European Journal Of Clinical Pharmacology[JOURNAL]
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200 papers
A comparison of pharmacometric software programs for atezolizumab population pharmacokinetic simulation.
Zeng Y, Arisa O, Corvalan N … +4 more , Bateman F, Schmidt K, Peer C, Figg WD
Eur J Clin Pharmacol · 2026 Jan · PMID 41553521 · Full text
PURPOSE: We compare our experience with three pharmacometric modeling workflows for simulating alternative dosing regimens of atezolizumab: (1) the gold-standard, NONMEM software used in combination with R, (2) the R-bas...
PURPOSE: We compare our experience with three pharmacometric modeling workflows for simulating alternative dosing regimens of atezolizumab: (1) the gold-standard, NONMEM software used in combination with R, (2) the R-based package RxODE, and (3) the recently developed Julia-based software Pumas, discussing the advantages and limitations of each. METHODS: Our prior work demonstrated that an extended-interval dosing regimen (840 mg q6w) following two standard loading doses maintained efficacy while having a nonsignificant exposure-response relationship with adverse events. In the original analysis, the virtual population was generated in R, simulations performed using NONMEM, and data analysis and visualization then conducted in R. In the present study, we perform the full workflow within R using RxODE for simulation and also recreate this workflow using Pumas in Julia. Pharmacokinetic parameters and graphical output, as well as the processing speed for each method were compared. RESULTS: All three approaches generated comparable virtual populations, key exposure metrics of CMAX, CMIN, and Weekly AUC, and data visualizations of the simulated serum concentrations. However, there were differences in how quickly each software simulated the entire seven cycle dataset, with Pumas simulating 33,273 obs/second, NONMEM 4,782 obs/sec, and RxODE 251 obs/sec. Due to this large difference, the dataset was broken into individual cycles, where NONMEM and RxODE performed comparably at 2041-3337 obs/sec, while Pumas simulated 48,122-69,168 obs/sec. CONCLUSION: All three software produced comparable results. Ultimately, the choice should be based on the modeler’s specific needs and limitations.
Acute coronary syndrome as a turning point for guideline adherence and outcomes in heart failure with coronary artery disease and diabetes mellitus.
Polat F, İnalkaç NKK, Keleş İ
Eur J Clin Pharmacol · 2026 Jan · PMID 41553512 · Publisher ↗
BACKGROUND: Heart failure (HF) patients with concomitant coronary artery disease (CAD) and type 2 diabetes mellitus (DM) represent a particularly high-risk population with increased morbidity and mortality. Acute coronar...
BACKGROUND: Heart failure (HF) patients with concomitant coronary artery disease (CAD) and type 2 diabetes mellitus (DM) represent a particularly high-risk population with increased morbidity and mortality. Acute coronary syndrome (ACS) often serves as a critical event that can trigger optimization of guideline-directed medical therapy (GDMT). However, the impact of ACS on long-term adherence patterns and outcomes in this population remains unclear. METHODS: We retrospectively studied 431 patients with HF (LVEF ≤ 40%), CAD, and DM presenting with ACS between 2019 and 2022. Adherence to nine evidence-based therapies was scored (0-9) and classified as poor (0-3), intermediate (4-6), or good (7-9). Adherence was assessed before ACS and over 36 months of follow-up. Primary outcomes were rehospitalization and all-cause mortality, analyzed using Cox regression and Kaplan-Meier methods. RESULTS: Mean age was 62.1 ± 10.2 years, and 64.7% were male. Before ACS, 45.9% had poor adherence and only 16.0% had good adherence. After ACS, poor adherence dropped to 7.9%, while good adherence rose to 62.2% (p < 0.001). Statin use increased from 22.3% to 82.4%, ACEi/ARB/ARNI from 58.2% to 89.3%, beta-blockers from 44.8% to 86.8%, and MRAs from 23.4% to 67.3%. Gender-specific analyses showed parallel gains: poor adherence declined from 44.8% to 6.5% in men and from 40.1% to 5.3% in women, with good adherence exceeding 67% in both groups. Patients with good adherence had significantly lower risks of rehospitalization (HR 0.52) and mortality (HR 0.46). Independent adverse outcome predictors were low hemoglobin, high HbA1c, impaired renal function, and reduced LVEF. CONCLUSION: ACS serves as a catalyst for improved GDMT adherence in HF patients with CAD and DM. Higher adherence is strongly associated with reduced rehospitalization and mortality, underscoring the need for sustained adherence strategies and multidisciplinary care models to optimize long-term outcomes.
Systematic review and meta-analysis of AI accuracy in warfarin dose prediction across ethnic groups.
Alrabadi B, Marouf M, Bashaireh T … +3 more , Alqudah A, Refai Y, Bandak N
Eur J Clin Pharmacol · 2026 Jan · PMID 41553511 · Publisher ↗
PURPOSE: The primary purpose of this study is to systematically evaluate how accurately artificial intelligence (AI) models can predict optimal warfarin dosing by incorporating both genetic variations-particularly in VKO...
PURPOSE: The primary purpose of this study is to systematically evaluate how accurately artificial intelligence (AI) models can predict optimal warfarin dosing by incorporating both genetic variations-particularly in VKORC1 and CYP2C9-and clinical parameters. METHODS: We searched PubMed, Scopus, and the Cochrane Library from inception until November 2024 for studies using machine learning to estimate warfarin dosing. Mean absolute error (MAE) was the primary outcome. Subgroup analyses were conducted by ethnicity. A random-effects model was used in R Software. RESULTS: Seventeen studies involving 50,859 patients were included. The pooled mean absolute error (MAE) using a random-effects model was 7.10 (95% CI: 5.52, 8.67; p < 0.001). Subgroup analysis by ethnicity revealed varying performance of AI-based warfarin dosing models. For the Asian population (4 studies), the pooled MAE was 4.45 (95% CI: 2.92, 5.97; p = 0.01). In contrast, the White population (3 studies) showed a higher pooled MAE of 10.25 (95% CI: 7.82, 12.68; p < 0.001), and the Black population (4 studies) had the highest pooled MAE at 12.27 (95% CI: 10.95, 13.59; p < 0.001). Funnel plot analysis revealed a symmetrical distribution of studies. For initial dosing algorithms, two studies reported MAEs of 0.24 and 5.43, respectively, reflecting variation based on population size and model type. CONCLUSION: AI-based models enhance warfarin-dosing accuracy, but performance varies by ethnicity. Broader validation, especially in underrepresented groups such as Black populations, and methodological standardization are essential for equitable implementation.
Comparative effectiveness and safety of non-vitamin K antagonist oral anticoagulant-based triple therapy versus dual antiplatelet therapy in patients with atrial fibrillation undergoing percutaneous coronary intervention.
Ku M, Lee YJ, Je NK
Eur J Clin Pharmacol · 2026 Jan · PMID 41553510 · Publisher ↗
PURPOSE: Atrial fibrillation (AF) increases thromboembolic and cardiovascular risks. The optimal antithrombotic strategy for patients with AF receiving percutaneous coronary intervention (PCI) remains controversial owing...
PURPOSE: Atrial fibrillation (AF) increases thromboembolic and cardiovascular risks. The optimal antithrombotic strategy for patients with AF receiving percutaneous coronary intervention (PCI) remains controversial owing to the competing risks of ischemia and bleeding. We hypothesized that non–vitamin K antagonist oral anticoagulant (NOAC)-based triple antithrombotic therapy (TAT) would provide superior ischemic protection than dual antiplatelet therapy (DAPT), without excessively increasing bleeding risk. This study compared the effectiveness and safety of NOAC-based triple antithrombotic therapy (TAT) with DAPT, in AF patients undergoing PCI. METHODS: Using the Health Insurance Review and Assessment database, we conducted a retrospective cohort study on patients with AF who underwent PCI between 2016 and 2021. Patients receiving NOAC-based TAT or DAPT were propensity score matched 1:1. The primary endpoint was a composite of ischemic stroke, myocardial infarction, revascularization, and all-cause mortality. Secondary outcomes included these endpoints individually and major bleeding events. RESULTS: After matching, 3,346 patients per group were enrolled. At 6-month follow-up, TAT was associated with a significantly lower risk of the composite outcome than DAPT (hazard ratio (HR) 0.79, 95% confidence interval (CI) 0.68–0.92; p < 0.01). TAT also reduced the risk of myocardial infarction (HR 0.79, 95% CI 0.62–1.00; p = 0.05), ischemic stroke (HR 0.69, 95% CI 0.48–0.99; p = 0.04), and in-hospital mortality (HR 0.64, 95% CI 0.48–0.87; p < 0.01), with no significant increase in major bleeding (HR 0.91, 95% CI 0.65–1.27; p = 0.59). CONCLUSION: NOAC-based TAT significantly reduced composite cardiovascular events without increasing bleeding risk, supporting its clinical utility in this population.
Oral delivery of an ustekinumab biosimilar with bioavailability comparable to subcutaneous administration in healthy human participants.
Myers JT, Yamaguchi A, Horlen K … +10 more , Fung LC, Vo AT, Mohan D, Hoopes M, Imran M, Van Dam J, Gonen OM, Hashim MA, Dhalla AK, Blauvelt A
Eur J Clin Pharmacol · 2026 Jan · PMID 41553505 · Full text
PURPOSE: Ustekinumab, targeting interleukin (IL)-12 and IL-23, is effective in treating chronic immune-mediated inflammatory diseases, but needs to be dosed via subcutaneous (SC) injection, which impacts patient comfort...
PURPOSE: Ustekinumab, targeting interleukin (IL)-12 and IL-23, is effective in treating chronic immune-mediated inflammatory diseases, but needs to be dosed via subcutaneous (SC) injection, which impacts patient comfort and treatment adherence. To enable oral dosing of ustekinumab, the utility of a robotic pill (RP) was evaluated in humans. METHODS: A Phase 1 study was conducted to evaluate the safety, tolerability, and pharmacokinetics (PK) of single doses (0.5 and 0.75 mg) of an ustekinumab biosimilar (CT-P43) delivered via RP (RT-111) in healthy participants compared to ustekinumab (0.5 mg) administered via SC injection. RESULTS: RT-111 was well-tolerated with no reported SAEs. Ustekinumab was detected in 35/40 participants dosed with RT-111. At the 0.5 mg dose, RT-111 and SC administration yielded similar Cmax (RT-111: 67 ± 7 ng/mL, SC: 56 ± 4 ng/mL), while a dose-proportional increase in Cmax was observed at the 0.75 mg dose (92 ± 8 ng/mL). Uptake via oral delivery was faster, with a Tmax of 3 vs. 10 days for the SC group. Bioavailability of RT-111 was comparable (81%) to that of SC injection. CONCLUSION: This is the first report of successful oral delivery of a therapeutic antibody via an orally ingestible RP in humans, with bioavailability comparable to SC injection. CLINICAL TRIAL NUMBER: Study was registered at Clinicaltrials.gov as NCT05890118 in May 2023.
Beyond fatalities: widening the lens on prescription-opioid harm and digital early-warning systems.
Liu S
Eur J Clin Pharmacol · 2026 Jan · PMID 41553500 · Publisher ↗
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Zanubrutinib in B-cell lymphomas: from clinical pharmacology to therapeutic application.
Chen TB, Yan YT, Sun LN … +2 more , Guo YJ, Wang YQ
Eur J Clin Pharmacol · 2026 Jan · PMID 41553498 · Publisher ↗
PURPOSE: While zanubrutinib, a second-generation Bruton’s tyrosine kinase (BTK) inhibitor, is known for its improved target selectivity, a systematic integration of its clinical pharmacology with efficacy and safety acro...
PURPOSE: While zanubrutinib, a second-generation Bruton’s tyrosine kinase (BTK) inhibitor, is known for its improved target selectivity, a systematic integration of its clinical pharmacology with efficacy and safety across diverse B-cell lymphomas - particularly highlighting its distinct pharmacokinetic and pharmacodynamic profile relative to other BTK inhibitors - is lacking. This review comprehensively summarizes zanubrutinib’s pharmacological characteristics, clinical trial and real-world outcomes, and adverse event management strategies, aiming to provide a clinically actionable resource for optimized and individualized therapy. METHODS: We conducted a structured literature search in PubMed, Embase, Cochrane Library, and Web of Science using keywords including “zanubrutinib,” “BGB-3111,” “BTK inhibitor,” and “B-cell lymphoma.” Relevant publications were critically reviewed to synthesize evidence on zanubrutinib’s pharmacokinetics, pharmacodynamics, clinical efficacy across indications, and management of adverse events, with an emphasis on mechanistic insights and practical clinical guidance. RESULTS: Zanubrutinib demonstrates a favorable efficacy and safety profile supported by its distinct pharmacological characteristics. Its favorable pharmacokinetics include high central nervous system penetration and well-characterized metabolic pathways. Clinically, it induces deep and durable responses across multiple B-cell malignancies, supported by sustained BTK occupancy and a superior free-drug trough concentration relative to its half-inhibitory concentration (IC50). The safety profile is characterized by lower incidences of certain off-target toxicities (e.g., atrial fibrillation) compared to ibrutinib, though infections, bleeding, and cytopenias require vigilant management. Analysis of resistance mechanisms underscores the central role of BTK mutations (e.g., C481S, L528W), informing future therapeutic sequencing. CONCLUSION: This review underscores the value of a pharmacology-guided approach to maximizing zanubrutinib’s benefits, encompassing rational dosing, proactive toxicity management, and strategic positioning within the BTK inhibitor landscape. Future directions should prioritize combinatorial strategies to overcome resistance and therapeutic drug monitoring for precision dosing.
Pharmacokinetic evaluation of doravirine and dolutegravir during paclitaxel-based chemotherapy: a case report in an HIV-positive woman with metastatic pancreatic cancer.
Pozza G, Ridolfo AL, D'Avolio A … +6 more , Matone M, Iannone V, Della Ventura C, Gori A, Cattaneo D, Gervasoni C
Eur J Clin Pharmacol · 2026 Jan · PMID 41553497 · Publisher ↗
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Response to comment on "The role of prescribed opioids in Norwegian overdose deaths in 2005-2021".
Edvardsen HME
Eur J Clin Pharmacol · 2026 Jan · PMID 41553491 · Publisher ↗
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Systematic analysis of the adverse effects of used clinical antisense oligonucleotide drugs in DMD patients based on the FAERS database.
Zhang XF, Hu WG, Hu J
Eur J Clin Pharmacol · 2026 Jan · PMID 41553486 · Publisher ↗
INTRODUCTION: Duchenne muscular dystrophy (DMD) is an X-linked recessive neuromuscular disorder. Building on advancements in oligonucleotide chemistry and delivery, antisense oligonucleotides have emerged as a clinically...
INTRODUCTION: Duchenne muscular dystrophy (DMD) is an X-linked recessive neuromuscular disorder. Building on advancements in oligonucleotide chemistry and delivery, antisense oligonucleotides have emerged as a clinically approved therapeutic modality for treating Duchenne muscular dystrophy. However, the safety assessment of these drugs in clinical application remains limited. METHODS: This study utilized the FDA Adverse Event Reporting System to collect reports of adverse events related to four ASOs: Casimersen, Eteplirsen, Golodirsen, and Viltolarsen. The following four algorithms were used to quantify the adverse event (AE) signals: the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma-Poisson Shrinker (MGPS) models with Empirical Bayesian Geometric Mean (EBGM) estimation. RESULTS: Among 2,760 reports, the predominant AEs included respiratory infections, injection-site reactions, and systemic symptoms. A high reporting odds ratio was observed for poor venous access and product dose omission (Golodirsen, Eteplirsen, Casimersen). Proteinuria was reported for three ASOs (Viltolarsen, Eteplirsen, Casimersen). Among them, Viltolarsen exhibited the most potent signals (ROR = 55.41). Most AEs occurred more than 60 days post-dose (47–53%). CONCLUSIONS: This study confirms the overall safety of four ASO drugs in line with previous publications. The adverse events, such as proteinuria, heart failure, and respiratory failure, highlight the importance of multidisciplinary management. However, limitations inherent to the FAERS database preclude the definitive establishment of causality and the accurate determination of incidence rates.
Influence of pharmacokinetics-related polymorphisms on asciminib exposure in patients with Japanese chronic myeloid leukemia.
Takahashi N, Akamine Y, Miura M
Eur J Clin Pharmacol · 2026 Jan · PMID 41553485 · Publisher ↗
PURPOSE: The effects of polymorphisms in CYP3A4, UGT2B7, ABCB1, ABCG2, ABCC2, NR1I2, and AHR genes on asciminib exposure were evaluated in Japanese patients with chronic myeloid leukemia. METHODS: Plasma concentrations o...
PURPOSE: The effects of polymorphisms in CYP3A4, UGT2B7, ABCB1, ABCG2, ABCC2, NR1I2, and AHR genes on asciminib exposure were evaluated in Japanese patients with chronic myeloid leukemia. METHODS: Plasma concentrations of asciminib (40 mg twice daily [BID] or 80 mg once daily [QD]) were measured by high-performance liquid chromatography. Statistical analysis was performed using SPSS (P < 0.05). RESULTS: For both regimens, the median asciminib area under the concentration-time curve (AUC) was significantly higher in female than in male patients (P = 0.009 and 0.004, respectively). Significant correlations were observed between the asciminib AUC of 40 mg BID or 80 mg QD and body weight (P = 0.042 and < 0.001, respectively). The asciminib AUC of 40 mg BID in patients with the -25385 T allele of the NR1I2 -25385C > T polymorphism was significantly lower than that in patients with the -25385C/C genotype (5363 and 10607 ng∙h/mL, respectively, P = 0.001). In multiple regression analyses, the NR1I2 -25385C > T polymorphism (P = 0.001) and female sex (P = 0.002) were independently predictive of a higher asciminib AUC for the 40 mg BID regimen (determination coefficient: 52.8%), whereas body weight (P < 0.001) and female sex (P = 0.047) were independently predictive of a higher asciminib AUC for the 80 mg QD regimen (determination coefficient: 52.2%). CONCLUSION: Overall, our findings showed that an adjustment of the initial asciminib dose may be needed based on genotyping information for the NR1I2 -25385C > T polymorphism and the body weight of the patient; however, further prospective studies are necessary.
External evaluation of published voriconazole population pharmacokinetic models in adult patients undergoing extracorporeal membrane oxygenation.
Yao Y, Xiang S, Shi H … +6 more , Xiong B, Tan C, Chen Y, Xu Q, Chen X, Meng M
Eur J Clin Pharmacol · 2026 Jan · PMID 41553406 · Publisher ↗
OBJECTIVE: Although numerous population pharmacokinetic (popPK) models of voriconazole have been developed, their predictive performance and extrapolation capacity remain uncertain. This study aimed to systematically eva...
OBJECTIVE: Although numerous population pharmacokinetic (popPK) models of voriconazole have been developed, their predictive performance and extrapolation capacity remain uncertain. This study aimed to systematically evaluate the predictive performance of previously published voriconazole popPK models using an independent external clinical dataset, and to explore potential factors influencing model performance. Additionally, the study sought to identify candidate models with favorable extrapolation capability and clinical utility. METHODS: The external evaluation dataset was derived from critically ill patients receiving extracorporeal membrane oxygenation (ECMO) support. Published voriconazole popPK models were selected and reconstructed. Predictive performance was assessed using both prediction- and simulation-based diagnostic tools. Furthermore, Bayesian forecasting was applied to evaluate the impact of prior information on the model's ability to predict individual plasma concentrations. RESULTS: A total of 76 voriconazole plasma concentrations from 19 patients were included, and 14 published models were included for evaluation. Diagnostic analyses revealed that none of the models fully satisfied the predefined thresholds for clinical acceptability. Both visual predictive checks (VPC) and normalized prediction distribution errors (NPDE) demonstrated varying degrees of predictive bias across all models, with individual models showing adequate performance only in specific diagnostic aspects. Bayesian forecasting indicated that increasing the number of prior concentrations did not consistently enhance predictive performance. In most models, the use of a single prior concentration was sufficient to markedly improve predictive accuracy and precision, achieving optimal performance. Notably, models incorporating allometric scaling exhibited the greatest improvement in Bayesian predictive performance. Whether the time interval between the prior and predicted concentrations affects predictive performance requires further investigation. CONCLUSIONS: Published voriconazole popPK models exhibited considerable variability in predictive performance. Multiple factors, including covariates, patient characteristics, and ethnic variability, may serve as critical determinants of model predictive performance and extrapolation capability. Integrating popPK modeling with maximum a posteriori Bayesian (MAPB) estimation and prior concentration information may serve as an effective approach to achieving model-informed precision dosing (MIPD) for voriconazole. Furthermore, incorporating allometric scaling into models may further enhance the performance of Bayesian prediction.
The impact of anti-gout medications on eight cardiovascular diseases: a Mendelian randomized study.
Peng P, Wang J, Huang M … +6 more , Hu C, Liu S, Liu J, Cai J, Wei X, Sun H
Eur J Clin Pharmacol · 2026 Jan · PMID 41553377 · Publisher ↗
BACKGROUND: Evidence suggests that antigout medications may influence the risk of cardiovascular diseases (CVDs), but findings remain inconsistent and may be biased by confounding and reverse causation due to the observa...
BACKGROUND: Evidence suggests that antigout medications may influence the risk of cardiovascular diseases (CVDs), but findings remain inconsistent and may be biased by confounding and reverse causation due to the observational design of most studies. METHODS: We used a drug‑target Mendelian randomization (MR) approach to investigate the causal effects of genetically proxied inhibition of drug targets for colchicine, non‑steroidal anti‑inflammatory drugs (NSAIDs), and allopurinol on eight CVD outcomes, including angina pectoris, myocardial infarction, coronary artery disease, heart failure, arrhythmia, pericarditis, atrial fibrillation, and ischemic stroke. C‑reactive protein (CRP) was included as a positive control. The inverse variance weighted (IVW) method was used for primary causal estimation, and Bayesian colocalization was performed to strengthen instrument validity. RESULTS: Genetically proxied TUBB6 inhibition (colchicine target) was associated with lower risks of myocardial infarction (OR = 0.951, 95% CI: 0.913–0.990, P = 0.013), coronary artery disease (OR = 0.979, 95% CI: 0.944–0.996, P = 0.025), and heart failure with coexisting obesity (OR = 0.954, 95% CI: 0.917–0.992, P = 0.017). In contrast, genetically proxied PTGS2 inhibition (NSAID target) was associated with increased risks of stable angina (OR = 1.066, 95% CI: 1.010–1.123, P = 0.021), myocardial infarction (OR = 1.079, 95% CI: 1.013–1.148, P = 0.018), and coronary artery disease (OR = 1.045, 95% CI: 1.004–1.088, P = 0.030). Additionally, genetic proxies for allopurinol use showed an association with higher risk of stable angina (OR = 21.371, 95% CI: 2.206–207.026, P = 0.008). Colocalization generally supported shared causal variants. CONCLUSIONS: Our findings suggest that colchicine‑related TUBB6 inhibition may confer cardiovascular protection, whereas NSAID‑related PTGS2 inhibition and allopurinol use may increase CVD risk. These gene‑targeted MR results highlight TUBB6 and PTGS2 as potential biological targets for cardiovascular prevention and risk evaluation.
Determinants of circulating PCSK9 levels and the efficacy of PCSK9 inhibitor therapies in chronic kidney disease: a systematic review.
Ábel T, Benczúr B, Csajbókné ÉC
Eur J Clin Pharmacol · 2026 Jan · PMID 41546841 · Full text
PURPOSE OF REVIEW: Chronic kidney disease (CKD) significantly increases the risk of atherosclerotic cardiovascular disease (ASCVD), with dyslipidemia-particularly elevated low-density lipoprotein cholesterol (LDL-C)-bein...
PURPOSE OF REVIEW: Chronic kidney disease (CKD) significantly increases the risk of atherosclerotic cardiovascular disease (ASCVD), with dyslipidemia-particularly elevated low-density lipoprotein cholesterol (LDL-C)-being a shared risk factor. While statin-based therapies are effective in early-stage CKD, their benefits in dialysis and kidney transplant patients remain inconclusive. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key regulator of lipid metabolism. This review aims to summarize the factors influencing PCSK9 levels in CKD patients and evaluate the safety and efficacy of PCSK9 inhibitors across different stages of CKD. RECENT FINDINGS: Multiple factors have been associated with variations in plasma PCSK9 concentrations in CKD, including glycemic status, proteinuria, renal function, dialysis modality, lipid-lowering therapy, and circadian rhythms. PCSK9 inhibitors, such as alirocumab, evolocumab, and inclisiran, effectively reduce LDL-C and ASCVD risk in patients with mild-to-moderate CKD. However, evidence is limited in patients with advanced CKD (stages 4-5, end stage renal disease (ERSD)), particularly those undergoing dialysis. Elevated PCSK9 levels may not independently predict ASCVD risk in CKD populations. Nonetheless, PCSK9 inhibitors provide a well-tolerated and effective lipid-lowering option in early CKD. Large-scale prospective studies are warranted to clarify their role in patients with ESRD.
Identification of novel signal of DRESS associated with antibiotics: a disproportionality analysis of the FDA adverse event reporting system (FAERS) database.
Goyal K, Sharma R, Datusalia AK … +2 more , Khatik GL, Kumar A
Eur J Clin Pharmacol · 2026 Jan · PMID 41546760 · Publisher ↗
PURPOSE: Antibiotics are widely used in the management of bacterial infections However; most antibiotics are not known for DRESS. Our objective is to find out the association of DRESS with available antibiotics using dis...
PURPOSE: Antibiotics are widely used in the management of bacterial infections However; most antibiotics are not known for DRESS. Our objective is to find out the association of DRESS with available antibiotics using disproportionality analysis. METHODS: Retrospective pharmacovigilance disproportionality analysis based on the FDA Adverse Event Reporting System (FAERS) database from a period of 2004 Q1- 2022 Q3 was conducted using OpenVigil 2.1 tool. Disproportionality measures like Proportional reporting Ratio with associated Chi- square values (PRR ≥ 2 with associated χ2 ≥ 4), ROR with a 95% confidence interval (lower limit of 95% C.I. of ROR is greater than 1), and the number of cases of co-occurrence (n) were used for the identification of novel signals. RESULTS: A total of 13,918 cases of DRESS were reported, out of which 5,455 cases were found with various classes of antibiotics. The signal of DRESS was identified with a total of 40 antibiotics. Sub groups analysis results have shown variation in the strength of signal based on gender, age groups and geographical locations. The sensitivity analysis results have shown a decrease in the strength of signal after removal of cases of concomitant drugs. CONCLUSION: 22 antibiotics were identified which can be associated with DRESS; however, further causality assessment is required to confirm the association.
Effectiveness of treatments for propranolol toxicity: a systematic review of current approaches and evidence.
Hu Y, Mujahid K, Ahsan A … +7 more , Fatima A, Inza, Ahmed MM, Butt MA, Younas S, Aslam MA, Javaid HMA
Eur J Clin Pharmacol · 2026 Jan · PMID 41546730 · Publisher ↗
PURPOSE: Propranolol, a non-selective beta-blocker characterized by high lipid solubility, is extensively prescribed for cardiovascular and central nervous system disorders. Nevertheless, it is frequently implicated in i...
PURPOSE: Propranolol, a non-selective beta-blocker characterized by high lipid solubility, is extensively prescribed for cardiovascular and central nervous system disorders. Nevertheless, it is frequently implicated in intentional overdoses due to its central nervous system penetration and membrane-stabilizing properties, often resulting in life-threatening bradycardia, hypotension, seizures, and cardiac arrest. This systematic review aimed to assess the efficacy of the current medical and mechanical interventions employed in the management of propranolol toxicity. METHODS: A comprehensive literature search was conducted using PubMed, EMBASE, CENTRAL, and Google Scholar for studies published between 1965 and March 18, 2025. Search terms included "propranolol toxicity," "glucagon," "high-dose insulin therapy," "lipid emulsion," "calcium," and "extracorporeal life support." Studies were included if they confirmed propranolol toxicity, evaluated at least one therapeutic intervention, and reported the clinical or hemodynamic outcomes. Expert opinions, narrative reviews, and letters to the editor were excluded from the analysis. RESULTS: A total of 92 studies were included, comprising observational studies, case series, detailed case reports, preclinical animal experiments, and animal control trials. Glucagon emerged as the most frequently utilized pharmacologic agent, followed by high-dose insulin euglycemic therapy (HDIET), intravenous lipid emulsion (ILE), inotropes, and calcium salts. Mechanical interventions such as extracorporeal life support (ECLS), pacing, and hemoperfusion have been reported in severe or refractory cases. The quality of evidence varied, with most studies limited by design heterogeneity, small sample sizes, and a lack of randomized controlled trials. CONCLUSION: Multiple interventions, including glucagon, HDIET, ILE, calcium, and ECLS, have demonstrated benefits in managing propranolol toxicity. However, owing to the low level of evidence and wide variability in patient presentations and treatment protocols, no single therapy exhibits universal efficacy. Individualized multimodal treatment remains essential, and high-quality clinical studies are necessary to establish standardized evidence-based protocols.
Outcomes for metastatic triple-negative breast cancer patients treated with sacituzumab govitecan in clinical studies and real-world studies: a single-arm meta-analysis.
Liang S, Liao W, Jiang J … +2 more , Bao Y, Zheng H
Eur J Clin Pharmacol · 2026 Jan · PMID 41546725 · Publisher ↗
BACKGROUND: Clinical trials have demonstrated favorable outcomes with sacituzumab govitecan (SG) in metastatic triple-negative breast cancer (mTNBC). However, significant differences between trial settings and routine cl...
BACKGROUND: Clinical trials have demonstrated favorable outcomes with sacituzumab govitecan (SG) in metastatic triple-negative breast cancer (mTNBC). However, significant differences between trial settings and routine clinical practice raise concerns about the real-world prognosis of patients with mTNBC. To address this gap, we conducted the first comprehensive single-arm meta-analysis integrating clinical trials and real-world studies (RWSs) to evaluate clinical outcomes and treatment experiences in mTNBC patients receiving SG. METHODS: Relevant studies were searched systematically in seven databases as of November 2024. Clinical trials and RWS of patients receiving SG for mTNBC were included. The primary outcomes of this study were overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and adverse events (AEs). RESULTS: The meta-analysis included 1 randomized controlled trial (RCT), 4 single-arm trials and 9 RWSs with a total of 1387 patients. Direct meta-analysis results showed that the overall random-effects pooled prevalence of OS, PFS, and ORR were 11.26 months (95% CI: 9.68-12.84), 4.88 months (95% CI: 4.34-5.41) and 32% (95% CI: 29%-35%) respectively. Clinical study group demonstrated outcomes of OS: 12.93 months (95% CI: 11.51-14.35), PFS: 5.67 months (95% CI: 5.10-6.25), and ORR: 34% (95% CI: 30%-38%), in contrast to RWS group, with OS: 9.7 months (95% CI: 8.63-10.77), PFS: 4.32 months (95% CI: 3.86-4.79), and ORR: 30% (95% CI: 25%-34%). The most common treatment-related adverse events from SG were neutropenia, nausea, anemia and fatigue. CONCLUSION: This single-arm analysis aims to compile scientific evidence on SG to provide valuable insights into the management of patients with mTNBC. Further randomized trials to analyze its effectiveness and safety are needed. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/ , identifier CRD42024553989.
Levosimendan vs. Milrinone in cardiac surgery: A GRADE-assessed systematic review and meta-analysis.
Emara A, Ellebedy M, Aboeldahab H … +8 more , Nazir A, Elgendy MS, Hassan AM, Barakat Y, Saad OA, Elawady A, Elnady M, Abdelaziz A
Eur J Clin Pharmacol · 2026 Jan · PMID 41546720 · Publisher ↗
BACKGROUND: Levosimendan and Milrinone are commonly used inotropic agents in patients undergoing cardiac surgery; there is a lack of evidence regarding the comparative safety and efficacy of both drugs. We aim to compare...
BACKGROUND: Levosimendan and Milrinone are commonly used inotropic agents in patients undergoing cardiac surgery; there is a lack of evidence regarding the comparative safety and efficacy of both drugs. We aim to compare the clinical efficacy and safety of levosimendan versus Milrinone in these patients. METHODS: We conducted a systematic review and meta-analysis following PRISMA guidelines. PubMed, Scopus, Web of Science, and Cochrane Central were searched up to November 30, 2024, for studies comparing levosimendan and Milrinone in adult and pediatric cardiac surgery patients. We used R statistical software to pool dichotomous data using odds ratio (OR) and continuous data using mean difference (MD) with a 95% confidence interval (CI). RESULTS: Seventeen studies (15 RCTs and 2 observational) involving 890 patients were included. Across all efficacy outcomes, including cardiac index (MD 0.02, 95% CI -0.15-0.19), mean arterial pressure (MAP) (MD -0.09, 95% CI -1.97-1.79), and mPAP (mean pulmonary artery pressure) (MD -0.88, 95% CI -2.66, 0.89), no significant differences were found between the two drugs (P > 0.05). Safety outcomes, including all-cause mortality (OR 0.97, 95% CI 0.48-1.93), acute kidney injury (OR 0.89, 95% CI 0.55-1.44), and arrhythmias (OR 0.87, 95% CI 0.41-1.88), showed no statistically significant differences (P > 0.05). CONCLUSION: Levosimendan and Milrinone showed no significant differences in efficacy or safety in cardiac surgery patients. However, wide confidence intervals indicate potential clinically relevant effects. Current evidence does not favor any single agent universally, supporting individualized use based on patient phenotype and institutional practice. Further high-quality trials are needed to confirm.
Alteplase versus tenecteplase in acute ischemic stroke with large vessel occlusion: a systematic review and meta-analysis.
El Din Moawad MH, Serag I, Abo Elnaga AA … +10 more , Abo-Elnour DE, Abdul-Hafez HA, Hammad MA, Mohamed LA, Mohamed RK, Attia AN, Awad AA, Alkhawaldeh IM, Hegazy M, Abouzid M
Eur J Clin Pharmacol · 2026 Jan · PMID 41546719 · Publisher ↗
BACKGROUND: Intravenous thrombolysis remains a cornerstone in acute ischemic stroke (AIS) management, particularly in large vessel occlusion (LVO). While alteplase has long been the standard thrombolytic agent, tenectepl...
BACKGROUND: Intravenous thrombolysis remains a cornerstone in acute ischemic stroke (AIS) management, particularly in large vessel occlusion (LVO). While alteplase has long been the standard thrombolytic agent, tenecteplase has emerged as a promising alternative due to its pharmacokinetic advantages. This systematic review and meta-analysis aim to compare the efficacy and safety of tenecteplase versus alteplase in AIS patients with LVO. METHODS: A systematic search was conducted across PubMed, Scopus, Web of Science, Cochrane Library, and Embase until February 2025. Studies comparing tenecteplase and alteplase in AIS patients with LVO were included. The primary outcomes were functional independence at 3 months (modified Rankin Scale [mRS] 0-1 and 0-2), mortality, and symptomatic intracranial hemorrhage (sICH). Secondary outcomes included any bleeding, adverse events, and overall complications. Pooled estimates were calculated using risk ratios (RR) and mean differences (MD) with 95% confidence intervals (CI). RESULTS: A total of 14 studies (N = 9641 patients) were included, comprising 5898 patients receiving alteplase and 3743 receiving tenecteplase. No significant differences were observed in 3-month functional outcomes: mRS 0-1 (RR = 0.92, 95% CI: 0.78 to 1.1, P = 0.38) and mRS 0-2 (RR = 0.95, 95% CI: 0.83 to 1.08, P = 0.44). Mortality rates were comparable between groups (OR = 1.07, 95% CI: 0.88-1.30). No significant differences were found in intracranial hemorrhage (ICH) (OR = 1.25, 95% CI: 0.96-1.62), sICH (OR = 1.1, 95% CI: 0.91-1.33), or any bleeding (OR = 1.19, 95% CI: 0.9-1.57). The pooled OR for adverse events was 0.79 (95% CI: 0.53 to 1.17), indicating a comparable safety profile. CONCLUSION: This meta-analysis supports the non-inferiority of tenecteplase compared to alteplase in LVO-associated AIS regarding efficacy and safety. While tenecteplase offers practical advantages, including single-bolus administration and potentially lower costs, further large-scale randomized controlled trials are needed to confirm these findings and optimize thrombolytic selection in stroke care.
Acetylcysteine combined with budesonide nebulized inhalation for the treatment of pneumonia in children: a meta-analysis.
Wei X, Feng L, Chen F
Eur J Clin Pharmacol · 2026 Jan · PMID 41546714 · Publisher ↗
OBJECTIVE: This study aims to evaluate the clinical efficacy and adverse effects of nebulized acetylcysteine combined with budesonide for treating childhood pneumonia, providing a theoretical foundation for its clinical...
OBJECTIVE: This study aims to evaluate the clinical efficacy and adverse effects of nebulized acetylcysteine combined with budesonide for treating childhood pneumonia, providing a theoretical foundation for its clinical application. METHODS: Randomized controlled trials investigating the use of acetylcysteine with budesonide nebulized inhalation for treating pediatric pneumonia were identified through searches in PubMed, EMBASE, Cochrane Library, CNKI, Wanfang Medical Network, VIP, and the Chinese Biomedical Literature Service System. The search period extended from the inception to November 2024. The data analysis was conducted using Review Manager 5.3 and Stata software. For dichotomous outcomes, risk ratios (RR) with 95% confidence intervals (CI) were calculated; for continuous outcomes, standardized mean differences (SMD) with 95% CI were used. Eligible studies were assessed for bias using the Cochrane risk-of-bias tool. Two investigators independently performed literature screening, data extraction, and risk-of-bias assessment. RESULTS: A comprehensive analysis of 30 included studies (enrolling 3,683 pediatric pneumonia patients) demonstrated that nebulized acetylcysteine-budesonide combination therapy significantly improved overall response rate [RR = 1.13, 95% CI: 1.10 to 1.16; P < 0.00001], time to dyspnea resolution [SMD = -1.75, 95% CI: -2.19 to -1.30; P < 0.00001], time to rales resolution [SMD = -2.23, 95% CI: -2.72 to -1.75; P < 0.00001], time to cough resolution [SMD = -2.52, 95% CI: -3.01 to -2.03; P < 0.00001], time to normalization of body temperature [SMD = -2.31, 95% CI: -2.97 to -1.65; P < 0.00001], while reducing adverse events [RR = 0.63, 95% CI: 0.47 to 0.85; P = 0.003]. CONCLUSION: The combination of nebulized inhaled acetylcysteine and budesonide significantly enhances clinical outcomes and lowers adverse effect incidence in pediatric pneumonia treatment. However, as this analysis primarily incorporated studies from China, and given the substantial heterogeneity observed for some outcomes alongside potential publication bias, these findings should be interpreted with caution and warrant further robust validation by future high-quality, multi-center RCTs.
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