Expert Review of Clinical Pharmacology最新文献

Introduction: Orally administered valganciclovir (VGCV) is rapidly metabolized to ganciclovir (GCV) and is used to prevent and treat cytomegalovirus (CMV) infection. Although GCV exposure is related to efficacy or toxicity, therapeutic drug monitoring (TDM) for GCV has not yet been clinically implemented. This review was conducted to summarize relevant current issues for implementing the optimization of VGCV therapy based on TDM.

Areas covered: The current knowledge on the population pharmacokinetics of GCV after oral administration of VGCV, the relationships between GCV exposure with efficacy and toxicity, and the available evidence for TDM was comprehensively reviewed. The limited sampling strategy (LSS) and microsampling methods for clinically implementing TDM are summarized. The relationship between nucleoside-diphosphate-linked moiety X-type motif 15 (NUDT15) polymorphisms and toxicity is discussed. Relevant literature published before 2025 was searched in PubMed.

Expert opinion: Accumulating evidence indicates that GCV exposure is associated with both efficacy and safety, and exposure-guided dosing (target area under the time-concentration curve (AUC) of 40-60 μg·h/mL) may provide a reliable approach for maximizing VGCV therapy. However, several methodological and practical challenges, including standardization of LSS and improvement of microsampling technologies, are required for practical VGCV dose optimization in all patient populations.

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: 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: 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: 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 h.

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 seven 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 h. 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.

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.