Polypharmacy is a major concern in pediatric intensive care units (PICUs), where critically ill children receive multiple medications, increasing the risk of clinically significant potential drug–drug interactions (pDDIs). However, data on pDDI prevalence in PICUs remain limited. This study investigates the prevalence, characteristics, and risk factors of pDDIs in PICU patients.
A nationwide, cross-sectional point prevalence study was conducted in 50 Turkish PICUs, including hospitalized patients (1 month–18 years) receiving ≥ 2 medications. Demographic, comorbidity, medication use, mortality scores, ventilation status, and infection data were collected. pDDIs were identified by Lexicomp interactions and classified as A (no interaction), B (mild), C (moderate), D (severe), and X (contraindicated), with only D and X interactions analyzed.
Among 517 patients (median age: 18.0 months [IQR: 7.0–60.0], 59.8% male), 51.2% (95% confidence interval [CI]: 46.8–55.6) had a clinically significant pDDI (D or X category). The most common X category interactions were chloral hydrate–furosemide (1.8%) and fluconazole–domperidone (1.2%), while D category interactions included fentanyl–midazolam (13.6%) and fentanyl–levetiracetam (6.0%). Risk factors for pDDIs included higher PRISM score (OR = 1.0; 95% CI: 1.0–1.0; and p < 0.001), increased number of medications (OR = 1.5; 95% CI: 1.4–1.6; and p < 0.001), polypharmacy (OR = 13.6; 95% CI: 6.1–30.3; and p < 0.001), mechanical ventilation (OR = 3.7; 95% CI: 2.5–5.6; and p < 0.001), and presence of infection (OR = 22.2; 95% CI:1.5–3.2; and p < 0.001).
This study confirms a high prevalence of clinically significant pDDIs in Turkish PICUs, mainly due to polypharmacy, organ dysfunction, and comorbidities. The high prevalence of fentanyl–midazolam interactions highlights the need to differentiate between harmful interactions and therapeutic synergies. Integrating clinical pharmacists and developing pediatric-specific pDDI software are crucial to enhancing medication safety.
Rheumatoid arthritis (RA) is a chronic autoimmune disease marked by persistent synovitis, cartilage damage, progressive disability, and a significant decline in quality of life. The advent of biologics and small molecule inhibitors has substantially improved disease management and reduced disability. However, the long-term impact of these therapies on disease progression and functional outcomes remains a critical area of ongoing research.
This analysis aims to evaluate the efficacy, safety, and disability outcomes of various therapeutics for RA by analyzing completed Phase 4 interventional clinical trials registered on ClinicalTrials.gov.
A systematic analysis of ClinicalTrials.gov was conducted on October 28, 2024, focusing on completed Phase 4 interventional studies with results, targeting RA treatments. Inclusion criteria covered studies involving biologics, small molecule inhibitors, and combination therapies aimed at managing RA. Key outcome measures such as Disease Activity Score 28 (DAS28), The American College of Rheumatology response criteria, patient-reported outcomes, and disability-related measures were extracted and analyzed.
The analysis found that therapeutic advances, including TNF inhibitors, IL-6R inhibitors, and JAK inhibitors, demonstrated significant efficacy in reducing disease activity and improving functional outcomes. Long-term data revealed that these treatments delay or reduce disability progression, although differences in safety profiles were noted, particularly with JAK inhibitors showing an increased risk of thromboembolic events.
Phase 4 clinical trials provide real-world evidence of the effectiveness and safety of RA therapeutics, with a positive impact on disability management. Ongoing research and postmarketing surveillance are essential to optimizing treatment strategies and addressing residual disability in RA patients.
Ginkgo biloba extract (EGB), a traditional Chinese medicine extracted from the Ginkgophyta, was used to regulate various neurological disorders (NDs). Limited compatibility data exist on EGB after marketing with other drugs administered simultaneously through the Y-site. This study aimed to determine the compatibility of EGB during simulated Y-site administration with 35 continuous infusion drugs that are commonly administered in the neurological intensive care units (NICUs).
The compatibility of EGB with these drugs was determined using a well-established experimental model to simulate Y-site administration. EGB (0.35 mg/mL) was mixed in a volume ratio of 1:1 with the secondary drug solution to simulate Y-site coadministration procedures in NICUs. All other drugs were prepared at maximum concentrations commonly administered in the clinical setting. Compatibility was assessed by visual inspection (observations of haziness, color change, or precipitate formation), the Tyndall effect, chromaticity, pH, turbidity, insoluble particles, and UV absorption at 0, 1, 2, and 4 h postmixing.
This study has identified 25 (71%) combinations that are compatible and 10 combinations that are incompatible within four hours. Visual changes occurred with EGB + acyclovir and EGB + ganciclovir. The turbidity of the mixed solution of EGB + calcium gluconate exceeds the specification. Binary combinations of EGB + aceglutamide, EGB + aescin sodium, EGB + amiodarone hydrochloride, EGB + fosfomycin, EGB + ganciclovir, EGB + meropenem, EGB + omeprazole, and EGB + vinpocetine had particles that grew over the limitation of the Chinese Pharmacopoeia specification. Both admixtures of EGB + acyclovir and EGB + amiodarone hydrochloride absorption at 420 nm and 550 nm exceeded the prescribed limits.
It is strongly advised against combining EGB 0.35 mg/mL with acyclovir, aceglutamide, aescin sodium, amiodarone hydrochloride, calcium gluconate, fosfomycin sodium, ganciclovir, meropenem, or omeprazole, as well as vinpocetine. If coadministration is inevitable, a larger volume of saline (NS) or dextrose 5% in water (D5W) should be used to flush the port catheter before and after the EGB infusion to clean the lumen of the port catheter.
The present study was conducted to establish a population pharmacokinetic (PK) model that describes tigecycline concentrations in critically ill patients and optimises the detailed dosing regimens of tigecycline via Monte Carlo simulations.
A single-centre, prospective, observational study was conducted on 155 patients hospitalised in the intensive care unit (ICU) with 458 plasma samples. This work enrolled 115 eligible patients (348 plasma samples) to establish the population PK model with various covariates and the other 40 patients (110 plasma samples) were validated on such a model. Monte Carlo simulations were performed to calculate the probability of target attainment (PTA) of proposal dosage regimens.
The two-compartment model of zero-order absorption and first-order elimination can be used to fully describe the concentration–time curve of tigecycline. The estimated values of population PK parameters were 16.3 and 40.7 L/h for clearance (CL) and Q, respectively, and 145 and 345 L for the volumes of the central and peripheral compartments. Creatinine clearance (CrCL) was the only factor that exhibited a relation to systemic CL in the final PK model, with a CrCL adjustment factor of 0.00692. According to dose simulations, the standard dosage regimen only sufficed for pneumonia patients with a low value of minimal inhibitory concentration (MIC = 0.25 mg/L) or renal dysfunction (MIC ≤ 1 mg/L, estimated glomerular filtration rate (eGFR) ≤ 60 mL/min/1.73 m2). High doses of tigecycline were needed in such patients with a high MIC or a normal/high renal CL rate. For complicated intra-abdominal infections, the standard dose can achieve a high PTA when MIC ≤ 0.5 mg/L and under nonaugmented renal CL conditions. For complicated skin-structure infections, the standard dose can only achieve the expected therapeutic effect for patients with MIC = 0.25 mg/L and renal dysfunction (eGFR ≤ 60 mL/min/1.73 m2).
The recommended standard dosage regimen of tigecycline is insufficient for most critically ill patients. This study provides detailed dose regimens of tigecycline for ICU patients based on infection type and renal function.
K. M. A. Zinnah, A. N. Munna, J.-W. Seol, and S.-Y. Park, “Impaired Autophagic Flux by Citalopram Inhibits DR5 Degradation and Increases TRAIL-Mediated Apoptosis,” Journal of Clinical Pharmacy and Therapeutics, vol. 2025 (2025). https://doi.org/10.1155/jcpt/7538839.
In the article titled “Impaired Autophagic Flux by Citalopram Inhibits DR5 Degradation and Increases TRAIL-Mediated Apoptosis,” there was an error in Figure 1(j) related to an incorrect image being used to represent the morphology of the Calu-3 cells.
This error was introduced by the authors during figure assembly and should be corrected as follows:
We apologize for this error.
Drug repurposing offers a time- and cost-effective means for drug development. Accordingly, the accurate prediction of human efficacy is crucial for its success. Organoids have emerged as valuable tools for evaluating compound efficacy in three-dimensional environments closely resembling in vivo organs. However, a comprehensive overview of their application in drug repurposing is lacking. This systematic literature review discusses the origins, applications, and target diseases of organoids employed for drug repurposing.
A systematic search of original articles published up to March 5, 2025, was conducted in PubMed using the keywords “organoid” and “drug repurposing.” Trends in publications, organoid sources, research objectives, and target diseases were analyzed.
Research on drug repurposing using organoids initially emerged in 2016 and has grown rapidly since the 2020s. Patient-derived tissue organoids, primarily derived from cancer tissues, are the most used. Organoids derived from pluripotent stem cells are mainly utilized for organs that are difficult to obtain from human tissues. These organoids are most frequently used for evaluation of the efficacy of repurposed drug candidates identified through other methods as well as for the primary screening of existing drug libraries, demonstrating broad utility for drug repurposing research. Most target diseases are cancers, with colorectal cancer being predominant. Organoids are anticipated to play increasingly important roles in drug repurposing, particularly for organs with limited tissue availability and complex three-dimensional structures, as well as for a diverse range of diseases beyond cancer.
This study is the first to comprehensively review the use of organoids for drug repurposing. These findings provide valuable insights for researchers pursuing drug repurposing and encourage effective integration of organoids into drug repurposing strategies.
A large amount of knowledge has accumulated regarding the pharmacology of most cancer types, including their side effects, and during the last decade, many novel agents have emerged, accompanied by increased costs for healthcare systems.
Artificial intelligence (AI) was applied in healthcare services, and the benefit of its use in the prediction of the targets of low molecular weight compounds that can affect biological processes was assessed (proportion of the top predicted targets, common name, target class and probability).
Designing the chemical agent or molecule chosen and the program will give the protein target prediction immediately by AI. A tuning algorithm device, with new information input in the web application interface, was used.
Information was arranged in order and fed to an in silico target prediction/Swiss TargetPrediction (STP). This tool is a computational method used to predict the most probable protein targets of small molecules, as well as to envisage what happens when many chemotherapy drugs are combined in cancer treatment. It aids in understanding some molecular processes controlling specific physical traits or biological activities to elucidate probable beneficial and adverse consequences. In addition, it helps to predict imprecision of defined molecules and pave the way to drug repositioning. Prediction is carried out employing the ligand-based drug design (LBDD), which enables comparison of the correlation between the molecule under examination and the known binding molecules of a large set of target proteins.
Target activity profiles enable a systematic repurposing process by extending the target profile of drugs, and then drug repurposing with AI provides a cost-effective strategy to reuse approved drugs for new medical indications and the availability of new treatments, reduces development costs and mitigates risks due to the cost of the cancer drug agents, coupled with high cancer disease prevalence, which means the current cost trajectory is untenable for most world healthcare systems.
Chimeric antigen receptor T-cell therapy (CAR-T) is an emerging therapy for malignancies, including refractory B-cell lymphoma, follicular lymphoma, multiple myeloma, and chronic lymphocytic leukemia. Postmarketing monitoring is essential to ensure the rational administration of CAR-T because of its high occurrence rate of adverse events. Thus, we collected the adverse event reports from the FAERS database between the first quarter of 2017 and the second quarter of 2025. Disproportion analysis methods, including the reporting odds ratio and information component, were used to identify potential hematological AEs associated with CAR-T therapy. A total of 47,118,226 reports were analyzed, and 99,497 adverse events associated with CAR-T-cell therapy were identified. We found 11,689 hematological adverse events accounted for 11.75% of the total adverse events, of which cytopenia (ROR025 = 33.87, IC025 = 4.95), hemophagocytic lymphohistiocytosis (HLH, ROR025 = 28.20, IC025 = 4.71), and myelodysplastic syndrome (MS, ROR025 = 34.41, IC025 = 4.98) were highly underrated in the real world. All six CAR-T products were associated with hematological adverse events, and the typical hematological adverse events varied among different products. A high proportion and frequency of death outcomes were identified after CAR-T-related hematological adverse events, such as thrombocytopenia, HLH, and cytopenia. Cytokine release syndrome frequently overlapped with hematological adverse events, including cytopenia, HLH, and thrombocytopenia. Our results may help clinicians identify rare but potentially fatal hematological AEs at an early stage, effectively reducing the risk of lethal hematological toxicity of CAR-T therapy.
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