A Stability Indicating UPLC Method for Finasteride and Its Related Impurities

The objective of the present research work is to develop a gradient, reversed-phase liquid chromatographic (RP-UPLC) method for the determination of Finasteride in pharmaceutical bulk drugs for assay and its related impurities. The chromatographic separation was achieved on a Waters ACQUITY UPLC BEH Phenyl Column (150 mm × 2.1 mm, 1.7 μm), The gradient LC method employs solutions A and B as mobile phase. The solution A Contains 2.5 mM ortho phosphoric acid (Buffer) and solution B contains a mixture of acetonitrile and water in the ratio of (90:10 v/v). The flow rate was 0.22 ml/min and the detection wavelength was 210 nm. In the developed UPLC method, the resolution between Finasteride and its potential impurities, namely Imp-1, Imp-2, Imp-3 and Imp-4 was found to be greater than 2.0. The drug was subjected to stress conditions of hydrolysis, oxidation, photolysis and thermal degradation. Considerable degradation was found to occur in alkaline medium and oxidative stress conditions. Degradation product formed during oxidative hydrolysis was found to be Imp-1. The stress samples were assayed against a qualified reference standard and the mass balance was found close to 99.5%. The developed RP-UPLC method was validated with respect to linearity, accuracy, precision and robustness. The limit of quantification of Imp-1, Imp-2, Imp-3 and Imp-4 were 0.06, 0.06, 0.05 and 0.036% (of analyte concentration, i.e. 0.5 mg/ml) with 1μl injection volume. The developed method was found to be linear in the range of 2.5 - 15 μg/mL with correlation coefficient of 0.999 for assay procedures and found to be linear in the range of 0.05 - 3 μg/mL with correlation coefficient of 0.999 for related impurities.

用国际勃起功能指数评价口服Finasteride药物对男性脱发患者性功能的影响

Objective: To evaluate variations in sexual and erectile function in subjects taking 1 mg of finasteride for androgenetic alopecia by administering the abridged 5-item version of the International Index of Erectile Function (IIEF-5) questionnaire before and during treatment. Design: In a multicenter study, 186 patientswith androgenetic alopeciawere asked to complete the IIEF-5 regarding the domain of erectile function before (at baseline) and 4 to 6 months after beginning finasteride treatment. The test was self-administered. Setting: The study was conducted in 7 institutional dermatology departments in Italy (Bologna, Rome, Genoa, Cagliari, Milan, Florence, and Bari). Patients: A total of 186 patients with androgenetic alopecia were evaluated before and 4 to 6 months after the initiation of finasteride therapy (1 mg). All patients (age range, 19-43 years; mean age, 28.3 years) were followed up as outpatients. Results: The score on each of the 5 domains of the IIEF-5 did not showany significant change after 4 to 6months of treatment. Conclusions: Our results support the clinical impression that sexual side effects are actually much less common than reported in clinical trials. The sexual function of all patients remained stable during treatment with 1 mg of finasteride.

Screening and confirmation methods of the major urinary metabolite of finasteride–carboxy-finasteride by liquid chromatography–mass spectrometry and liquid chromatography–tandem mass spectrometry

Screening and confirmation methods of the major urinary metabolite of finasteride–carboxy-finasteride for doping control purpose were developed.Liquid–liquid extraction was adopted for the sample preparation.Analytes were detected by positive electrospray ionization in single quadrupole and triple quadrupole mass spectrometer.In the screening method,selected ion monitoring(SIM)mode was used to monitor m/z 403 for carboxy-finasteride.In the confirmation method,product ion mode was used to monitor the precursor ion m/z 403.The limit of detection was below 2 ng/mL for the screening method.Good linearity was obtained in the range 10.0–500.0 ng/mL.The intra-run and inter-run precision calculated from quality control(QC)samples was less than 5.3%.The accuracy as determined from QC samples was within ±6.6%.The screening method was applied for the analysis of excretion samples,allowing the detection of carboxy-finasteride for up to 49 h in urine specimen collected after an oral administration of 5 mg of finasteride.

The corpus cavernosum after treatment with dutasteride or finasteride： a histomorphometric study in a benign prostatic hyperplasia rodent model

Erectile dysfunction is a common side effect of finasteride and dutasteride treatments. The objective of this study was to investigate the structural changes in the penis using a benign prostatic hyperplasia （BPH） rodent model treated with dutasteride or finasteride. Sixty male rats were divided into the following groups： C, untreated control rats; C ＋ D, control rats receiving dutasteride; C ＋ F, control rats receiving finasteride; H, untreated spontaneously hypertensive rats （SHRs）; H ＋ D, SHRs treated with dutasteride; and H ＋ F, SHRs treated with finasteride. Treatments were performed for 40 days, and penises were collected immediately thereafter. The organs were analyzed using histomorphometric methods to determine the cross-sectional penile area, as well as the surface density （Sv） of smooth muscle fibers, connective tissue, elastic system fibers, and sinusoidal spaces of the corpus cavernosum. The results were compared using a one-way ANOVA with Bonferroni＇s posttest. Groups C ＋ D and C ＋ F had a significantly smaller penile cross-sectional area, but more elastic system fiber Sv compared to Group C. Group C ＋ D showed less smooth muscle Sv, and Group H showed more connective tissue but a smaller sinusoidal space Sv in the corpus cavernosum compared to Group C. Groups H ＋ D and H ＋ F had less smooth muscle Sv than Group H. Group H ＋ D also had more connective tissue and elastic system fiber Sv than Group H. Both dutasteride and finasteride promoted penile modifications in the control rat penis, although this affect was ~reater in Group H animals. In this rodent model, dutasteride was the drug that most affected the corpus cavernosum.

The intriguing role of fibroblasts and c-Jun in the chemopreventive and therapeutic effect of finasteride on xenograft models of prostate cancer

In a large clinical trial, finasteride reduced the rate of low-grade prostate cancer （PCa） while increasing the incidence of high-grade cancer. Whether finasteride promotes the development of high-grade tumors remains controversial. We demonstrated the role of fibroblasts and c-Jun in chemopreventive and therapeutic effect of finasteride on xenograft models of PCa. LNCaP （PC3） cells or recombinants of cancer cells and fibroblasts were implanted in male athymic nude mice treated with finasteride. Tumor growth, cell proliferation, apoptosis, p-Akt, and p-ERKI/2 were evaluated. In LNCaP （PC3） mono-grafted models, finasteride did not change the tumor growth. In recombinant-grafted models, fibroblasts and c-Jun promoted tumor growth; finasteride induced proliferation of LNCaP cells and repressed PC3 cell apoptosis. When c-Jun was knocked out, flbroblasts and/or finasteride did not promote the tumor growth. Finasteride inhibited p-Akt and p-ERKI/2 in mono-culture cancer cells while stimulating the same signaling molecules in the presence of fibroblasts. Reduced p-Akt and p-ERKI/2 were noted in the presence of c-Jun-I- fibroblasts. Fibroblasts and c-Jun promote PCa growth; finasteride further stimulates tumor growth with promoted proliferation, repressed apoptosis, and up-regulated pro-proliferative molecular pathway in the presence of fibroblasts and c-Jun. Stromal-epithelial interactions play critical roles in finasteride＇s therapeutic effects on PCa. Our findings have preliminary implications in using finasteride as a chemopreventive or therapeutic agent for PCa patients.

Controlled clinical trial for evaluation of hair growth with low dose cyclical nutrition therapy in men and women without the use of finasteride

Aim: To evaluate possible results with the stimulation use of minoxidil and the strengthening of hair roots with nutritional cyclical supplements, resulting in increased hair regrowth, without the use of anti androgens and enzyme blockers. Methods: This prospective controlled clinical trial compares the current acknowledged form of treatment for hair loss within two controlled groups for both men and women against the use of cyclical nutritional therapy and minoxidil 2%. One hundred patients in each of the 4 groups, a total of 400 patients, were followed for 1 year. The progress was evaluated every 2 months with computerised measurements of hair density, hair calibre, global photography and uniquely designed self-assessment scores. Results: The use of nutritional supplements showed consistent improvements in both treatment groups of men and women against the controlled groups with a correction of hair fall and minimum 18% increased density within 2 months with further improvement to a maximum of 156% over 1 year. Conclusion: Hair loss occurs when weak, sensitive, follicles are affected by multiple causes. Hair regrowth can be achieved consistently and safely by strengthening the hair roots and promoting hair growth without necessarily depending on the use of anti androgens.

Sub-chronic effects of a Phthirusa pyrifolia aqueous extract on reproductive function and comparative hormone levels in male rats

Objective: To explore the effects of aqueous extract from Phthirusa pyrifolia leaves(67 mg/kg body weight for 12 days) on the reproductive function of male Wistar rats through oral administration.Methods: Animals(n = 30), aged 13 weeks and weighing(378.5 ± 5.0) g, were housed in a vivarium under controlled environmental conditions [photoperiod of 12 h light/dark,temperature of(23 ± 1)C] and were fed standard rations ad libitum. The experiment ran for 12 days, wherein animals were divided into three groups: negative control(n = 6)received water, positive control(n = 12) with finasteride at a concentration of 1.0 mg/kg;and a test group(n = 12) submitted to aqueous extract. At the end of the experiment, the animals were sacrificed and submitted to analyses.Results: The morphological results of the testes showed that the aqueous extract induced significant changes in the diameter and cross-sectional area of the seminiferous tubules as well as the thickness of the seminiferous epithelium. Furthermore, the extract was able to abruptly decrease testosterone concentrations by about 81.88% in the treated group when compared with the negative control,(47.0 ± 4.8) ng/d L and(255.0 ± 2.0) ng/d L,respectively, and 76.8%,(211.0 ± 8.7) ng/d L, when compared with finasteride. However,the extract causes neither liver damage nor impairment of renal function.Conclusions: These results suggest that the high amounts of flavonoids shown to be in the extract may be responsible for its hepato-protective effects and suggest a possible decrease in the libido and reproduction of rats.

治疗男性秃顶药物可能损伤生殖能力

据美国国家科学院院报（PNAS）网站（2013-09-12）报道，药物Finasteride过去被核准用以治疗良性前列腺肿大（BPH），但15年前适应证增加治疗男性秃顶用途，近年来已越来越多有秃顶困扰的男性会低剂量服用此药。日前一份加拿大研究发现，有生育问题的男性停止使用Finasteride后，精子数量出现明显上升，显示使用该药物会伤害男性生育能力。

青光眼药贝美前列素可能用于治疗男性脱发

资料来源：The FASEB Journal发布时间：2012.10.30男性秃发通常是遗传性的,在美国估计有4000万人受此困扰。男性秃发的主要原因之一是雄性激素双氢睾酮（DHT）水平升高,一种名为5-α还原酶的酶可促进DHT生成。美国FDA目前批准的可用于治疗男性秃发的有两种药物：默克制药的Finasteride（非那雄胺）和强生公司的Minoxidil（5%米诺地尔溶液）,它们均通过抑制5-α还原酶,进而防止DHT生成。

良性前列腺增生症的药物治疗

前列腺增生症(BPH)是中老年人常见病之一,发病率50岁为40％,60岁为70％,70岁为70％,80岁以上为90％。手术治疗效果较好,但对病人造成不同程度的损害。

Bawu Decoction(八物汤) Ameliorates Benign Prostatic Hyperplasia in Rats

Objective：To evaluate the efficacy of Bawu Decoction（八物汤,BWD,Palmul-tang in Korean）against benign prostatic hyperplasia（BPH）.Methods：Twenty-four male Wistar rats were divided into 4 groups,with 6 rats in each group.The 4 study groups included sham-operated group（CON）,BPH model group,finasteride-treated group,and BWD-treated group.All the groups except CON group received a subcutaneous injection of 10 mg/kg of testosterone,while CON group received saline.Finasteride at a dose of 5 mg/kg was administered to the finasteride-treated group for a period of 4 weeks.BWD group received BWD at a dose of 200 mg/kg for 4 weeks.The prostatic weight,prostate weight to body weight ratio,relative prostate weight ratio,serum testosterone and dihydrotestosterone（DHT）level,and histological analysis of prostatic tissue were analyzed.Results：Compared to BPH model group,BWD administration was associated with reductions in prostatic weight,prostate and relative prostate weight ratio weight to body weight ratio（P〈0.05）.The concentration of serum testosterone and DHT were higher in BPH group compared with CON group（P〈0.05）.Administration of finasteride and BWD suppressed the elevation of serum testosterone and DHT levels significantly（both P〈0.05）.In addition,BWD suppressed the growth of prostatic tissue（P〈0.05）.Conclusion：BWD has suppressant effects on development of BPH through inhibition of serum testosterone and DHT.