British Journal of Clinical Pharmacology

Hypoglycemia is a common issue in diabetes pharmacotherapy, with seasonal variations potentially influencing its occurrence. It has been reported that blood glucose levels exhibit seasonal variation, suggesting that seasonal factors may influence the occurrence of hypoglycemia. In this study, we examined the seasonal patterns of drug-related hypoglycemia according to causative drug categories using the Japanese Adverse Drug Event Report database. We assessed a total of 545,012 adverse event repo...

Topiramate (TPM) is approved for seizures and migraine prophylaxis and is used off-label for several neuropsychiatric conditions. The available dosage forms, including tablets and sprinkle capsules, are unsuitable for patients who may be unable to take medicine orally. The resulting potential treatment interruptions could have untoward consequences and underscores the importance of developing a parenteral formulation. In this study, we developed a population pharmacokinetic model of a novel, int...

BackgroundDrug suitability is determined by safety, efficacy, and pathological appropriateness. The pharmacogenomics of drug suitability can be assessed by analyzing drug response and drug choice in large population cohorts. MethodsWe investigated drug response and drug choice for dyslipidemia and hypertension using genetic, phenotypic, and prescribing data from the UK Biobank and the All of Us Research Program. Drug response was reassessed with rigorous biomarker scaling, while genome-wide ass...

GLP-1 receptor agonists (GLP-1 RAs) are effective in delaying progression of chronic kidney disease in individuals with type 2 diabetes mellitus (T2DM). We evaluated whether GLP-1 RA prescription is associated with reduced nephrotoxicity in adults receiving long-term lithium therapy. We conducted a retrospective, propensity score-matched cohort study using electronic health records from the TriNetX global network, which includes de-identified data from over 127 million patients across 109 health...

ImportanceGlucagon-like peptide-1 receptor agonists (GLP-1RAs) are fast-growing treatments for type 2 diabetes, obesity, and sleep apnea and are under investigation as potential treatments for many other conditions. The National Institutes of Healths (NIHs) All of Us Research Program offers a robust observational data source for studying questions related to GLP-1RA use in real-world settings. ObjectiveThis article describes key characteristics of All of Us participants who have been prescribed...

Artificial intelligence (AI), particularly large language models (LLMs), is increasingly explored in healthcare, yet its real-world usability and safety in high-risk clinical pharmacy tasks remain uncertain. Vancomycin therapeutic drug monitoring (TDM), which requires precise pharmacokinetic calculations and context-sensitive interpretation within a narrow therapeutic window, provides a stringent test case for AI-assisted decision support. This proof-of-concept study developed and evaluated a hy...

BackgroundGabapentin prescriptions have increased 123% since 2010, reaching 15.5 million Americans annually. Recent studies suggest gabapentin-dementia associations, but whether concomitant medications modify this risk is unknown. Both gabapentin and calcium channel blockers (CCBs) affect neuronal calcium signaling through distinct mechanisms, raising the possibility of pharmacodynamic interaction. MethodsActive comparator new-user cohort study using Rutgers Clinical Research Data Warehouse (20...

ObjectiveDrug poisoning cases due to overdoses of over-the-counter (OTC) medications are increasing, and comprehensive measurement of blood drug concentrations, including OTC drugs, is important in emergency medicine and forensic science. In this study, we developed a simultaneous quantification method for blood drug levels using LC-MS/MS with solid-phase mini-cartridge SmartSPE for sample preparation. MethodsThe target analytes were acetaminophen, caffeine, flunitrazepam, 7-aminoflunitrazepam,...

ContextErogothioniene (EGT), a potent natural antioxidant, exerts hepatoprotection. However, human clinical evidence remains absent. Objectiveto observe the clinical efficacy and safety studies of GeneIII(R) L-Ergothioneine Capsules in the Hepatoprotective Efficacy. Materials and methodsThirty subjects with some abnormal liver function indicators were selected to take 2 capsules of 30mg GeneIII(R) L-Ergothioneine Capsules per day, for 30 consecutive days. The changes in serum liver function bi...

BackgroundBiomedical Large Language Models (LLMs) combined with prompt engineering offer domain-specific reasoning, yet their application to individual-level causality assessment remains unexplored. This study evaluated five combinations of biomedical LLMs, prompting strategies, and causality algorithms by comparing their agreement with two human expert evaluators. Research design and methodsA total of 150 Individual Case Safety Reports (ICSRs) were analyzed: 140 reports from Food and Drug Admi...

BackgroundGlucagon-like peptide-1 (GLP-1) receptor agonists, including liraglutide and semaglutide, are widely prescribed to treat type 2 diabetes mellitus and obesity. Recent anecdotal reports have suggested these agents might be associated with allodynia, a neuropathic pain syndrome, but large-scale epidemiologic evidence is lacking. MethodsTo investigate this potential link, a retrospective cohort study was conducted using the IQVIA PharMetrics(R) Plus database. Adults aged 18 and older who ...

Background Antibiotic pricing is a key determinant of access and stewardship in low- and middle-income countries (LMICs), yet empirical evidence on how prices are formed within pharmaceutical markets remains limited. However, there is little longitudinal evidence on how antibiotic prices behave within national pharmaceutical supply systems. This study evaluated the patterns and determinants of systemic antibiotic pricing in Tanzania using national regulatory import permit data. Methods We conduc...

BackgroundPsychedelics exert widespread effects on brain activity, but their impact on motor function is unclear. This is clinically relevant given the emerging interest in psychedelic-assisted physical therapy for disorders of motor function. This studys primary objectives examined the feasibility and safety of administering movement tasks following low-to-moderate doses of psilocybin in healthy volunteers. MethodsHealthy participants were randomly assigned three psilocybin doses consisting of...

ImportanceAlcohol use is a leading cause of morbidity and mortality worldwide. Growing evidence suggests that glucagon-like peptide-1 receptor agonists (GLP-1RAs) may represent a novel potential pharmacotherapeutic tool for alcohol use disorder (AUD). ObjectiveTo examine the association between GLP-1RA prescriptions and alcohol use. DesignThis cohort study used a cross-sectional measure of alcohol consumption and longitudinal electronic health record (EHR) data collected between 1981 and Octob...

ObjectivesThe 2025 Global Consensus recommends continuing biologics throughout pregnancy in women with inflammatory bowel disease (IBD). Real-world evidence on biologic treatment patterns and outcomes remains limited. This study compared maternal and neonatal outcomes across different biologic use trajectories during pregnancy. MethodsA retrospective study was performed in pregnant women with IBD, treated and/or delivering at the University Hospitals Leuven, Belgium, between 2017 and 2025. Pati...

We designed a platform model that integrates physiologically-based pharmacokinetic (PBPK) modeling with quantitative systems pharmacology (QSP) to bridge translational challenges in antibody-drug conjugate (ADC) development. The PBPK-QSP platform model was developed for the ADC trastuzumab emtansine (T-DM1) in breast cancer patients. This mechanistic framework facilitates translation across preclinical in vitro experiments, in vivo studies, and clinical trials, supporting decision-making for nov...

Reliable pediatric virtual patients are essential for model-informed simulations, including physiologically based pharmacokinetic (PBPK) modeling, to support dose selections in children and to evaluate drug exposure across developmental stages. Despite the availability of extensive pediatric physiological data and age- or size-based models, there remains a lack of well-established, flexible, and scalable approaches for integrating these data into realistic pediatric virtual patients that preserv...

Angioedema is a life-threatening adverse drug reaction associated with renin-angiotensin-aldosterone system (RAAS) inhibitors, characterized by localized swelling in the deep layers of the skin. Well-established evidence indicates an up to fivefold higher incidence of RAAS inhibitor-induced angioedema in self-identified Black patients compared to White patients. The mechanisms underlying this health disparity remain poorly understood and are often attributed to race, a poor proxy for interindivi...

Human genetics has become a cornerstone of drug target discovery, yet the value of Mendelian randomization (MR) for predicting clinical success remains uncertain. Here, we systematically evaluated MR across 11,482 target-indication pairs with documented Phase II clinical outcomes to assess its utility for drug development. We find that MR statistical significance alone does not enrich for Phase II success, in contrast to genome-wide association study (GWAS) support, which confers an increase in ...

BackgroundIn the past two decades, genetic studies have elucidated the contributions of key biological pathways to the pathogenesis of age-related macular degeneration (AMD), including complement activation, lipoprotein metabolism, angiogenesis, and extracellular matrix maintenance. Of these pathways, complement in particular has been observed to dominate the genetic architecture of AMD. Yet, clinical treatment of AMD with complement inhibitors has met with limited success. MethodsUsing data fr...