Pharmaceuticals最新文献

{"title":"Novel Micro-LC-MS/MS Method for the Quantification of Tenofovir and Its Active Metabolite Tenofovir-Diphosphate in Biological Matrices for Therapeutic Drug Monitoring.","authors":"Isabela Tarcomnicu, Simona Iacob, Valentina Anuta, Emil Neaga, Dan Otelea","doi":"10.3390/ph18060899","DOIUrl":"10.3390/ph18060899","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Sustained drug exposure is a key factor in the treatment of patients infected with human immunodeficiency virus (HIV) or hepatitis B virus (HBV) in order to achieve the intended virological response. Although influenced also by other parameters, adherence to the treatment scheme is the most important for adequate drug exposure. This can be assessed by therapeutic drug monitoring (TDM). Tenofovir (TFV) is a nucleotide analogue used in the treatment of both HIV and HBV. Although various analytical methods for the quantification of tenofovir prodrugs have been published, there is limited literature on methods for simultaneous TFV and its active metabolite, tenofovir diphosphate (TFVDP) direct determination. <b>Methods</b>: In this study, we describe a novel micro-liquid-chromatography-mass spectrometry (micro-LC-MS/MS) method for TDM of TFV and TFVDP in biological matrices (whole blood, plasma). The challenging separation of the high-polarity analytes was resolved on an amino stationary phase, eluted in HILIC (hydrophilic interaction liquid chromatography) mode. The sample preparation included a clean-up step with hexane for the removal of lipophilic compounds and then protein precipitation with organic solvent. <b>Results</b>: The achieved low limits of quantification in blood were 0.25 ng/mL for TFV, and 0.5 ng/mL for TFVDP. Linearity, accuracy (91.63-109.18%), precision (2.48-14.08), and stability were validated for whole blood matrix, meeting the guidelines performance criteria. Samples collected from treated patients were analyzed, with results being in accordance with the reported pharmacokinetics. <b>Conclusions</b>: The new method is adequate for analyzing samples in a clinical set-up. The measurement of both TFV and TFVDP improves clinical decision by an in-depth evaluation of long-term adherence, and together with viral load and resistance data helps guiding the treatment towards the intended virological suppression.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 6","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12195941/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144507729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-Omics and Experimental Validation Reveal Anti-HCC Mechanisms of Tibetan Liuwei Muxiang Pill and Quercetin.","authors":"Wei Chen, Yanzhen Li, Chuting Zhang, Hang Zhou, Jun Ma, Deep K Vaishnani, Bingchi Zeng, Jinglu Yu, Huchao Mao, Jianjian Zheng","doi":"10.3390/ph18060900","DOIUrl":"10.3390/ph18060900","url":null,"abstract":"<p><p><b>Background</b>: Hepatocellular carcinoma (HCC) remains a significant therapeutic challenge due to its complex molecular mechanisms and limited effective treatments. Although the Tibetan medicine Liuwei Muxiang Pill (LWMX) has shown efficacy in gastric and colorectal cancer, no study has yet demonstrated its potential anti-HCC activity. Objective: To evaluate the therapeutic effects of LWMX on HCC. <b>Methods</b>: Integrating network pharmacology, high-resolution mass spectrometry, machine learning, and molecular dynamics simulations, combined with in vitro experiments for mechanism validation. Results: The study identified (Checkpoint kinase 1) CHK1 as a key target of LWMX in HCC regulation and confirmed that quercetin can form a stable complex with CHK1. In vitro experiments demonstrated that LWMX and its active component quercetin significantly inhibit the proliferation and migration of HCC cells. <b>Conclusions</b>: The study establishes CHK1 as a key therapeutic target, confirming the potential of LWMX and its core component quercetin in the treatment of HCC.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 6","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12196418/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144507711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Pharmacogenetic Landscape: Identification of Clinically Relevant Genotypes by a Nation-Wide Medical Testing Laboratory in Romania.","authors":"Cristina Pop, Antoanela Curici, Oliviu Voștinaru, Anamaria Apan, Andra Piciu, Cristina Alina Silaghi, Horatiu Silaghi, Stefan Lucian Popa, Florica Ramona Dorobanțu, Cristina Mogoșan","doi":"10.3390/ph18060898","DOIUrl":"10.3390/ph18060898","url":null,"abstract":"<p><p><b>Background:</b> Pharmacogenetic testing aims to assess the existence of a genetic predisposition that could influence the efficacy or safety of pharmacotherapy. The objective of the present study was to offer a descriptive analysis of the results of the pharmacogenetic tests carried out between 2017 and 2023 within the Synevo laboratories, a provider of medical testing with national expansion. <b>Method:</b> To carry out this analysis, data on the following tests offered by the Synevo laboratories were evaluated: CYP2D6, CYP2C9, CYP2C19, TPMT (thiopurine S-methyltransferase), and factor V Leiden. For each type of test, information was collected on the demographics of the patients tested, as well as the genotyping test result. Data were statistically analyzed and interpreted. <b>Results:</b> In total, 31.453 pharmacogenetic tests were performed in the considered time interval. Most patients for whom pharmacogenetic testing was performed were women (80%), and as for the age range, patients between 31 and 40 years old (45%) and those between 19 and 30 years old (38%) predominated. In the evaluated sample, genetic variants associated with a potential risk of influencing pharmacotherapy could be identified in a proportion of 56% for the CYP2D6 gene, 41% for the CYP2C9 gene, 52% for the CYP2C19 gene, 12% for the TPMT gene, and 16% for factor V Leiden. <b>Conclusions:</b> Pharmacogenetic tests can provide useful information to clinicians in order to personalize pharmacotherapy. Although the interest of medical professionals in these tests is increased, there are currently several impediments to the prescription and routine clinical implementation of pharmacogenetic testing.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 6","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12195894/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144507736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adverse Drug Reactions to SGLT2i Reported by Type 2 Diabetes New Users: An Active Surveillance Study.","authors":"Camelia Bucșa, Ioana Frenț, Ramona Stefan, Adriana Fodor, Georgeta Inceu, Andreea Farcaș, Adriana Rusu, Monica Negovan, Cristina Mogoșan","doi":"10.3390/ph18060904","DOIUrl":"10.3390/ph18060904","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Patients' perspectives on adverse drug reactions (ADRs) may be used to update the safety profile of a drug. We aimed to prospectively follow-up on type 2 diabetes (T2D) patients who were new users of sodium-glucose co-transporter 2 inhibitors (SGLT2i) and to characterize the patient-reported ADRs within routine practice in Romania. <b>Methods</b>: T2D patients from ambulatory settings were interviewed over the phone based on standardized forms, at four time-points across 12 months. We captured the patients' history and auto-medication, as well as any ADR that implied causality to SGLT2i, based on the patient's perspective. <b>Results</b>: In total, 64 patients, with genders being equally represented and with a median age of 59 years (Q1, Q3: 51, 64) were followed-up with. We identified 73 ADRs to SGLT2i that were suspected to be associated with the drug, with an average of 2.35 ADRs per patient (range 0-7 ADRs/patient). The most reported ADR was pollakiuria (7; 9.58%), followed by vulvovaginal candidiasis (6; 8.21%), dysuria (4; 5.47%), and hypoglycemia (4; 5.47%). SGLT2i treatment was interrupted for eight patients. Three (4.10%) ADRs were considered serious as important medical events (hypertensive crisis, angina pectoris, and dyspnea). A positive dechallenge was recorded for 14 ADRs, of which 9 ADRs had a positive rechallenge as well. A probable causality was assessed for 13 of the 73 patient-reported ADRs. <b>Conclusions</b>: Most of the identified ADRs were in line with the known safety profile of SGLT2i. Only three ADRs were serious and unexpected relative to the safety profile, but these had confounding factors that could explain the reactions. Therefore, no new safety concerns related to SGLT2i were determined in this observational study.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 6","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12196258/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144507654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Harnessing the Therapeutic Potential of Pomegranate Peel-Derived Bioactive Compounds in Pancreatic Cancer: A Computational Approach.","authors":"Rita Majhi, Sagar Kurmi, Hilal Tayara, Kil To Chong","doi":"10.3390/ph18060896","DOIUrl":"10.3390/ph18060896","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Pomegranate <i>(Punica granatum)</i> peel, often discarded as waste, contains abundant bioactive compounds such as polyphenols, vitamins, flavonoids, tannins, anthocyanins, and many more. This contributes to remarkable bioactivities, including anticancer, anti-inflammatory, antioxidant, antibacterial, and antifungal properties. Pancreatic cancer is a deadly cancer with a 9% survival rate. Its aggressiveness, invasiveness, quick metastasis, and poor prognosis significantly decrease the survival rate. Thus, we aim to explore pomegranate peel as a possible alternative medication for treating pancreatic cancer through virtual methods. <b>Methods</b>: Firstly, bioactive compounds were collected from multiple databases and screened for oral bioavailability (OB) ≥ 0.3 and drug likeness (DL) ≥ 0.18 scores. Simultaneously, network pharmacology was employed to extract the most probable targets for pancreatic cancer. Further computational analyses were performed, including molecular docking, molecular dynamics simulation, and in silico pharmacokinetics evaluation. <b>Results</b>: Consequently, the top 10 key targets from network analysis were AKT1, IL6, TNF, SRC, STAT3, EGFR, BCL2, HSP90AA1, HIF1A, and PTGS2. However, only AKT1, EGFR, BCL2, HSP90AA1, and PTGS2 exhibited strong binding affinities with pomegranate compounds, which are significantly declared in affected cells to enhance cancer progression. Outcomes from molecular dynamics simulations, particularly RMSD, RMSF, hydrogen bonding, and radius of gyration (Rg), confirmed stable interactions between 1-O-Galloyl-beta-D-glucose, epicatechin, phloridzin, and epicatechin gallate with respective target proteins. <b>Conclusions</b>: This suggests that pomegranate peels hold anticancer bioactive compounds for treating pancreatic cancer. Surprisingly, most compounds adhere to Lipinski's and Pfizer's rules and display no toxicity. However, as this study relies entirely on computational methods, experimental validation is necessary to confirm these findings and assess real-world efficacy and potential side effects.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 6","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12195666/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144507663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Zirconium-89-Oxine Cell Tracking by PET Reveals Preferential Monocyte Recruitment to Cancer and Inflammation over Macrophages.","authors":"Sho Koyasu, Hannah A Minor, Kingsley O Asiedu, Peter L Choyke, Noriko Sato","doi":"10.3390/ph18060897","DOIUrl":"10.3390/ph18060897","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Cell-based therapies have become increasingly important in the treatment of cancers and inflammatory diseases; however, therapies utilizing monocyte-macrophage lineage cells remain relatively underexplored. Non-invasive cell tracking allows a better understanding of the fate of such cells, which is essential for leveraging their therapeutic potential. Here, we employed a Zirconium-89 (⁸⁹Zr)-oxine cell labeling method to compare the trafficking of monocytes and macrophages in vivo. <b>Methods:</b> Mouse bone marrow-derived monocytes and macrophages were each labeled with ⁸⁹Zr-oxine and evaluated for their viability, radioactivity retention, chemotaxis, and phagocytic function in vitro. Labeled cells were intravenously administered to healthy mice and to murine models of granuloma and syngeneic tumors. Cell migration was monitored using microPET/CT, while cell recruitment to the lesions was further assessed via ex vivo biodistribution and flow cytometry. <b>Results:</b> Labeled cells exhibited similar survival and proliferation to unlabeled cells for up to 7 days in culture. While both maintained phagocytic function, monocytes showed higher CCL2-driven chemotaxis compared to macrophages. ⁸⁹Zr-oxine PET revealed initial cell accumulation in the lungs, followed by their homing to the liver and spleen within 2-24 h, persisting through the 5-day observation period. Notably, monocytes trafficked to the liver and spleen more rapidly than macrophages. In both inflammation and cancer models, monocytes demonstrated higher accumulation at the lesion sites compared to macrophages. <b>Conclusions:</b> This study demonstrates the usefulness of ⁸⁹Zr-oxine PET in tracking monocyte-macrophage lineage cells, highlighting their distinct migration patterns and providing insights that could advance monocyte-centered cell therapies.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 6","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12196144/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144507826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multidrug Resistance: Are We Still Afraid of the Big Bad Wolf.","authors":"Abdulelah Alhazza, Adenike Oyegbesan, Emira Bousoik, Hamidreza Montazeri Aliabadi","doi":"10.3390/ph18060895","DOIUrl":"10.3390/ph18060895","url":null,"abstract":"<p><p>After the era of multidrug resistance (MDR) against cytotoxic chemotherapy, the development of resistance against newly developed molecularly targeted drugs also seems inevitable. While the mechanisms involved in resistance against these two categories of anticancer drugs are different, the principles are similar: inherent resistance (also known as primary resistance) is a result of heterogeneity in cancer cells where a subpopulation of the cells do not show a favorable initial response to the drug, while acquired resistance (or secondary resistance), as the name suggests, is developed after repeated treatments due to the plasticity of cancer cells. Despite the introduction of a variety of molecularly targeted drugs to clinical practice, chemotherapy is still at the forefront of the battle against cancer. In this manuscript, we review the major mechanisms involved in MDR and resistance against different categories of molecularly targeted drugs separately, and review some of the strategies studied to overcome the resistance against cancer therapy. While MDR mechanisms have been reviewed previously, the molecular mechanisms of resistance to the latest generations of anticancer drugs are rarely reviewed as a group, and the connection between the two categories of resistance is often missing in this type of publication. Our aim is to illustrate a comprehensive picture of what the landscape of cancer treatment is today with respect to resistance. While this picture seems bleak, and it is the common belief that resistance is inevitable, understanding the mechanisms involved could potentially lead to more efficient approaches to overcoming this so far unbeatable obstacle.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 6","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12196434/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144507710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Defenestration of Liver Sinusoidal Endothelial Cells: The Trigger of Liver Fibrosis.","authors":"Juntao Zhou, Jianqiao Wang, Lijuan Zhang, Chengliang Zhang, Cheng Tian","doi":"10.3390/ph18060893","DOIUrl":"10.3390/ph18060893","url":null,"abstract":"<p><p>Liver fibrosis is a common pathological manifestation of various chronic liver diseases, distinguished by the excessive accumulation of the extracellular matrix. If unresolved, liver fibrosis can progress to cirrhosis or hepatocellular carcinoma. Fenestrae are important structures of liver sinusoidal endothelial cells (LSECs) regulating hepatic substance exchange, immune response and hemodynamics. The loss of this structure is usually accompanied by dysfunction of LSECs, which disrupts normal liver physiology by impairing hepatic substance exchange, compromising liver microcirculation, and activating hepatic stellate cells (HSCs). This cascade of events ultimately contributes to the onset and development of liver fibrosis. Oxidative stress, impairment of the NO signaling pathway, actin-myosin complex remodeling and pathological angiogenesis are considered to be the main mechanisms underlying LSEC defenestration. Recently, research on the treatment of LSEC defenestration has made notable progress, and findings suggest a potential value in the application of anti-fibrotic therapies. This article expounds the important correlation between defenestration of LSECs and liver fibrosis, while also reviews therapeutic agents and approaches targeting this pathological process.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 6","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12196518/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144507684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential Target Receptors for the Pharmacotherapy of Burning Mouth Syndrome.","authors":"Takahiko Nagamine","doi":"10.3390/ph18060894","DOIUrl":"10.3390/ph18060894","url":null,"abstract":"<p><p><b>Objective:</b>Burning mouth syndrome (BMS) is a chronic, intractable orofacial pain condition characterized by a burning sensation in the oral mucosa without discernible lesions. The syndrome predominantly affects menopausal and postmenopausal women and is considered a form of nociplastic pain, where the processing of pain stimuli is altered. Given the significant sex disparity, it is crucial to consider underlying neurobiological differences that may inform treatment. This review explores potential pharmacological targets by examining the pathological mechanisms of BMS. <b>Method of Research</b>: A narrative review approach was utilized to systematically explore and synthesize literature regarding the pathophysiology of BMS and to identify receptors implicated in the enhancement of sensory transmission and the altered processing of pain stimuli. <b>Results</b>: The mechanism of enhanced sensory transmission points to receptors such as TRPV1, P2X3, and CB2 as potential targets. However, considering the nociplastic nature of BMS and its prevalence in women, mechanisms involving altered central pain processing are paramount. Research indicates significant sex differences in glutamate transmission and plasticity within reward-related brain regions. This suggests that the N-methyl-D-aspartate (NMDA) receptor, a cornerstone of glutamate signaling and synaptic plasticity, is a primary therapeutic target. Furthermore, the altered processing of pain and reward, which is a key feature of chronic pain, implicates the brain's dopaminergic system. A decrease in dopamine D2 receptor function within this system is believed to contribute to the pathology of BMS. Estrogen receptors are also considered relevant due to the menopausal onset. <b>Conclusions</b>: Based on the evidence, the most promising targets for pharmacotherapy in BMS are likely the NMDA receptor and the dopamine D2 receptor. The high prevalence of BMS in women, coupled with known sex differences in the glutamate and dopamine pathways of the reward system, provides a strong rationale for this focus. Effective treatment strategies should therefore aim to modulate these specific systems, directly or indirectly controlling NMDE receptor hyperactivity and addressing the decreased D2 receptor function. Further research into therapies that specifically target this sex-linked neurobiology is essential for developing effective pharmacotherapy for BMS.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 6","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12196080/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144507759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of <i>CYP1A2</i>, <i>CYP2D6</i>, and <i>CYP3A4</i> Variation on Antipsychotic Treatment Outcomes.","authors":"Lauren Varney, Stephen Murtough, Marius Cotic, Rosemary Abidoph, Lian Chan, Noushin Saadullah Khani, Alvin Richards-Belle, Maria Richards-Brown, Daisy Mills, Daniele Panconesi, Yogita Dawda, Parveen Sharma, Chetan Shah, Agostina Secchi, Ramin Nilforooshan, Santosh Mudholkar, Rosie Murdoch, Jazmin Molai, Rebecca Griffiths, Suruthy Senthilkumar, Helen Blake, Steve Lankshear, Jennifer McRoberts, Bethany Pastor, Carmel Thomas, Sabrina Richards, Alison Welfare-Wilson, Sai-Bo Cheung, Rebecca Cox, Anita Chinazam Jibero, Reanne Anad, Rebeka Laczik, Sharif Ghali, Alex J Berry, Joanna Curwen, Koye Odutoye, Girija Kottalgi, Sally Williams, Solomon Wong, Nithya Anandan, Georgy Pius, Tonye Ajiteru, Victoria Clark, Philip van Driel, Amir Bashir, Samantha Court, Minerva Pawsey, Anna Skowronska, Jessica Woodley, Elvira Bramon","doi":"10.3390/ph18060892","DOIUrl":"10.3390/ph18060892","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Antipsychotic treatment response varies considerably between individuals, with one potential reason being genetic variation affecting the cytochrome P450 enzymes that metabolise them. <b>Methods</b>: With a diverse sample of 453 participants, we studied the influence of <i>CYP1A2</i>, <i>CYP2D6</i>, and <i>CYP3A4</i> variation on three antipsychotic treatment outcomes: participant-reported adverse antipsychotic drug reactions, health-related quality of life, and the dose of antipsychotic medication prescribed. These measures were taken from the baseline assessment, before a pharmacogenetic intervention was delivered. <b>Results</b>: Over half of our sample (62.9%) were carriers of an allele associated with altered metabolism of antipsychotic medications on <i>CYP2D6</i> or <i>CYP3A4</i>, the two genes with pharmacogenetic guidelines for antipsychotic medications. Ultrarapid CYP2D6 metabolisers reported significantly lower levels of adverse antipsychotic drug reactions than normal CYP2D6 metabolisers (mean difference: -11.1; 95% confidence interval [CI]: -18.9, -3.3; <i>p</i> = 0.00575). There was also suggestive evidence of lower quality of life scores in those carrying one (mean difference: -0.0863; 95% CI: -0.1806, 0.0081; <i>p</i> = 0.0731) or two copies (mean difference: -0.0803; 95% CI: -0.1734, 0.0129; <i>p</i> = 0.0914) of the <i>CYP1A2*30</i>-inducible allele. <b>Conclusions</b>: Our findings suggest that even when looking at a small number of cytochrome P450 genes, carrying an allele associated with altered antipsychotic medication metabolism is relatively common. We also found evidence that the CYP genotype can influence antipsychotic treatment outcomes, specifically adverse drug reactions and quality of life scores.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"18 6","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12196257/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144507703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}