Pharmaceuticals are widely detected in surface waters, posing significant ecological and human-health risks. China is a major producer and consumer of pharmaceuticals, and widespread contamination has been reported in its surface waters. Regional differences in topography, hydrology, land use, and socioeconomic conditions can shape patterns of pharmaceutical exposure and risk, calling for priority lists tailored to individual river basins. However, previous studies mainly focused on national-scale assessments, selected river basins, or specific pharmaceutical classes. In this study, we systematically reviewed 226 peer-reviewed articles and compiled 8628 occurrence records for 158 pharmaceutical compounds. A multi-criteria prioritization framework that integrated both hazard and exposure potential was used to identify priority pharmaceuticals across nine river basins. Antibiotics were the most frequently detected class of pharmaceuticals, although most had low or moderate priority scores. Erythromycin, roxithromycin, and azithromycin were notable exceptions and ranked highly. Among nonantibiotic pharmaceuticals, estrone and ibuprofen ranked highly in all nine basins. Beyond these shared priorities, several pharmaceuticals showed distinct basin-specific priority pattern. Psychotropic medicines, including diazepam, fluoxetine, sertraline, and citalopram, were identified as priorities in highly urbanized basins, particularly the Haihe and Yangtze River basins. In the Yellow River Basin, the lipid modulator gemfibrozil was prioritized, while in the Pearl River Basin, the veterinary antibiotic salinomycin was prioritized. Combining the rankings with uncertainty estimates showed that high-priority compounds with low uncertainty should be considered for stringent monitoring and control, whereas compounds with high uncertainty require additional occurrence and toxicity data. These findings underscore the importance of basin-scale prioritization in capturing regional differences and provide a basis for tiered monitoring and management in China.

Monogenic familial chylomicronemia syndrome (FCS) is a rare autosomal recessive disorder caused by disrupted intravascular lipoprotein lipase (LPL) pathways. Phenotypic variation often leads to diagnostic delays. We contrast two unique pediatric presentations of FCS, highlighting distinct pathophysiology. Case 1 describes a 21-month-old girl with eruptive xanthomas, which was initially misdiagnosed as an infectious rash, later revealed to be secondary to severe hypertriglyceridemia of 100.6 mmol/L (reference range < 0.8 mmol/L). Molecular testing confirmed a genetic mutation in the GPIHBP1 gene. Case 2 describes a 2-day-old neonate with incidental finding of lipemia during jaundice evaluation, subsequently revealing a fasting triglyceride level of 8.5 mmol/L. Genetic analysis identified compound heterozygous mutations in the LPL gene. Case 1 required intensive insulin therapy, strict dietary fat restriction and adjunctive gemfibrozil. Case 2 was managed via dietary restriction and medium-chain triglyceride formula supplementation. This two-case series illustrates the diagnostic challenges of FCS in pediatric practice and the contribution of molecular confirmation to establishing the underlying aetiology and informing counselling and long-term management.

While pharmacodynamic and pharmacokinetic drug-drug interactions are well established, physicochemical interactions between co-administered oral drug products and their impact on drug absorption remain poorly understood. This study combined biorelevant in vitro testing and physiologically based pharmacokinetic (PBPK) modeling to investigate such interactions between three commercially available drug products SPORANOX (itraconazole), ACTOS (pioglitazone) and GEVILON (gemfibrozil). The in vitro experiments revealed contradictory effects. The apparent solubility of itraconazole was improved in the presence of gemfibrozil, and certain cellulose-based polymers present in ACTOS and GEVILON inhibited precipitation of itraconazole after release from the amorphous solid dispersion. However, in release experiments, Tween 80 present in the GEVILON formulation led to lower itraconazole concentrations due to destabilization of supersaturation. PBPK modeling suggested that this effect could be one of the main reasons for the decreased bioavailability of itraconazole in the presence of the other drug products, as observed in prior clinical studies. This work highlights the potential relevance of physicochemical interactions between different drug products for the efficacy and safety of oral pharmacotherapy. The staged approach presented herein enables early detection of such interactions so that formulation strategies can be applied to mitigate them.

Urban canals frequently convey untreated wastewater to receiving rivers, but in the absence of flow data, tracing this contamination remains a major obstacle for regulatory agencies. To test whether contaminant-mixture structure can serve as a hydrological tracer, we conducted twelve monthly synoptic campaigns across nine stations in the Mae Kha Canal-Ping River system (northern Thailand). Canal stations exhibited a robust, covarying wastewater fingerprint-dominated by ace-sulfame, caffeine, and gemfibrozil-that was entirely absent from the upstream river. This canal signal decayed predictably downstream, yet several wastewater-exclusive compounds remained detectable in the river, confirming persistent urban influence despite substantial in-channel attenuation. Notably, atrazine followed a contrasting river-dominated pattern, demonstrating that external agricultural inputs modify-but do not erase-the canal-derived signature. Our findings introduce a practical, flow-independent framework: by analyzing the covariance of persistent and labile tracers, mixture composition can distinguish urban hydraulic connectivity from simple dilution, even in ungauged catchments. This approach offers regulatory bodies a low-cost diagnostic tool to prioritize canal interceptors and validate river-quality models where conventional monitoring infrastructure is sparse.

Background & aim: Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease that can lead to increased morbidity and mortality. This study described real-world treatment patterns and clinical outcomes by line of treatment among patients with PBC in the US. Materials & methods: Adults (≥18 years) diagnosed with PBC on or after 1 January 17 were identified in the IQVIA PharMetrics[®] Plus database and grouped into newly diagnosed, first-line (1L) and second-line or more (2L+) cohorts. Index date was initial PBC diagnosis or initiation of 1L or 2L therapy; follow-up continued until the earliest of end of continuous enrollment, death or data end. Time to treatment initiation, treatment discontinuation and negative clinical outcomes were assessed with Kaplan-Meier analysis. Results: The newly diagnosed, 1L and 2L+ cohorts included 1748, 1659 and 181 patients, respectively (average age at index: 52.7-54.5 years; female: 84.2-89.0%). Of the newly diagnosed cohort, 34.8% did not initiate PBC treatment within 1.5 years post-diagnosis. In the 1L cohort, median time from diagnosis to 1L initiation was 1.2 months; median time from 1L initiation to 1L discontinuation/2L initiation was nearly 5 years. In the 2L+ cohort, median time from 2L initiation to 2L discontinuation was approximately 4 years. In the untreated, 1L, and 2L+ cohorts, 18.9%, 14.4% and 19.3% of patients developed ≥1 negative clinical outcome post-index (usually cirrhosis). Conclusion: Results of this US population-based study demonstrate a potential unmet need for early intervention and effective treatment options for patients with PBC, as one in three patients with PBC remain untreated years after diagnosis.

Constructed wetlands are widely recognized as nature-based solutions for improving water quality in systems receiving treated wastewater. However, their effectiveness depends primarily on hydrological connectivity, contaminant properties, and hydraulic residence time. In Mediterranean wetlands, where strong hydrological variability and seasonal water scarcity influence water quality dynamics, understanding attenuation processes under contrasting water-circulation scenarios is relevant for protecting sensitive downstream ecosystems. This study assessed the capacity of a semi-natural pond system i.e., a series of interconnected shallow ponds comprising both natural and managed water bodies that receive treated wastewater while retaining natural wetland characteristics, located upstream of the Fuente de Piedra Ramsar wetland main basin (southern Spain) to reduce nutrients and emerging contaminants under contrasting water-circulation scenarios. Across 26 sampling events, substantial reductions were observed when treated wastewater flowed through the semi-natural pond system before reaching the main wetland basin, including decreases of 75% in total nitrogen. Marked attenuation was detected for emerging contaminants with shorter environmental half-lives, such as trimethoprim, naproxen, caffeine and selected triazine metabolites showed removals exceeding 70-90%, whereas more persistent substances, including carbamazepine and gemfibrozil, exhibited limited reduction. In contrast, negligible changes occurred during a temporary bypass configuration put in place for restoration works, in which treated wastewater avoided most of the semi-natural ponds before reaching the main wetland basin. Dry-season conditions enhanced contaminant attenuation, largely reflecting lower flows and extended hydraulic residence times. Cumulative ecotoxicological risk, estimated using risk quotients (RQsample) based on measured environmental concentrations and the lowest predicted no-effect concentrations for freshwater organisms, declined downstream under the regular flow pathway, particularly for pesticides, but moderate risk persisted under the bypass scenario. Overall, the semi-natural pond system demonstrates a strong but hydrologically dependent capacity to mitigate nutrient and emerging contaminant loads entering a Mediterranean Ramsar wetland. Nevertheless, elevated phosphorus concentrations and the persistence of certain emerging contaminants highlight the limitations of natural attenuation alone and support the integration of complementary management and treatment strategies to ensure long-term ecosystem protection.

We report a silver(I)-catalyzed three-component A3-coupling strategy for the synthesis of 2-chloro-(phenylvinyl)imidazo[1,2-a]pyridines from 2-aminopyridines, terminal alkynes, and β-chlorovinyl aldehydes. The transformation proceeds under mild conditions with high regioselectivity, broad substrate scope, and excellent functional-group tolerance. Notably, retention of the vinylic C-Cl bond in the products provides access to structurally important chlorovinyl-substituted imidazo[1,2-a]pyridines. The retained chlorovinyl motif may offer potential value for further diversification and for the development of medicinal chemistry-oriented scaffolds and pharmacophores. The protocol is operationally simple and scalable, as demonstrated by gram-scale synthesis. Its synthetic utility is further highlighted through the late-stage functionalization of complex molecules, including Naproxen and Gemfibrozil, as well as the synthesis of amino acid-derived 2-chloro-(phenylvinyl)imidazo[1,2-a]pyridines. These results underscore the versatility of the protocol and its potential applications in medicinal chemistry, molecular diversification, and drug discovery.

Glioblastoma (GBM) is a highly aggressive and therapy-resistant brain tumor. In our earlier study, we demonstrated that the antihyperlipidemic drug Gemfibrozil, when repurposed, exerts strong cytotoxic effects on GBM cells by modulating autophagy. In the present study, we further investigated the complex interplay among key homeostatic pathways, specifically autophagy, endoplasmic reticulum (ER) stress, and calcium signalling, following Gemfibrozil exposure in the context of GBM progression and treatment resistance. Our findings reveal that Gemfibrozil-induced inhibition of autophagy triggers the unfolded protein response (UPR), leading to activation of ER stress pathways, as evidenced by altered expression of canonical markers, including IRE1α, PERK, and CHOP. Notably, CHOP silencing reduced levels of cleaved Caspase-3 and Caspase-9, confirming the involvement of ER stress-mediated apoptosis following disruption of autophagy. Moreover, the induction of ER stress and inhibition of autophagy were accompanied by disturbances in calcium homeostasis, demonstrated by reduced expression of the calcium-binding proteins Calmodulin and Calreticulin. This imbalance resulted in mitochondrial calcium overload, loss of mitochondrial membrane potential, and elevated reactive oxygen species (ROS) production, ultimately culminating in caspase activation and cell death. Mechanistically, PGC-1α emerged as a key regulator of Gemfibrozil-mediated anti-tumor activity. Collectively, our findings uncover a critical molecular cascade involving suppression of autophagy, induction of ER stress, calcium dysregulation, mitochondrial dysfunction, and oxidative stress that drives GBM cell death. These insights not only highlight Gemfibrozil as a potential therapeutic agent but also emphasize the importance of targeting homeostatic vulnerabilities in GBM.

No relevant published information exists on the use of gemfibrozil during breastfeeding. Because of a concern with disruption of infant lipid metabolism, gemfibrozil is best avoided during breastfeeding. An alternate drug is preferred, especially while nursing a newborn or preterm infant.

This study investigated genetic determinants of the pharmacokinetics of the CYP2C8 index drugs repaglinide and gemfibrozil, and their interaction in healthy participants. Sequencing data from a study with montelukast revealed a novel functional CYP2C8 allele (rs2071426, CYP2C8*19), predicted to create an intronic splice donor site. In human liver samples, CYP2C8*19 associated with transcript-specific changes in CYP2C8 mRNA expression, reduced CYP2C8 protein expression, and decreased enzyme activity. Consistently, participants with the CYP2C8*19/*19 genotype had 45% greater area under the plasma repaglinide concentration-time curve from time zero to infinity (AUC0-∞) than participants with CYP2C8*1/*1 (P = 1.6 × 10[-4]). Participants with CYP2C8*1/*3 had 26% smaller AUC0-∞ (P = 0.0033) and those with CYP2C8*1/*4 had 51% greater AUC0-∞ (P = 8.2 × 10[-4]). The fold increase in repaglinide AUC0-∞ caused by gemfibrozil was 36% (P = 1.3 × 10[-4]) smaller in CYP2C8*19/*19 participants than in CYP2C8*1/*1 participants. In a genome-wide association study (GWAS), SLCO1B1 c.521 T>C (rs4149056) associated with increased repaglinide AUC0-∞ (P = 4.5 × 10[-15]; n = 172) and SLCO1A2 variants associated with decreased AUC0-∞ (P < 10[-8]). In a GWAS of repaglinide after gemfibrozil pretreatment, SLCO1C1 variants associated with decreased AUC0-∞ (P < 1.6 × 10[-8]; n = 66). Participants with the poor function SLCO1B1 genotype showed a 32% smaller fold increase in repaglinide AUC0-∞ following gemfibrozil than participants with the normal function SLCO1B1 genotype (P = 0.0045). This study characterizes CYP2C8*19 as a novel decreased function allele and shows that CYP2C8 and SLCO1B1 genotypes affect the gemfibrozil-repaglinide interaction.

This study introduces a twin enrichment strategy based on dual-template molecularly imprinted polymer-assisted solid-phase microextraction coupled with dispersive liquid-liquid microextraction (MISPE-DLLME) for the simultaneous extraction and determination of favipiravir and remdesivir in biological matrices (blood and urine), followed by high-performance liquid chromatography with ultraviolet detection (HPLC-UV) analysis. The dual-template molecularly imprinted polymer (DT-MIP) was synthesized via precipitation polymerization and comprehensively characterized using Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), field-emission scanning electron microscopy (FESEM), Brunauer-Emmett-Teller (BET) surface area analysis, simultaneous thermal analysis (STA), and X-ray diffraction (XRD). Under optimized conditions, including pH 2.00 ± 0.1, 10.0 mg of MIP, 200 ± 5 μL of 1-dodecanol, 500 ± 10 μL of methanol, and an extraction time of 10.0 ± 0.5 min, the method afforded high recoveries of 103-110% with relative standard deviations (RSDs) below 5% (n = 3). The method showed excellent sensitivity, with limits of detection of 1.0 ng/mL for favipiravir and 0.40 ng/mL for remdesivir and limits of quantification of 3.3 ng/mL and 1.3 ng/mL, respectively. Selectivity was evaluated against ten structurally related drugs (ibuprofen, gemfibrozil, paracetamol, diazepam, clobazam, methocarbamol, theophylline, naproxen, dimenhydrinate, and cinnarizine) at various concentration ratios, and the DT-MIP displayed superior recognition performance compared with the corresponding non-imprinted polymer (NIP). Analysis of clinical samples yielded acceptable recoveries and precision, confirming the reliability of the proposed method and its potential applicability in therapeutic drug monitoring of COVID-19 antivirals.

Herein, we have established a palladium-catalyzed domino protocol for the synthesis of polycyclic frameworks under microwave irradiation. The transformation proceeds via a three-fold cascade, enabling the efficient construction of two C-C bonds and one C-N bond in one pot with various functional groups. The method's applicability was demonstrated through drug diversification derived from cholesterol, ibuprofen, and gemfibrozil, as well as scale-up reactions. Furthermore, the photophysical properties of these motifs were investigated.

Pharmaceuticals and personal care products (PPCPs) as well as current-use pesticides (CUPs) are considered to be contaminants of emerging concern (CECs), but there is limited information that exists about their occurrence and impact in the marine environment. A database of these CECs has been created as an overview of their occurrence and distribution in European marine waters by the ICES Marine Chemistry Working Group (MCWG) and collaborators from various European countries. The majority of the compiled data corresponded to pharmaceuticals in seawaters, but much less data were available for other matrices (biota and sediment) and CEC groups. Generally, concentrations were characterized for a limited spatial area and/or a small number of species/organisms. A Total Occurrence Index (TOI) was developed, taking into account the number of data available, the maximum concentrations and the frequency of detection together as indicators. The TOI provided estimates for the CECs in the database and has been used to identify the most relevant PPCPs and CUPs. The highest TOIs were found for the pharmaceuticals salicylic acid, hydrochlorothiazide, gemfibrozil, mefenamic acid, paracetamol and diclofenac; the PCPs 2-ethylhexyl-4-methoxycinnamate, 4-methylbenzylidene camphor, octocrylene, galaxolide, benzophenone-3 and tonalide; and the CUPs chlorpyrifos, chlorthal-dimethyl, simazine and irgarol. It is noted that additional data are required, particularly in the sediment and the biota matrices, to more fully understand the distribution and impact of these CECs in the marine environment, when considering the wide geographical distribution areas covered in this review. Further assessment is also required, to prioritise those CECs, based on which of them are expected to cause the most adverse toxic effects to marine ecosystems.

The occurrence, spatiotemporal distribution of 22 pharmaceutically active compounds (PhACs) was comprehensively investigated in the Pearl River Basin. Caffeine, cimetidine, and acetaminophen were the most ubiquitous compounds in the studied region. The total concentrations of all detected PhACs ranged from 9.89 to 42.07 ng∙L-1 during the wet season, and from 18.33 to 202.85 ng∙L-1 during the dry season. Hierarchical clustering indicated that the compositional associations among PhACs differed between the wet and dry seasons, while the principal coordinate analysis further demonstrated a distinct differentiation between seasonal periods. This study explores the application of USEtox in the Pearl River Basin as a complementary approach for evaluating and prioritizing PhACs. Characterization factors of PhACs were calculated using the USEtox model, with ecotoxicity characterization factors ranging from 101 to 104 CTUe∙kg-1 and human toxicity characterization factors ranging from 0 to 10-4 CTUh∙kg-1. Caffeine, gemfibrozil and 2-(4-Chloro-2-methylphenoxy) propanoic acid are the compounds with the highest potential toxicity impact scores. Notably, some PhACs (fenofibrate and paroxetine) exhibited comparatively low environmental concentrations but achieved relatively high potential ecotoxicity impact scores. This study explored a multidimensional risk assessment approach for PhACs in subtropical river basins, providing scientific basis for identifying priority control substances.