British Journal of Clinical Pharmacology

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...

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...

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...

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...

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...

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 ...

The objective of this systematic review and meta-analysis was to identify the interventions used to manage intolerance in patients receiving statins for primary prevention of CVD and to determine the effectiveness of these interventions. This study was conducted according to the PRISMA checklist. The electronic databases MEDLINE (PubMed), SCOPUS, EMBASE, and CINAHL were searched for studies published until June 2025. Based on the NLA definition of statin intolerance, the outcomes were split into...

AO_SCPLOWBSTRACTC_SCPLOWO_ST_ABSINTRODUCTIONC_ST_ABSTreatment response in Alzheimers disease (AD) varies substantially across patients, yet no validated frameworks exist to estimate heterogeneous treatment effects (HTE) from observational data while controlling for confounding bias. METHODSWe developed a causal machine learning framework integrating expert-guided causal graphs, complementary HTE estimators, sensitivity analyses, and policy learning. We applied it to cholinesterase inhibitors (C...

PurposeThe objective of this study was to identify predictors of statin adherence in the primary and secondary prevention of CVD among patients in the first two years after the date of first prescription using real-world data. MethodsThe Electronic Practice Based Research Network Linked Dataset was used in this study. Statin adherence was calculated using a modified proportion of days covered (PDC) formula. Individuals with PDC [≥] 80% during the two years of observation period were consider...

BackgroundPropofol dosing guidelines recommend age-based reductions because hypnotic sensitivity increases in older adults. Most real-world evaluations of induction practice, however, have relied on total weight-normalized dose (mg/kg) rather than estimating cerebral exposure using pharmacokinetic models. Because age-related pharmacokinetic changes alter the relationship between administered dose and peak effect-site concentration (Ce,max), mg/kg surrogates may misrepresent true age-dependent ex...

BackgroundAmiodarone is a widely used antiarrhythmic which frequently induces thyroid dysfunction, including both amiodarone-induced hypothyroidism (AIH) and thyrotoxicosis (AIT). Whether genetic factors contribute to these adverse drug reactions is unknown. In this study, we aimed to identify genetic variants that influence the risk of amiodarone-induced thyroid dysfunction and to evaluate their potential to support genotype-guided risk screening. MethodsThis pharmacogenetic study comprised tw...

ObjectiveThe objective of this study was to explore the predictors of statin intolerance in the primary and secondary prevention of CVD among patients in the first two years after the date of first prescription using real-world data. MethodsThis study used the Electronic Practice Based Research Network Linked Dataset. An algorithm, which considered the muscle symptoms and creatinine kinase of patients, was used to identify statin intolerant patients. The R software was used for all analyses. De...

Amatoxin-induced acute liver failure complicates misidentified foraged mushroom ingestion worldwide; abrupt multisystem collapse punctuates apparent improvement. Our prospective single-arm clinical trial investigated proactive toxicokinetic-based management to preserve elimination capacity: sustained enhanced hydration to maintain renal clearance; fasting plus octreotide to suppress meal-driven enterohepatic circulation; and intravenous silibinin to inhibit OATP1B3-mediated hepatic uptake, enabl...

Maternal smoking during pregnancy is associated with adverse effects on offspring health through impaired placental structure and function. Nicotine and other tobacco-related compounds readily cross the placental barrier, disrupt metabolic pathways, and increase the risk of long-term developmental disorders in newborn. Here, placental metabolic alterations associated with maternal smoking exposure were examined with metabolomics. We used placental samples from the Kuopio Birth Cohort study from ...

BackgroundGLP-1 receptor agonists (GLP-1RAs) and SGLT2 inhibitors (SGLT2Is) have established cardiovascular benefits for patients with type 2 diabetes mellitus (T2DM), with similar class-level effectiveness found in previous studies. However, real-world comparative effectiveness assessments of individual agents remain limited. ObjectivesTo compare the cardiovascular effectiveness of individual GLP-1RAs and SGLT2Is. MethodsWe conducted a multi-national, retrospective, new-user active-comparator...

BackgroundPersonalized pharmacotherapy requires systematic consideration of genetic factors influencing drug efficacy and safety. The accumulation of large-scale whole-exome sequencing (WES) data provides an opportunity to assess population frequencies of clinically significant pharmacogenetic variants; however, the diagnostic applicability of exome data for pharmacogenomics remains insufficiently studied. Materials and MethodsA retrospective analysis of 6,102 anonymized sequencing datasets obt...

BackgroundFatal insulin intoxication remains difficult to diagnose because insulin undergoes rapid degradation after death, limiting the reliability of direct biochemical measurements. This creates diagnostic uncertainty when objective molecular confirmation of insulin excess are required. We hypothesised that insulin excess induces systemic metabolic alterations that persist beyond insulin degradation and can be captured using postmortem metabolomics in a forensic setting. MethodsHigh-resoluti...

BackgroundElevated low-density lipoprotein cholesterol (LDL-C) is a risk factor for cardiovascular disease. Despite available lipid-lowering therapies (LLT), lipid control remains suboptimal. Bempedoic acid offers a non-statin oral treatment for hypercholesterolemia. However, real-world data in Asia are limited. The study aimed to investigate the effectiveness and safety of bempedoic acid in Taiwan. MethodsThis pragmatic phase IV study enrolled 180 patients with inadequately controlled hypercho...

Introduction Vonoprazan, a new oral potassium-competitive acid blocker (PCAB), has shown promise in terms of superior acid suppression when compared to Proton pump inhibitors (PPIs). We evaluated the efficacy of PCABs versus PPIs in preventing rebleeding in high-risk peptic ulcer patients after endoscopic hemostasis. Methods Following the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guidelines, we conducted a comprehensive search for relevant studies across Medline...