Prostate cancer is the most common cancer in men. While active surveillance is now routinely offered to men with early-stage prostate cancer, almost 50% will eventually require definitive therapy, like radiation or prostatectomy, which carry significant genitourinary side effects. Systemic antiandrogen therapy have approved for locally-advanced and metatatic prostate cancer, but their substantial metabolic, sexual, and cardiovascular side effects have precluded its use for early-stage disease or prevention. Localized sustained release of an anti-androgen via a drug-delivering implant could provide long-term, prostate-specific delivery of anti-androgens while avoiding systemic toxicity. Biolen®, is a silicone-based bicalutamide implant with the ability to deliver sustained bicalutamide levels to the prostate for more than 2 years. In IND enabling canine studies, we observed therapeutic intraprostatic levels with minimal systemic exposure and no off-target toxicities. Prostate bicalutamide levels were similar to oral bicalutamide but with nearly 1000-fold lower systemic plasma bicalutamide levels. Implants caused no fibrotic encapsulation, inflammation or local tissue toxicity. A phase I pre-surgical trial in men with localized prostate cancer confirmed high therapeutic prostate levels with very low systemic exposure. These results support exploration of this approach in early-stage prostate cancer, benign prostate hyperplasia, and other settings that would benefit from sustained organ-selective drug delivery.

The increasing occurrence of pharmaceutical residues in biological and environmental matrices has created a demand for sensitive, selective, and sustainable analytical methods for their determination. Letrozole (LTR) and bicalutamide (BCL), two non-steroidal anticancer drugs co-administered for the treatment of testotoxicosis, exhibit native fluorescence; however, their emission spectra significantly overlap, preventing their direct simultaneous determination. In this work, a green synchronous spectrofluorimetric method was developed to overcome this limitation by improving spectral resolution through synchronous scanning of the excitation and emission monochromators. Under the optimized conditions (Δλ = 50 nm), LTR and BCL were directly quantified at 240 and 272 nm, respectively, without prior separation or derivatization. The proposed method showed linear responses over concentration ranges of 0.5-150.0 ng mL[-1] for LTR and 5.0-1000.0 ng mL[-1] for BCL, with limits of detection of 0.09 and 1.29 ng mL[-1], respectively. The method was validated according to ICH guidelines and demonstrated satisfactory accuracy, precision, selectivity, and reproducible analytical performance. Its applicability was confirmed by the simultaneous determination of both analytes in pharmaceutical formulations, spiked human plasma and urine, and environmental water samples, providing satisfactory recoveries with minimal matrix interference. In addition, the method requires minimal solvent consumption and avoids hazardous reagents, and its environmental sustainability was confirmed using the Analytical Green Star Area (AGSA) and Multi-color Assessment (MA) tools.

Cefmetazole (CMZ), a cephamycin, has a protein-binding rate of approximately 85%. The unbound concentration is microbiologically active and may vary greatly depending on variations in human serum albumin (HSA) concentration. However, the binding parameters and sites of HSA have not been clarified, and the predicted unbound concentrations using these parameters have not been evaluated. This study aimed to clarify these binding characteristics and evaluate unbound CMZ concentrations predicted using the calculated binding parameters. Total and unbound CMZ concentrations in the HSA solutions were measured at several HSA concentrations (10 g/L, 25 g/L, and 40 g/L) and total CMZ concentrations (10, 60, and 150 mg/L). A Scatchard plot was constructed. To identify specific binding sites, competitive binding assays were performed using the site markers warfarin, dansylsarcosine, bicalutamide, and bilirubin. Unbound CMZ concentrations were predicted using binding parameters from total CMZ and albumin concentrations in 37 patients. The association constant (K) for CMZ to HSA was determined to be 6.59 × 10[3] M[-1], with number of binding sites (n) of 1.08. The binding rate decreased as the CMZ concentration increased or the HSA concentration decreased. Competitive binding assays revealed that CMZ binds to Subdomain IB on HSA. A strong correlation (r=0.907) was observed between predicted and measured unbound CMZ concentrations. This study successfully defined the binding parameters and specific binding sites of CMZ on HSA, and unbound CMZ concentrations were accurately predicted from the total CMZ concentrations in clinical patients using these binding parameters.

Androgenetic alopecia (AGA) is the most common cause of non-scarring hair loss in men. Although topical minoxidil and oral finasteride are established treatments, some patients show limited clinical response despite prolonged therapy. Evidence on the use of oral bicalutamide in male AGA remains scarce because of concerns about systemic adverse effects. We report the case of a 45-year-old man with treatment-resistant AGA who experienced clinically apparent hair regrowth during oral bicalutamide exposure after an inadequate response to conventional therapies. Treatment was accompanied by gynecomastia, mastodynia, decreased libido, erectile dysfunction, and mild elevations in hepatic enzymes, leading to drug discontinuation. Clinical adverse effects resolved after withdrawal of bicalutamide; however, follow-up hormonal evaluation and liver function tests were unavailable. This case describes a temporal association between androgen receptor blockade, clinically apparent hair regrowth, and clinically significant adverse effects. Although the findings provide additional insight into the role of androgen receptor signaling in AGA, they should not be interpreted as evidence supporting the use of oral bicalutamide in male patients. Further controlled studies are needed to better define the safety profile and potential role of androgen receptor antagonism in androgenetic alopecia.

Enzalutamide, a second-generation androgen receptor inhibitor (SGARI) for prostate cancer, is associated with rare but severe pulmonary toxicities. While typically manifesting as drug-induced interstitial lung disease (DI-ILD), these agents can also trigger acute exacerbation or rapid progression of pre-existing interstitial lung abnormalities (ILA). We report the case of an 83-year-old man with baseline ILA and emphysema who had previously undergone a laparoscopic radical prostatectomy. He maintained stable respiratory symptoms on bicalutamide for four years but developed progressive dyspnea within one month of switching to enzalutamide for biochemical recurrence. However, a chest computed tomography (CT) scan was not performed promptly upon symptom deterioration. This missed opportunity for early radiologic evaluation resulted in a 10-month diagnostic delay. Following the immediate discontinuation of enzalutamide and the concurrent initiation of nintedanib, the patient achieved radiologic stability and demonstrated improved exercise tolerance at the 6-month follow-up. From the patient's perspective, the rapid progression of dyspnea was highly distressing, but he expressed significant relief and satisfaction with the improvement in his exercise tolerance following the medication adjustment. This clinical course highlights that prompt withdrawal of the offending agent is paramount, while phenotype-driven antifibrotic therapy may serve as a potential supportive intervention once irreversible fibrosis is established.

Emerging pathogens such as SARS-CoV-2 are always the cause of extremely high morbidity and mortality. Despite a shared history with humanity spanning more than half a decade, COVID-19 treatment is still challenging, especially in people with comorbidities. The RBD of the S-glycoprotein is a promising target because it plays a key role in the tropism of SARS-CoV-2. Using AutoDock Vina together with a bash script FDA-approved compounds were virtually screened for their binding affinity to the RBD pocket, which was identified in our previous work. Nine promising compounds were selected based on the noncovalent interaction pattern and were studied by short molecular dynamics simulation. Bicalutamide and ketodarolutamide formed sufficiently stable complexes and were studied by longer molecular dynamics. Ketodarolutamide was the only ligand whose parameters had acceptable values for a potential RBD inhibitor. A characteristic component of both compounds was halogenated benzonitrile, which in the case of ketodarolutamide stabilized the complex. Further ELISA also partially confirmed the inhibitory effect of ketodarolutamide on the RBD/hACE2 interaction, which is consistent with known reports of a milder course of COVID-19 in patients on antiandrogen therapy. We suggest that ketodarolutamide can be considered as a promising scaffold for the development of a benzonitrile-containing RBD inhibitor.