Expert Review of Clinical Pharmacology最新文献

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: Metamizole, a non-steroidal anti-inflammatory drug and moderate inducer of cytochrome P450 enzymes (CYP3A4, CYP2B6, CYP2C19), has gained increased use in clinical practice. This retrospective study evaluates the number of drug-drug interactions (DDIs) associated with metamizole when prescribed for ≥24 hours.

Research design and methods: Data were collected from the electronic healthcare records of adult patients prescribed metamizole at Tergooi Medical Center between June 2017 and May 2024. Relevant DDIs with metamizole were identified using the Metamizole DDI Manager developed by Global DDI Solutions. Only clinically relevant, i.e. orange (action may be needed) and red (contra-indicated), DDIs that occurred during or within 7 after discontinuation of metamizole treatment in a hospital setting were considered.

Results: A total of 37,110 unique patients received at least one metamizole prescription of which 2.6% (n = 968) were treated for ≥24 hours. Of these, 98.6% (n = 954) were prescribed at least one interacting medication. In total, 3680 DDIs were identified, corresponding to an average of 3.8 DDIs per metamizole prescription. Of the 98 interacting medications identified, 95% were classified as orange, and 5% as red.

Conclusions: In conclusion, metamizole is associated with a many DDIs in clinical practice. This highlights the need for careful monitoring when prescribed.

Introduction: Little is known about the pharmacokinetics (PK) and pharmacodynamics (PD) of Δ⁹-tetrahydrocannabinol (Δ⁹-THC) when vaped in liquid formulations. As prevalence of vaping Δ⁹-THC in liquid forms grows, understanding the factors that influence PK/PD profiles is critical to guide future research and cannabis regulation.

Areas covered: Currently, no human studies have elucidated the PK/PD profile of Δ⁹-THC from vaped liquids, as confirmed by searches of PubMed and Embase. Using existing research on smoked cannabis and nicotine-containing e-cigarettes, this review examines the potential influence of product potency, vaporization efficiency, consumer use behaviors, aerosol bioavailability, and other constituents on the PK/PD profile of Δ⁹-THC vaped in liquid forms. Further, we hypothesize whether the PK/PD of Δ⁹-THC in liquid forms may differ from smoked cannabis and address potential regulatory implications (United States-focused) of novel vaping products.

Expert opinion: While more potent than smoked cannabis, vaped liquid formulations with Δ⁹-THC may have a similar PK/PD profile through modulation of Δ⁹-THC delivery by consumer use behaviors. Potential health effects of high-potency vaping products with Δ⁹-THC in liquid form need to be carefully studied. Lastly, researchers should continue to think creatively about how this important work can progress while restrictions on Δ⁹-THC continue to hinder research.

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.

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.