Expert Review of Clinical Pharmacology最新文献

Introduction: Non - clear cell renal cell carcinoma (nccRCC) encompasses a heterogeneous group of rare malignancies, representing approximately 20-25% of all renal cancers. Unlike clear cell RCC (ccRCC), these subtypes - papillary, chromophobe, collecting duct, translocation, molecularly defined variants and others - display distinct biological behaviors, genetic profiles, and therapeutic sensitivities, which preclude a uniform treatment approach.

Areas covered: This review provides an updated overview of systemic therapy for nccRCC, integrating evidence from prospective trials, retrospective series, and translational research. For most of these histologies, immune checkpoint inhibitor (ICI) - based combinations (e.g. pembrolizumab - lenvatinib, nivolumab - cabozantinib or nivolumab-ipilimumab) have demonstrated the best activity. In chromophobe RCC (chRCC), also mechanistic target of rapamycin (mTOR) inhibition appears particularly relevant, whereas in collecting duct carcinoma and renal medullary carcinoma platinum-based chemotherapy continue to have an important role, with cabozantinib showing encouraging results. Novel biomarker-driven approaches are emerging for selected molecular subsets.

Expert opinion: Although remarkable progress has been achieved, the optimal therapeutic strategy for nccRCC remains undefined. Future efforts should focus on histology- and biomarker-driven clinical trials, molecular stratification, to optimize efficacy across subtypes. International collaboration is crucial to overcome the challenges posed by the rarity and biological heterogeneity of these tumors.

Introduction: In patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI), long-term dual antiplatelet therapy (DAPT) is the current standard of care. However, recent evidence suggests that shortening DAPT duration in favor of single antiplatelet therapy (SAPT) can optimize the overall clinical benefit, as it can prevent bleeding without significant tradeoff in ischemic events.

Areas covered: In this narrative review, we synthesize current evidence from PubMed and SCOPUS on SAPT vs DAPT regimens in CAD patients undergoing PCI, including pharmacodynamic and clinical outcomes data, and we propose an algorithm for appropriate antiplatelet regimen selection depending on the ischemic and bleeding risk profile of the individual patient.

Expert opinion: The landscape of antiplatelet treatment regimens has significantly evolved over time, with the current trend being toward a tailored approach based on risk profile, aiming to reduce the risk of bleeding while maintaining ischemic protection. The accurate evaluation of each patient's ischemic and bleeding risk profile is of utmost importance. Dedicated tools have been developed to optimize patient risk profiling and help guide the selection of the antiplatelet regimen. Based on risk estimation, several strategies can be used to reduce the overall risk, including the selection and duration of the antiplatelet regimen.

Background: Dual antiplatelet therapy with aspirin and P2Y12 inhibitors is the first antiplatelet of choice for acute myocardial infarction (AMI), but alternatives are needed for patients at high bleeding risk or with aspirin intolerance/hypersensitivity. This observational study investigated the efficacy and safety of indobufen, a reversible COX-1 inhibitor, among AMI patients compared to those receiving aspirin.

Methods: We retrospectively enrolled 907 consecutive AMI patients treated between June 2021 and June 2024. The primary endpoints were GUSTO bleeding and MACE between aspirin and indobufen.

Results: Patients receiving indobufen were older and had higher rates of comorbidities such as type 2 diabetes, gastritis, and peptic ulcers (all p < 0.05). Over a median follow-up of 462 days, aspirin was associated with a higher incidence of GUSTO mild bleeding (23.8% vs. 8.6%, p < 0.001), with no significant differences in moderate/severe bleeding, re-infarction, stroke, heart failure, rehospitalization, or MACE (all p > 0.05). Multivariate regression confirmed indobufen independently reduced GUSTO mild bleeding risk. Boruta and SHAP analyses identified antiplatelet therapy, particularly aspirin, as a predictor of GUSTO mild bleeding.

Conclusions: Indobufen may be considered an alternative antiplatelet therapy for AMI patients with a high bleeding risk and/or aspirin intolerance/hypersensitivity, however, prospective studies are needed to confirm these findings.

Introduction: Medicine-related harm associated with polypharmacy is a pertinent global health challenge. Deprescribing (reducing or stopping) medicines that cause more potential harm than benefit could mitigate the risk of medicine-related harm. However, the existing deprescribing research-to-practice gap threatens the long-term sustainability and scalability of deprescribing efforts.

Research design and methods: To address this, key stakeholders including healthcare practitioners, academics, policymakers and representatives of peak professional organizations, gathered at a World Café workshop to reflect on progress achieved in the deprescribing research and practice landscape while exploring the top future priorities for deprescribing.

Results: Thirty participants agreed on three top priorities: improving the clinical management of deprescribing; engaging consumers and gaining their perspectives; and raising awareness to enhance communication. Emerging themes and related barriers and catalysts were derived and mapped to a socio-ecological model offering a bird-eye's view of these factors on an individual, interpersonal, organizational, and societal level.

Conclusions: Our World Cafe' highlights opportunities for future deprescribing research and practice. To promote the uptake of deprescribing in practice, catalysts could include leveraging new technology, promoting deprescribing via social media and optimizing workforce staff and knowledge. Ultimately, this knowledge may motivate deprescribing efforts and bridge the research-to-practice gap.

Introduction: Traditional therapeutic drug monitoring (TDM) faces limitations in accuracy and adaptability, often failing to optimize therapy for complex patients. Machine learning (ML) is emerging as a powerful tool to overcome these challenges, offering a data-driven paradigm to enhance therapeutic outcomes and minimize toxicity for drugs with narrow therapeutic indices.

Areas covered: This review synthesizes the evolution of ML in TDM. We cover foundational models that predict drug exposure from sparse data using either real-world or simulation-based training. We then explore the extension of these techniques to proactive first-dose optimization and the recent development of hybrid models, which integrate the physiological interpretability of population pharmacokinetic frameworks with the corrective power of ML.

Expert opinion: The future of TDM lies not in replacing mechanistic models, but in their convergence with ML. While promising, clinical translation requires overcoming critical barriers in data access, model interpretability, and workflow integration. The long-term trajectory points toward dynamic Digital Twins capable of forecasting patient-specific benefit-risk profiles. Ultimately, validated hybrid tools embedded in clinical decision support systems could establish proactive, individualized dosing as the new standard of care in personalized pharmacotherapy.

Introduction: Alzheimer's disease (AD) remains a major public health challenge, with growing prevalence and limited treatment options that modify disease progression. Recent advances have led to the development and approval of Anti-amyloid-β (Aβ) monoclonal antibodies, which represent a paradigm shift from symptomatic management to targeted disease modification.

Areas ccovered: Agents such as lecanemab and donanemab selectively bind aggregated forms of Aβ and have demonstrated modest but statistically significant slowing of cognitive and functional decline in early AD. However, these therapies are associated with amyloid-related imaging abnormalities (ARIA), particularly in individuals carrying the APOE ε4 allele, necessitating close monitoring and individualized risk assessment. Implementation challenges, including high treatment burden, cost, and real-world applicability, have limited broad clinical adoption. This review examines the mechanistic differences, clinical trial outcomes, and safety considerations of Aβ monoclonal antibodies, while also highlighting emerging therapies and the need for inclusive, precision-guided approaches.

Expert opinion: As research continues to evolve, balancing clinical benefits with safety and accessibility will be critical in defining the role of anti-amyloid-β therapies within the broader landscape of AD care.

Introduction: Canagliflozin (CFZ), is a commonly used sodium-glucose cotransporter-2 inhibitor drug for the management of type 2 diabetes mellitus (T2DM). This review comprehensively compiles existing research studies regarding the clinical pharmacokinetic (PK) behavior of canagliflozin, primarily focusing on exploring effects of different disease conditions, potential drug interactions, and genetic polymorphism.

Areas covered: A comprehensive review of scholarly literature was conducted by using leading databases, i.e. Google Scholar, Science Direct, PubMed, and Cochrane, to identify clinical PK studies of CFZ. The comprehensive literature search identified 25 articles that met the inclusion standards. A linear relationship was observed between the administered doses and PK parameters such as area under the curve from time 0 to infinity (AUC_0-∞) and maximum plasma concentration (C_max). The findings from T2DM patients with moderate renal impairment displayed a 27% increase in AUC_0-∞ of canagliflozin. Furthermore, co-administration of CFZ with rifampin in humans reduced Cmax by 28%, while with telmisartan in rats, CL/F decreased 31.1% initially, but increased 62.9% after 7 days.

Expert opinion: This review integrates all significant human PK parameters of CFZ by combining findings from existing studies, allowing researchers to develop and evaluate PK models for recommending model-based dose optimization.

Protocol registration: CRD420251054714.

Introduction: Drug-resistant tuberculosis (DR-TB) still represents a critical global health threat despite recent therapeutic advances. The shift from long, injectable-based regimens to shorter, all-oral regimens has improved outcomes, yet substantial challenges remain in ensuring efficacy, safety, and equitable access.

Areas covered: We reviewed recent literature (2020-2025) searching PubMed, Medline, Google Scholar, clinicaltrials.gov, WHO guidelines, conference abstract books focusing on recent policy-changing, or knowledge-advancing Phase II/III clinical trials assessing novel DR-TB drugs/regimens.We reported the persisting issues of drug toxicity and acquisition of drug resistance, reviewing evidence from trials, surveillance data, and real-life studies. We provided an overview of new compounds and regimens in the pipeline and underlined the critical role of drug-susceptibility testing.

Expert opinion: The availability of multiple short, all-oral regimens offers unprecedented therapeutic opportunities for drug-resistant tuberculosis. At the same time, the rise in bedaquiline resistance hampers the efficacy of these regimens and represents a global health threat. A promising rich pipeline of new compounds under development holds an important transformational potential in TB treatment; however, integrated drug-diagnostic development is needed to avoid past mistakes. Global advocacy for equitable access to TB treatment is fundamental to pairing scientific progress with concrete impact.

Introduction: Vasovagal syncope is a frequent problem affecting nearly half the population. The symptom burden is wide, ranging from once to hundreds of times. It reduces quality of life and causes injuries. Physicians, particularly front-line physicians such as family doctors, need a simple, practical approach.

Areas covered: We provide context on syncope frequency, competing diagnoses, and natural history, usually characterized by improvement and remissions. Quality of life is reduced and accompanied by anxiety and improves with care. Injuries are common but serious injuries are rare. Treatment begins with advice on salt and fluid intake and physical maneuvers. Fludrocortisone, midodrine, and 2 serotonin-specific reuptake inhibitors are effective, and beta blockers should not be used. Atomoxetine is under investigation. Pacemakers and ablation must be reserved for the rare patient who has not responded to more conservative treatments.

Expert opinion: Patients usually do well and respond to ongoing support and simple dietary advice and physical tips. Some benefit from fludrocortisone, midodrine, or serotonin-specific reuptake inhibitors. Almost all patients eventually stop fainting, and invasive treatments should be used last and for the very few highly afflicted patients who do not improve with safer measures.