Therapeutics
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• v.19 no.2
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• pp.231-236
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• 2011

The aim of this study was to investigate the effect of charge carrier lipid on the skin penetration, retention, and hair growth of topically applied finasteride-containing liposomes. Finasteride-containing liposomes were prepared by traditional thin film hydration method using Phospholipon$^{(R)}$ 85 G and cholesterol with or without charge carrier lipid (1,2 dimyristoyl-sn-glycero-3-phosphate or 1,2-dioleoyl-trimethylammonium-propane for anionic and cationic charge, respectively). Freshly prepared finasteride-containing liposome suspension was applied on the hairless mouse skin, and skin penetration and retention were measured using Keshary-Chien diffusion cell. Non-liposomal formulation (ethanol 10% solution containing 0.5 mg/ml of FNS) was also used as a control. The amount of finasteride in the diffusion cell and mouse skin was measured by HPLC. The hair growth was evaluated using depilated male C57BL/6N mice. Mean particle size of all finasteride-containing liposomes was less than a micron, and polydispersity index revealed size homogeneity. Skin penetration and retention studies showed that significantly less amount of finasteride was penetrated when applied as anionic liposome while more amount of the drug was retained. Specifically, in liposome prepared with 10% anionic charge carrier lipid, penetration was 12.99 ${\mu}g/cm^2$ while retention was 79.23 ${\mu}g/cm^2$ after 24 h of application. In hair growth study, finasteride-containing anionic liposomes showed moderate efficacy, but the efficacy was not found when applied as cationic liposomes. In conclusion, topical application of finasteride using anionic liposome formulation appears to be useful option for the treatment of androgenetic alopecia to avoid systemic side effects of the drug.

• Korean Journal of Clinical Pharmacy
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• v.31 no.4
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• pp.324-331
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• 2021

To investigate signals of adverse drug reactions of finasteride by using the Korea Adverse Events Reporting System (KAERS) database. This pharmacovigilance was based on the database of the drug-related adverse reactions reported spontaneously to the KAERS from 2013 to 2017. This study was conducted by disproportionality analysis. Data mining analysis was performed to detect signals of finasteride. The signal was defined by three criteria as proportional reporting ratio (PRR), reporting odds ratio (ROR), and information component (IC). The signals of finasteride were compared with those of the other drugs; dutasteride (similar mechanism of action), minoxidil (different mechanism but similar indications for alopecia), silodosin (different mechanism but similar indications for BPH). It was examined whether the detected signals exist in drug labels in Korea. The total number of adverse event-drug pairs was reported 2,665,429 from 2013 to 2017, of which 1,426 were associated with finasteride. The number of investigated signals of finasteride was 42. The signals that did not include in the drug label were 29 signals, including mouth dry, hypotension, dysuria etc. The signal of finasteride was similar to that of dutasteride and silodosin but was different to that of minoxidil. Early detection of signals through pharmacovigilance is important to patient safety. We investigated 29 signals of finasteride that do not exist in drug labels in Korea. Further pharmacoepidemiological studies should be needed to evaluate the signal causality with finasteride.

• Journal of the Korean Society of Industry Convergence
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• v.16 no.3
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• pp.69-74
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• 2013

Finasteride, ($5{\alpha}$, $17{\beta}$)-N-(1,1-dimethylethyl)-3-oxo-4-azaandrost-1-ene-17-carboxamide), is a 5a-reductase enzyme inhibitor. This enzyme converts testosterone to the more potent androgen, a-dihydrotestosterone. This molecules a logical medical treatment for benign prostatic hyperplasia (BPH), as it induced a reduction in serum dihydrotestosterone and prostatic specific antigen levels with a concomittant increase in blood testosterone concentration . Despite its widespread use, little has been published concerning its molecular properties. Therefore, in this study, in order to explain characteristics of finasteride, total energy, net charge, vibrational mode of melatonin are calculated by PM3 methods of HyperCam 8.0.

• Korean Chemical Engineering Research
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• v.59 no.3
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• pp.455-466
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• 2021

Micro and nanoparticles of Finasteride were prepared by gas-antisolvent method. The influence of process parameters such as pressure (100, 130 and 160 bar), temperature (308, 318 and 328 K) and solute concentrations (10, 25 and 40 mg/ml) on mean particle size was studied by Box-Behnken design. As ANOVA results indicated, the highest influence in production of smaller particles was attributed to the pressure. Optimum condition leading to the smallest particle size was as follows: initial solute concentration, 10 mg/ml; temperature, 308 K and pressure, 160 bar. The particles were evaluated with FTIR, SEM, DLS, XRD as well as DSC. The analyses revealed a size decrease in the precipitated Finasteride particles (232.4 nm, on mean) via gas-antisolvent method, as compared to the original particles (55.6 ㎛).

• The Journal of Korean Medicine
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• v.42 no.4
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• pp.10-24
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• 2021

Objectives: Yongdamsagan-tang (YST) and Paljung-san (PJS) in traditional medicine and finasteride in modern medicine are used to treat benign prostatic hyperplasia (BPH). In recent, the use of combination herbal remedies with conventional drugs has been increasing. Therefore, we investigated the anti-inflammatory effects of these drugs to treat BPH and the influence of herbal formulas on finasteride metabolism. Methods: The inhibitory effects of the herbal formulas and finasteride on the production of inflammatory mediators and cytokines were determined in lipopolysaccharide (LPS)-treated RAW 264.7 cells. Additionally, the influence of herbal formulas on activities of human drug metabolizing enzymes (DMEs) was assessed using human microsomal enzymes. Results: We observed that YST, PJS and finasteride inhibited the production of nitric oxide (NO), prostaglandin E₂ (PGE₂) and interleukin-6 (IL-6) in RAW 264.7 cells. The half maximal inhibitory concentration (IC₅₀) of YST on PGE₂ production was calculated to be below 25 ㎍/mL. YST inhibited the activity of uridine diphosphate-glucuronosyltransterase (UGT) 1A4 with an IC₅₀ value of 49.35 ㎍/mL. The activities of cytochrome P450 (CYP) 1A2, CYP2B6, CYP2C19, CYP3A4, and UGT1A1 were inhibited by PJS (IC₅₀ < 100 ㎍/mL, each). Although PJS and YST inhibited the activities of CYP3A4 and UGT1A4, respectively, these formulas may not influence the metabolism of finasteride because the IC₅₀ values of herbal formulas on DMEs are too high to affect metabolism. Conclusions: Our results suggest that the combination of finasteride and YST or PJS might not influence their drug metabolism and that the drugs may have synergistic effects against BPH.

• Journal of Pharmaceutical Investigation
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• v.36 no.2
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• pp.143-148
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• 2006

Finasteride $[N-(1, 1-dimethylethyl)-3-oxo-4-aza-5{\alpha}-androst-1-ene-17{\beta}-carboxamide]$ is a 4-aza-3-oxosteroidal inhibitor of human $5{\alpha}-reductase$. The purpose of the present study was to evaluate the bioequivalence of two finasteride tablets, $Proscar^{\circledR}$ (MSD Korea Ltd.) and Procare (Hana Pharm. Co., Ltd.), according to the guidelines of the Korea Food and Drug Administration (KFDA). The release of finasteride from the two finasteride formulations in vitro was tested using KP VIII Apparatus II method with various dissolution media (pH 1.2, 4.0, 6.8 buffer solution and water). Twenty six healthy male subjects, $23.7\;{\pm}\;2.24$ years in age and $67.2\;{\pm}\;8.55\;kg$ in body weight, were divided into two groups and a randomized $2\;{\time}\;2$ cross-over study was employed. After two tablets containing 5 mg as finasteride was orally administered, blood samples were taken at predetermined time intervals and the concentrations of finasteride in serum were determined using HPLC with UV detector. The dissolution profiles of two formulations were similar in all tested dissolution media. The pharmacokinetic parameters such as $AUC_t,\;C_{max},\;and\;T_{max}$ were calculated and ANOVA test was utilized for the statistical analysis of the parameters using logarithmically transformed $AUC_t,\;C_{max}$ and untransformed $T_{max}$. The results showed that the differences between two formulations based on the reference drug, $Proscar^{\circledR}$, were 6.39, 4.65 and -13.9% for $AUC_t,\;C_{max},\;and\;T_{max},$ respectively. There were no sequence effects between two formulations in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log 0.800 to log 1.25 $(e.g.,\;log\;0.990{\sim}log\;1.14\;and\;log\;0.977{\sim}log\;1.13 for\;AUC_t\;and\;C_{max},\;respectively)$. Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating Procare tablet was bioequivalent to $Proscar^{\circledR}$ tablet.

• Korean Journal of Clinical Pharmacy
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• v.25 no.3
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• pp.171-177
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• 2015

Background: Androgenetic alopecia (AGA), one of alopecias, requires continuous treatment in order to prevent or stop it, and patient's compliance is very important. Currently, only two drugs (finasteride, minoxidil) have been approved for AGA by Food and Drug Administration of United States (US FDA). However, another ${\alpha}-2$ reductase inhibitor, dutasteride, is approved by Korea Ministry of Food and Drug Safety (MFDS) through a phase III trial. For treatment, pharmacotherapy of AGA usually combines topical minoxidil 7% with one of oral <${\alpha}-2$ reductase inhibitor. Objectives: We evaluated the comparative efficacy and adverse effect between topical minoxidil 7%/finasteride 1 mg and topical minoxidil 7%/dutasteride 0.5 mg pharmacotherapy for outpatients with AGA. Also we evaluated the relationship between therapeutic effect and regular hospital visit. Method: This study was performed retrospectively based on electronic medical record (EMR) data of total 98 patients (topical minoxidil 7% with dutasteride 0.5 mg ($Avodart^{(R)}$) or finasteride 1 mg ($Alopecia^{(R)}$, $Propecia^{(R)}$) with diagnosis of AGA from department of dermatology at a secondary hospital from January $1^{st}$, to May $31^{st}$, 2014. Results: The efficacy and adverse event of topical minoxidil 7%/dutasteride 0.5 mg (DUTA group) were 100% and 45.7%, and of topical minoxidil 7%/finasteride 1 mg (FINA group) were 92.1% and 33.3%, respectively. The mean onset time of responses and adverse events in the FINA group were 3.86 months and 4.43 months. Those in the DUTA group were 3.97 months and 5.06 months. Conclusion: Both FINA and DUTA group were highly effective, but the DUTA group showed higher efficacy and adverse effects than those in the FINA group. Dutasteride may be another alternative in AGA treatment.

• Journal of Animal Reproduction and Biotechnology
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• v.37 no.3
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• pp.209-212
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• 2022

Benign prostatic hyperplasia (BPH) is frequently observed in intact middle-aged or older male dogs with symptoms ranging from asymptomatic to various symptoms such as urination, dyschezia, dysuria, tenesmus, and intermittent serosanguinous or clear serous exudate. A 4-year-old, intact male Welsh corgi with symptoms of intermittent hematuria and serosanguinous exudate at the urethral opening was diagnosed with BPH and intraprostatic hematocyst through ultrasonographic examination and cytology test. The dog was internationally adopted for reproductive purposes and needed to undergo BPH treatment while maintaining fertility. Thus, 2.5 mg finasteride was administered orally once a day for treatment option and therapeutic effects were observed, including loss of clinical symptoms and reduced prostate and intraparenchymal cyst size.

• Journal of Acupuncture Research
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• v.31 no.1
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• pp.95-103
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• 2014

Objectives : The aim of this study is to evaluate the effect of Paljeong-san pharmac-opuncture(PJS) on the rat model of benign prostatic hyperplasia(BPH). Methods : Rats were divided into 5 groups, with 6 rats in each group. The 5 groups included sham-operated group(sham group), BPH model group(BPH group), finasteride-treated group (fina group), PJS-treated groups(PJS 10 and PJS 100 group). Testosterone was injected subcutaneously to the castrated rats except sham group for BPH model. During 4-week experimental period, finasteride(5 mg/kg) was administrated orally once daily in fina group, PJS in PJS 10(10 mg/kg) and PJS 100(100 mg/kg) group and normal saline in sham and BPH group were injected subcutaneously once daily at Jungwan($CV_{12}$). We checked prostate weights, serum concentration of dihydrotestosterone(DHT), morphologic changes of the prostate, and the amount of expression of the proliferating cell nuclear antigen(PCNA) and $5{\alpha}$-reductase gene to evaluate the effect of PJS after 4-week experimental period. Results : 1. PJS and finasteride treatment reduced prostate weights comparing with BPH group, but PJS-treated groups showed no significant changes, unlikely fina group. 2. PJS-treated groups showed significant degreases in concentration of DHT. 3. PJS-treated groups showed significant degreases concentration-dependently in the amount of expression of the PCNA and $5{\alpha}$-reductase gene. 4. PJS treatment showed shrinking of thickness in the prostatic epithelial tissue. Conclusions : PJS has the effects that improve the symptoms of BPH through inhibiting proliferation of the prostatic tissues.