Expert Review of Clinical Pharmacology最新文献

Introduction: Proton pump inhibitors (PPIs) are widely used to treat acid-related disorders; however, treatment response varies significantly due to Cytochrome P450 2C19 (CYP2C19) genetic polymorphisms that alter individual drug metabolism. Such variation can lead to insufficient acid suppression, resulting in treatment failure or adverse events. Genotype-guided PPI therapy represents an important step toward personalized gastroenterology by optimizing drug efficacy and safety.

Areas covered: This review summarizes evidence from clinical trials and meta-analyses examining CYP2C19-mediated differences in the pharmacokinetics and pharmacodynamics of PPIs in both adults and children. Relevant literature was identified primarily through PubMed and clinical guidelines, covering publications from 1989 to 2025. The review focuses on outcomes related to gastroesophageal reflux disease (GERD), Helicobacter pylori eradication, and eosinophilic esophagitis. Current trials indicate that genotype-guided, tailored PPI therapy - through dose adjustment, drug selection, or regimen modification - can improve treatment efficacy and control abdominal symptoms without increasing safety risks or costs.

Expert opinion: CYP2C19 genotype-guided therapy constitutes a practical approach to personalized medicine for acid-related disorders. Barriers to widespread implementation include limited test availability, uncertain cost-effectiveness, and insufficient clinician awareness. Future directions include integrating multi-gene pharmacogenomic testing, model-informed dosing, and artificial intelligence-based decision support to advance individualized acid suppression and personalized gastroenterology.

Introduction: Vitiligo is a chronic autoimmune skin disorder characterized by progressive melanocyte loss, resulting in well-demarcated depigmented patches that significantly impact quality of life. Affecting 0.5-2% of the global population, vitiligo poses both psychosocial and therapeutic challenges. Despite multiple conventional therapies such as corticosteroids, calcineurin inhibitors, and phototherapy, durable repigmentation remains difficult to achieve.

Areas covered: This review summarizes recent advances in understanding the emerging medical treatment of vitiligo. A targeted literature search was conducted using PubMed, Embase, and ClinicalTrials.gov from inception to April 2025. Key clinical trial data are discussed to evaluate efficacy, safety and durability of response across therapeutic classes.

Expert opinion: The approval of topical ruxolitinib marks a pivotal step toward precision therapy in vitiligo. Ongoing studies of combination and maintenance regimens offer promise for sustained repigmentation and disease stabilization. However, optimizing long-term outcomes requires continued translational research to elucidate mechanisms of relapse, improve accessibility of emerging therapies and personalize treatment strategies to individual disease phenotypes.

Introduction: 27.1 million adults in the United States have alcohol use disorder (AUD). However, current medications for AUD have mixed efficacy. As such, a shift in treatment approach and the development of novel pharmacotherapies for AUD is imperative.

Areas covered: This review addresses novel insights on treating AUD through precision medicine that identifies subgroups of individuals most responsive to existing single or combination pharmacotherapies for AUD. In parallel, this review synthesizes the emergence of pharmacological agents for AUD that are on the treatment horizon. These include glucagon-like peptide 1 receptor agonists, classic psychedelics, ketamine, immune modulators, and cannabinoids. Data reviewed were culled from searches of the PubMed database and clinicaltrials.gov registry.

Expert opinion: Adopting a precision medicine approach and investigating novel compounds for AUD treatment requires a shift in systems of care. Precision medicine navigates away from the traditional 'one size fits all' health care model to emphasize the individual, leading to long-term cost-effectiveness and improved patient outcomes. Moreover, novel pharmacotherapies face challenges in the scale of their distribution throughout healthcare settings. The developments reviewed in this paper elucidate a paradigm shift necessary to facilitate the integration of precision medicine and the adoption of novel pharmacotherapies within the AUD field.

Introduction: Depression remains a leading cause of disability worldwide. Conventional treatments, such as pharmacotherapy and psychotherapy, are first-line interventions but are limited by partial efficacy, tolerability issues, and delayed onset of action. In this context, non-implantable neuromodulation techniques can be an important tool in clinical practice addressing some of these limitations, and are the scope of this review.

Areas covered: This review synthesizes evidence on non-implantable neuromodulation for major depressive disorder, covering established modalities (ECT, MST, rTMS, tDCS, tACS) and emerging approaches (FUS, PBM, tTIS, PNS and tPEMF). Mechanisms, efficacy, tolerability, and accessibility are discussed. PubMed/MEDLINE was searched from inception to 1 November 2025, prioritizing systematic reviews, randomized trials, major guidelines, and large observational studies, with reference-list screening.

Expert opinion: Non-implantable neuromodulation therapies are evolving from experimental interventions to validated clinical options. Rather than competing with pharmacotherapy, they should be viewed as complementary components within a multimodal framework. The future of depression management likely depends on the integration of pharmacological and neuromodulatory approaches to optimize response, tolerability, and functional recovery.

Background: Piperacillin population pharmacokinetic models reportedly perform poorly for critically ill females compared to males. We aimed to explore potential methods that may better adjust for female data during model development.

Research design and methods: Total piperacillin concentrations were used from a prospective observational study in NONMEM v7.5.1. Two models were developed following different approaches: classic stepwise approach and sex-specific approach. Relationship between covariates and estimated parameters were explored by statistically and graphically assessing their performance on males and females separately. Dosing regimen simulations were also performed separately by sex.

Results: A one-compartment model based on data from 70 critically ill patients (49/21 males/females) with 233 concentrations best fit the data with both approaches. Creatinine clearance was the most significant covariate for the classic approach model, while creatinine clearance was best for male patients and estimated glomerular filtration rate was best for female patients with the sex-specific approach. Dosing recommendations were different between male and female patients with the sex-specific model.

Conclusion: This study is the first to consider sex-specific covariates during the modeling process for piperacillin in critically ill patients. This approach may help reduce differences in model predictions between males and females in model-informed precision dosing strategies.

Objective: This study aimed to identify risk factors associated with mitral annular calcification (MAC) in patients with hypertrophic obstructive cardiomyopathy (HOCM) and to evaluate its relationship with clinical outcomes.

Methods: A total of 310 patients with HOCM who underwent interventricular septal myectomy were retrospectively analyzed. Patients were divided into a MAC group (n = 24) and a non-MAC group (n = 286). Demographic characteristics, echocardiographic parameters, and clinical data were compared between groups. Major adverse cardiovascular and cerebrovascular event (MACCE) and circulating levels of brain natriuretic peptide, Apelin, and Galectin-3 were analyzed.

Results: Patients with MAC were older and showed higher prevalence of aortic annular calcification, mitral leaflet thickening, and moderate-to-severe tricuspid regurgitation (P < 0.05). Multivariate analysis identified gender, age, aortic annular calcification, moderate-to-severe tricuspid regurgitation, and mitral leaflet thickening as independent risk factors for MAC. Patients with MAC showed larger left ventricular end-diastolic volume, reduced left ventricular ejection fraction, and greater left atrium mass, and a higher incidence of MACCE than those without MAC (P < 0.05).

Conclusion: In HOCM undergoing septal myectomy, MAC is associated with adverse cardiac remodeling and unfavorable clinical outcomes. Identification of related factors may aid risk stratification and perioperative management.

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.