Drug Research Articles

Establishing a multi-method approach for unprecedented detection and quantification of 13 genotoxic impurities (GTIs) in Apixaban drug substance through ultra-performance liquid chromatography (UPLC).

This groundbreaking study introduces a pioneering development of multi-method approach for the first-ever detection and quantification of 13 genotoxic impurities (GTIs) in Apixaban (Apx) drug substance using ultra-performance liquid chromatography (UPLC) with ultraviolet (UV) detector. In this novel endeavor, two distinct UPLC-UV methods, Method A (for impurities A to G) and Method B (for impurities H to M), were meticulously developed and validated as per International Council for Harmonization (ICH) guidelines to address the challenge of identification and control of 13 GTIs in Apx drug substance. The validation process included rigorous assessment of linearity, accuracy, specificity, precision, limit of quantification (LOQ), and limit of detection (LOD) for each impurity in each method which marks a significant advancement in pharmaceutical analysis. The developed methods address the regulatory requirements set forth by ICH M7(R2) guidelines by providing a reliable approach for quantifying GTIs in Apx drug substance at trace levels to minimize the potential carcinogenic risk to the patients.

Antioxidant Properties of Postbiotics: An Overview on the Analysis and Evaluation Methods.

Antioxidants found naturally in foods have a significant effect on preventing several human diseases. However, the use of synthetic antioxidants in studies has raised concerns about their potential link to liver disease and cancer. The findings show that postbiotics have the potential to act as a suitable alternative to chemical antioxidants in the food and pharmaceutical sectors. Postbiotics are bioactive compounds generated by probiotic bacteria as they ferment prebiotic fibers in the gut. These compounds can also be produced from a variety of substrates, including non-prebiotic carbohydrates such as starches and sugars, as well as proteins and organic acids, all of which probiotics utilize during the fermentation process. These are known for their antioxidant, antibacterial, anti-inflammatory, and anti-cancer properties that help improve human health. Various methodologies have been suggested to assess the antioxidant characteristics of postbiotics. While there are several techniques to evaluate the antioxidant properties of foods and their bioactive compounds, the absence of a convenient and uncomplicated method is remarkable. However, cell-based assays have become increasingly important as an intermediate method that bridges the gap between chemical experiments and in vivo research due to the limitations of in vitro and in vivo assays. This review highlights the necessity of transitioning towards more biologically relevant cell-based assays to effectively evaluate the antioxidant activity of postbiotics. These experiments are crucial for assessing the biological efficacy of dietary antioxidants. This review focuses on the latest applications of the Caco-2 cell line in the assessment of cellular antioxidant activity (CAA) and bioavailability. Understanding the impact of processing processes on the biological properties of postbiotic antioxidants can facilitate the development of new food and pharmaceutical products.

Evaluating the Impact of Mini-Competition on Pharmaceutical Procurement: Challenges, Risks, and Regulatory Implications in Indonesia

This study evaluates the impact of the mini-competition method in pharmaceutical procurement in Indonesia, focusing on its challenges, risks, and regulatory implications. Mini-competition, a procurement method designed to promote competitive pricing in e-purchasing, has been introduced to streamline the procurement process, especially for essential goods such as pharmaceuticals. However, this method faces legal and practical challenges, including risks of fraud, reduced competition, collusion, and issues concerning product quality and innovation. The legal framework governing mini competition, including Presidential Regulation No. 12 of 2021, is analyzed to identify potential weaknesses in ensuring transparency and accountability. The research also includes a case study of pharmaceutical product procurement, highlighting the significant price reductions resulting from mini competition but revealing adverse effects on industry sustainability. The analysis of the cost structure of pharmaceutical companies shows that continued price reductions may force companies to cease operations due to unprofitability. Drawing on international case studies, this study concludes that while mini competition can lower procurement costs, it also poses significant risks to product quality, innovation, and market competition. Traditional tender methods are proposed as a more balanced and sustainable approach for pharmaceutical procurement, emphasizing the need for transparent and comprehensive evaluation criteria.

Analyzing the Chiral Purity of Pharmaceuticals: The Application of Cyclodextrin-Based Chiral Selectors in Capillary Electrophoresis

The current review provides a focused analysis of the application of capillary electrophoresis (CE) techniques to determine the chiral purity of pharmaceuticals, with a specific emphasis on cyclodextrin- (CD) based chiral selectors (CSs), highlighting advancements, methodologies, and trends in this area as reported in studies published from 2010 to 2024. The review emphasizes CE’s evolution as a critical tool in this field, discussing its advantages, such as high efficiency, flexibility, relatively low costs, and minimal environmental impact, which make it well-suited for modern pharmaceutical applications. Additionally, it underscores the importance of CE in meeting stringent regulatory requirements for chiral drug substances. A significant shift in method optimization has occurred in the last ten years, shifting from the traditional One-Factor-at-a-Time (OFAT) strategy to the Design-of-Experiments (DoE) approach; this shift has enabled more systematic and robust method development. Furthermore, a common trend in recent years is the application of Quality-by-Design (QbD) principles in method development and optimization, ensuring higher reliability and efficiency. Additionally, there is an increasing focus on developing CE methods capable of detecting both achiral and chiral impurities simultaneously, which enhances the comprehensiveness of the analysis. This review seeks to guide future research and development in optimizing CE methodologies for pharmaceutical applications.

Causal Hierarchy in the Financial Market Network-Uncovered by the Helmholtz-Hodge-Kodaira Decomposition.

Granger causality can uncover the cause-and-effect relationships in financial networks. However, such networks can be convoluted and difficult to interpret, but the Helmholtz-Hodge-Kodaira decomposition can split them into rotational and gradient components which reveal the hierarchy of the Granger causality flow. Using Kenneth French's business sector return time series, it is revealed that during the COVID crisis, precious metals and pharmaceutical products were causal drivers of the financial network. Moreover, the estimated Granger causality network shows a high connectivity during the crisis, which means that the research presented here can be especially useful for understanding crises in the market better by revealing the dominant drivers of crisis dynamics.

Unravelling the shift: exploring consumers’ adoption or resistance of E-Pharmacy through behavioural reasoning theory

In the ever-evolving nature of the healthcare sector, the advent of electronic-Pharmacy introduces a dynamic shift in how consumers acquire and access medical and pharmaceutical products. The research utilized the behaviour reasoning theory. The study evaluated the reasons for adopting and against adopting electronic-Pharmacy. By employing the qualitative approach, this study unravels rich contextual and narrative insights, shedding light on the complexities of individual decision-making processes. The study received responses from 28 through an in-depth interview, and thematic data analysis was employed for the data analysis. The outcome of the research is summarized as follows. The respondents indicated that essential reasons for adopting electronic pharmacy services include convenience and accessibility, prescription management, cost and affordability, logistics, and timely delivery. On the other hand, the reasons against adoption include trust and security concerns, regulatory challenges and legal uncertainties, lack of internet access and privacy concerns. As technology changes healthcare delivery, this research closes the knowledge gap between theory and practice by offering crucial insights into the behavioural aspects influencing electronic-Pharmacy adoption or resistance. The findings are anticipated to significantly impact the academic discourse surrounding electronic-health and the practical implementation of strategies to enhance the integration of electronic-Pharmacy services into conventional healthcare systems.

Chemical Upcycling of Expired Pharmaceuticals as a Source of Value-Added Chemicals for Organic Synthesis and Medicinal Chemistry.

Pharmaceutical and veterinary products are a class of contaminants of emerging concern, and their presence in the environment is due to continuous and incorrect disposal. Environmental scientists have been accumulating data on their adverse effects on animal populations since toxicological effects on wildlife were first published. Therefore, recycling strategies are needed. Valuable active ingredients can be extracted from expired pharmaceuticals and recycled according to various strategies. In an effort to reveal the potential of the chemical upcycling of expired pharmaceuticals, the active ingredients gabapentin and pregabalin were extracted and used as starting materials to prepare a small collection of promising substrates endowed with functionalities and structural three-dimensionality. Gabapentin 1 was transformed into aminoalcohol 3, spiroamine 4, and the bioactive azaspirolactam 5. The lactam analog 6 was synthesized from pregabalin 2. Due to the biological profile of 5 and the structural similarity of the N-alkylated derivatives 5l and 6b with the drug piracetam, a collection of potentially bioactive structural analogs 5a-l and 6a-b were also prepared. Simple extraction, synthesis, and purification procedures were used as a means of chemical and economic revaluation, resulting in moderate to good yields at a low cost.

Acetaminophen production in the edible, filamentous cyanobacterium Arthrospira platensis.

Spirulina is the common name for the edible, nonheterocystous, filamentous cyanobacterium Arthrospira platensis that is grown industrially as a food supplement, animal feedstock, and pigment source. Although there are many applications for engineering this organism, until recently no genetic tools or reproducible transformation methods have been published. While recent work showed the production of a diversity of proteins in A. platensis, including single-domain antibodies for oral delivery, there remains a need for a modular, characterized genetic toolkit. Here, we independently establish a reproducible method for the transformation of A. platensis and engineer this bacterium to produce acetaminophen as proof-of-concept for small molecule production in an edible host. This work opens A. platensis to the wider scientific community for future engineering as a functional food for nutritional enhancement, modification of organoleptic traits, and production of pharmaceuticals for oral delivery.

Regional Approach to Boosting Local Pharmaceutical Manufacturing Capacity: A Critique of the East African Community Pharmaceutical Manufacturing Plan of Action

Abstract The East African Community (EAC) has had a chequered history, evidenced by multiple changes of names and objectives, and a hiatus lasting more than two decades following a collapse in 1977. It was resuscitated in 1999 by its founding members (Uganda, Tanzania, and Kenya). That four other partner states have since joined is a clear testament to the effectiveness of its overhaul. The community is regulated by the EAC Treaty which promotes collective actions in several areas of mutual interests. Plagued by an ongoing access-to-medicines conundrum, EAC governments have considered collective action as recommended by the Treaty. This effort began around the 2010s when policy measures aimed at exploring collective solutions were adopted with a view to replacing reliance on importation and external drug donation with a gradually developed regional pharmaceutical production capacity. EAC policies such as the Policy/Protocol on TRIPS Flexibilities, the Medicines Registration Harmonisation Initiative, the Draft Anti-Counterfeit Policy, and a Pharmaceutical Manufacturing Plan of Action (EAC PMP) have since been developed to achieve this ambitious goal. Using both doctrinal and empirical (semi-structured interviews) methods, this paper examines the EAC PMP – the ‘be all’ of the policies. The priority actions outlined under the plan’s six pillars and presented as a bankable pathway to self-sufficiency in pharmaceutical production are critiqued. The paper finds considerable implementation of the drug harmonisation theme, while the others (leveraging TRIPS flexibilities, ensuring coherence, and boosting research and development and technology transfer) remain largely unimplemented.

Development of Indonesian Original Medicines Study of Standardized Herbal Medicine Products "Antangin JRG" as Traditional Medicine

This study aims to examine the potential for the development of indigenous Indonesian medicines based on traditional medicinal plants. Herbal medicine has been used for generations in Indonesia and has great potential to be developed into more standardized and modern products. This study covers various aspects ranging from product name, content, class, composition, efficacy claims, empirical data, standardization of raw materials, preclinical tests, toxicity tests, to clinical trials. The results of the study show that with proper processing and standardization, Indonesian traditional medicine can compete with modern pharmaceutical products.

Chromosome-level genome assembly of Scathophaga stercoraria provides new insights into the evolutionary adaptations of dung flies

The yellow dung fly Scathophaga stercoraria is a widely distributed species in high-altitude regions of the Northern Hemisphere. It plays important roles as a decomposer, predator, and pollinator in the ecosystem. As a staple model organism, S. stercoraria serves as a standard test species for assessing the toxicity of drug residues in livestock dung and has been the focus of numerous studies. The genetic mechanisms underlying the ecological adaptability of S. stercoraria remain poorly understood. To fill the gap, we first assembled a high-quality chromosome-level genome of S. stercoraria, resulting in a final assembly size of 549.64 Mb, with a contig N50 of 4.06 Mb, and 92.53 % of the sequence anchored to six chromosomes. Gene family analysis revealed an expansion of Toll (Toll1), GNBP3, Cyp303a1, Cyp4d14, Cyp6g1, OR67d, and yolk protein genes in the S. stercoraria genome. Transcriptome analysis indicated that most genes in the trypsin and carboxypeptidase gene families are predominantly expressed during the larval stage, whereas the α-Amylase gene family is mainly expressed during the adult stage. Additionally, PGRP-SC is highly expressed during the larval stage, OBPs are primarily expressed during the adult stage, and yolk protein genes exhibit female-biased expression. Our study not only provides a new resource for the dung flies genomic pool, but also identifies the expression patterns of key ecologically adaptative genes and gene families at the developmental stages, which provides new insights into the ecological adaptive evolution of dung flies.

Impact of Manufacturing Process and Compounding on Properties and Quality of Follow-On GLP-1 Polypeptide Drugs.

The prevalence of follow-on and compounded products of glucagon-like peptide-1 analogs is increasing. We assessed glucagon-like peptide-1 analogs semaglutide and liraglutide for purity, potential immunogenicity, and expected stability, by comparing a representative selection of commercially available follow-on drug substances (DSs) and drug products (DPs) with their corresponding originators. Tests included several chromatography methods coupled with ultraviolet and mass spectrometry detectors, inductively coupled plasma optical emission spectroscopy, inductively coupled plasma mass spectrometry, nuclear magnetic resonance, dissolution analyses, in silico peptide/major histocompatibility complex II-binding prediction, and fibrillation assays. Overall, 16 injectable semaglutide, 8 oral semaglutide, and 2 injectable liraglutide follow-on products were analyzed alongside originator products. Compared with originator, follow-on injectable semaglutide DSs and DPs had new impurities and impurity patterns, including high molecular weight proteins, trace metals, anions, counterions, and residual solvents. Analyses showed that several commercialized follow-on oral semaglutide DPs had a markedly lower quantity of semaglutide than the label claim, while dissolution tests indicated different semaglutide and sodium N-(8-[2-hydroxybenzoyl] amino)caprylate (SNAC) release profiles, which may reduce bioavailability. Neoepitopes were identified in DS and DP semaglutide follow-ons, indicating potential immunogenicity. Fibrillation assays showed increased fibrillation tendency and reduced physical stability in liraglutide follow-on DP samples compared with originator. This study highlights that differences in the manufacturing processes of follow-on semaglutide and liraglutide (vs those used for originators) can result in several changes to the DSs and DPs. The impact of these changes on efficacy and safety outcomes remains unknown and should be investigated by clinical studies.

125 Years of Aspirin: Status of Analytical Methods.

Aspirin, an analgesic, antipyretic and non-steroidal anti-inflammatory drug, was a fascinating discovery that became the precursor to one of the oldest pharmaceutical success stories. It was discovered in 1899 by Felix Hoffman and patented in 1900. In 2024, Aspirin turns 125 years old and is still one of the bestselling medicines today. This review aims to celebrate 125 years of Aspirin and show the status of analytical methods available in the literature to evaluate pharmaceutical products based on Acetylsalicylic Acid (ASA). In addition, it contextualizes them with the current needs of green and clean analytical chemistry. ASA, despite being consolidated in the consumer market, embraces continuous improvement as it is a fundamental part of studies for other new purposes and studies with associations with other active ingredients. In the manuscripts available in the literature, ASA is predominantly evaluated by HPLC (41%) and UV-Vis (41%) methods, which use methanol (21.82%) and acetonitrile (18.18%), followed by buffer (16.36%). The most evaluated pharmaceutical matrix is ASA tablets (40%), followed by ASA tablets in combination with other drugs (26%). While ASA continues to innovate in the market through new forms of delivery and combinations, as well as intended purposes, the analytical methods for evaluating its pharmaceutical products do not. They continue with non-eco-efficient analytical options, which can significantly improve and meet the current demand for green and sustainable analytical chemistry.

Influence of Polymer Film Thickness on Drug Release from Fluidized Bed Coated Pellets and Intended Process and Product Control.

Coated drug pellets enjoy widespread use in hard gelatine capsules. In heterogeneous pellets, the drug substance is layered onto core pellets. Coatings are often applied to generate a retarded release or an enteric coating. In the present study, the thickness of a polymer coating layer on drug pellets was correlated to the drug release kinetics. The question should be answered whether it is possible to stop the coating process when a layer thickness referring to an intended drug release is achieved. Inert pellets were first coated with sodium benzoate and second with different amounts of water insoluble polyacrylate in a fluidized bed apparatus equipped with a Wurster inlet. The whole process was controlled in-line and at-line with process analytical technology by the measurement of the particle size and the layer thickness. The in-vitro sodium benzoate release was investigated, and the data were linearized by different standard models and compared with the polyacrylate layer thickness. With increasing polyacrylate layer thickness the release rate diminishes. The superposition of several processes influencing the release results in release profiles corresponding approximately to first order kinetics. The coating layer thickness corresponds to a determined drug release profile. The manufacturing of coated drug pellets with intended drug release is possible by coating process control and layer thickness measurement. Preliminary investigations are necessary for different formulations.

Aqueous solubility enhancement of theobromine using eco-friendly hydrotropic phenomena

Theobromine, a bioactive compound found in cacao beans, is recognized for its pharmacological health benefits, such as improving heart health by lowering blood pressure, enhancing cognitive function, supporting respiratory health, providing antioxidant benefits, reducing inflammation, and promoting dental health. However, its limited solubility in water poses challenges for therapeutic applications, necessitating methods to enhance its solubility. The approach to enhance its bioavailability making it more effective for medicinal use and easier to incorporate into various pharmaceutical and nutraceutical products. Hydrotropic solubilization, utilizing the amphiphilic nature of sodium benzoate, is employed to improve the solubility of theobromine. Through systematic investigation of varying concentrations (0–3 mol/L) of sodium benzoate and temperature conditions ranging between 303 and 333 K, this study is aimed to elucidate their effects on the solubility of theobromine. Standardized protocols were utilized to measure the concentration of dissolved theobromine in sodium benzoate solutions, while thermodynamic properties were analyzed to understand the underlying mechanism. The study discovered that the solubility of theobromine was enhanced by sevenfold in the presence of sodium benzoate. Thermodynamic analysis revealed the solubilization process to be entropy-driven. Additionally, contact angle estimations confirmed increased hydrophobicity with higher sodium benzoate concentration, facilitating the solubilization of theobromine in the aqueous phase. Furthermore, FTIR analysis indicates that the solubilization of the bioactive compound occurs exclusively subsequent to traversing the minimum hydrotropic concentration (MHC).

Development of an Automated System for Managing the Movement of Pharmaceutical Products in Pharmacies

Development of an Automated System for Managing the Movement of Pharmaceutical Products in Pharmacies

Microalgal Phenolics: Systematic Review with a Focus on Methodological Assessment and Meta-Analysis.

A critical review and analysis of the literature relevant to the phenolic content of eucaryotic microalgae was performed. Several issues were identified and discussed. In summary, the main problems with the reporting on the phenolic content of microalgae are the following: (1) despite its usefulness in the determination of phenolic content in plant samples, the Folin-Ciocalteu assay is non-suitable for microalgal research due to the high presence of interfering compounds in microalgal extracts such as chlorophyll and its derivatives in organic extracts and free aromatic amino acids or nucleotides in aqueous extracts; (2) while there is chromatographic evidence for the presence of simple phenolic acids in most microalgal clades, the lack of critical enzymes of phenolic biosynthesis in most microalgae, as well as the high variability of phenolic profiles even in the same genus, require more extensive research before conclusions are drawn; (3) the accumulation and metabolism of external phenolics by microalgae has been almost universally neglected in studies focusing on the phenolic content of microalgae, even when natural seawater or complex organic media are used in the cultivation process. Despite these issues, the literature focusing on the bioremediation of waste streams rich in phenolics through microalgae demonstrates the ability of those organisms to adsorb, internalize, and in many cases oxidize or transform a wide range of phenolic compounds, even at very high concentrations. Simple phenolics found in waste streams, such as olive mill waste, have been shown to enhance the antioxidant activity and various bioactivities of microalgal extracts, while complex biotransformation products of phenolics have also been characterized. In conclusion, the de novo biosynthesis of phenolic compounds via eucaryotic microalgae requires further investigation with better designed experiments and suitable analytical methods, while the response of microalgae to phenolic compounds in their growth medium is of great practical interest, both in terms of waste treatment and for the production of functional foods, cosmetics, and pharmaceuticals.

Bioreduction of aromatic ketones catalyzed by oak fruits (Quercus Ilex L ) fruit grown in north Algeria

The present work primarily aims to investigate and establish a method for the bioreduction of aromatic ketones to produce corresponding alcohols. This process is crucial for the production of various industrially important chemicals, including pharmaceuticals, agrochemicals, and natural products, and supports the principles of green chemistry. Additionally, this study seeks to valorize the vegetation cover in southern Algeria as a source of biochemical catalysts. Our research focused on the bioreduction of several acetophenone derivatives using the fruits of Oak (Quercus ilex L.) which is cultivated in northern Algeria. The findings indicate that these plant tissues can effectively reduce acetophenone derivatives. Specifically, a chemical yield of approximately 90% was achieved for acetophenone, while yields ranged from 60% to 75% for 4'-haloacetophenones (where X = F, Cl, and Br) and 4'-nitroacetophenone. These results demonstrate that (Quercus ilex L).fruits from northern Algeria can serve as effective biocatalysts in the reduction of aromatic ketones to their corresponding alcohols. This approach not only supports the sustainable production of pharmaceuticals but also provides significant health, environmental, economic, and medical benefits.

A Review on Advancement in Analytical Quality by Design (AQbD)

Analytical Quality by Design (AQbD) represents a transformative methodology in pharmaceutical development, anchored in a systematic, risk-based, and data-driven framework. This approach optimizes analytical methods, fostering heightened product quality, efficient regulatory compliance, and informed decision-making. The industry's increasing acceptance of AQbD principles signifies a paradigm shift towards enhanced efficiency, sustainability, and global harmonization. This review comprehensively explores AQbD principles, regulatory perspectives, and its applications, particularly in analytical method development, including high-performance liquid chromatography (HPLC) and high-performance thin-layer chromatography (HPTLC). Emphasis is placed on the symbiotic relationship between AQbD and analytical method validation (AMV), elucidating their collective role in ensuring reliable and accurate analytical results. Integrating AQbD in method transfer, automation, and control strategies underscores its pivotal role in achieving robust, efficient, and compliant analytical processes. The review delves into lifecycle management and continuous improvement, coupled with AQbD principles, ensuring sustained method reliability throughout the pharmaceutical product lifecycle. AQbD's significant contribution to pharmaceutical lifecycle management, optimization, and change control is explored, emphasizing its systematic, data-driven, and risk-based approach to method development, validation, and ongoing enhancement. This review illuminates AQbD's transformative impact on pharmaceutical analysis, aligning with industry trends toward quality, efficiency, and regulatory compliance.

7886 Impact of Withania somnifera (Ashwagandha) Supplement on Androgen Signalling Pathways

Abstract Disclosure: I.S. Barata: None. J. Yakubu: None. T. Du Toit: None. A.V. Pandey: None. Supplements derived from plant extracts are often used as alternatives to pharmaceutical drugs. These products are often perceived as safe despite the absence of scientific evidence regarding their efficacy and safety and are less strictly regulated than pharmaceutical products. Winter cherry (Withania somnifera, commonly known as ashwagandha) is used as a testosterone booster supplement in multiple countries. Withania somnifera extract was found to increase testosterone and androgen precursors in a small clinical study. However, there is a lack of data regarding effects of Withania somnifera on the steroidogenic pathways. Steroidogenesis impacts not only sexual differentiation, reproduction, and fertility but also other physiological processes, including hypertension and obesity. Moreover, the modulation of hormone signaling is an important target in hormone-responsive pathogenesis, and overproduction of androgens has been implicated in the pathogenesis of prostate cancer (PCa) and polycystic ovarian syndrome (PCOS). In humans, testosterone is mainly produced in the testes after conversion of pregnenolone to 17-hydroxypregnenolone (17-OHPreg) and dehydroepiandrosterone (DHEA, the precursor of androgens) by adrenal CYP17A1, which catalyzes both the 17-hydroxylation of steroids for cortisol production and the breakage of 17,20 bonds (17,20 lyase) in 17-OHPreg to produce DHEA. The intake of substances that may increase androgen levels by people with PCa or PCOS or with predisposition to these conditions may trigger pathogenesis or worsen prognosis by accelerating disease progression. We investigated the effects of Withania somnifera in modulating the adrenal steroidogenic pathway and the possible consequences on the pathogenesis of androgen-responsive conditions, specifically PCa. Adrenal cells were treated with the extract of Withania somnifera to characterize its effect on adrenal steroid profile and CYP17A1 hydroxylase and lyase activities. Prostate cancer proliferation was assessed by direct incubation of prostate cancer cells with extracts as well as with conditioned media from adrenal cells treated for 48h, to simulate natural steroidogenesis. The results suggest that adrenal steroid hormone biosynthesis can be altered by the intake of Withania somnifera extract and that this supplement may affect proliferation of PCa cells. Moreover, the reported testosterone booster effect of Withania somnifera supplementation does not appear to be through increased adrenal androgen production. Presentation: 6/1/2024