Basic & Clinical Pharmacology & Toxicology最新文献

Colorectal cancer is a growing global health concern with complex pharmacotherapy, especially as oral anticancer drugs shift responsibility for adherence to patients. This study explores the experiences of colorectal cancer patients in medication counselling in hospitals and community pharmacies. A qualitative study was conducted through semistructured individual interviews with patients with colorectal cancer (N = 21) from a university hospital. Inductive content analysis was performed using ATLAS.ti software, identifying key categories and subcategories. The following five main themes emerged: sufficiency of counselling; medication reconciliation; management of anticancer medication-related problems; instructions for contacting healthcare; and instructions for medication use. Patients reported varied experiences. Some felt well-informed and confident, while others found counselling insufficient and needed more support. Discrepancies in medication reconciliation were raised, particularly regarding nutritional and herbal products. The pharmacy's role in medication risk management was highlighted, with some patients' medications adjusted based on pharmacy consultation. While side effect management was generally addressed, some patients wanted more detailed information. Challenges in accessing counselling were highlighted, especially during weekends. Medication counselling for colorectal cancer patients should be more consistent across healthcare settings. Strengthening the role of pharmacies and enhancing collaboration and information flow between hospitals and pharmacies is crucial for achieving better patient outcomes.

The accelerating integration of rare earth elements (REEs) in advanced technologies has generated rising concern over human exposure and the attendant toxicological risks. This review presents an up-to-date synthesis of current evidence on REE toxicity across multiple exposure pathways, including inhalation, ingestion and occupational contact, providing an integrative perspective from human clinical data, animal models and in vitro systems. Distinct from traditional reviews, it critically appraises how REE-specific mechanisms, such as oxidative stress, mitochondrial dysfunction and metal ion substitution, produce multiorgan effects with clinical manifestations distinct from those of conventional heavy metals. A key novel finding is the pronounced therapeutic gap. Although chelation is well established for many toxic metals, effective chelation therapy for REE remains largely undeveloped, with current agents like DTPA showing limited efficacy, particularly for gadolinium and cerium, underscoring a major gap in clinical practice. The review highlights vital implications for clinicians, stressing the importance of early exposure recognition, tailored supportive care and the urgent development and validation of REE-specific chelators. Priorities for future research include creating novel chelation strategies and harmonizing international guidance to protect exposed populations. This synthesis aims to equip health professionals, toxicologists and policy-makers with actionable insight, emphasizing the clinical and regulatory urgency of increasing REE exposure and toxicity.

Zhenwu Decoction (ZWD) is a classical formula that has been used for centuries and has the effect of warming yang and promoting diuresis. Clinical research is widely used in urinary, circulatory, nervous, digestive, respiratory and other diseases. ZWD has anti-inflammatory, anti-oxidative stress, anti-fibrosis, immune regulation and other effects. This article elaborates on the components and pharmacokinetics of ZWD, reviews its curative effect and pharmacological action in kidney disease, heart failure, Parkinson's disease and chronic colitis in detail, and summarizes the mechanism of some compounds of ZWD in improving kidney disease. This article provides a reference value for the development and clinical application prospects of ZWD.

Modafinil is approved for excessive daytime sleepiness in narcolepsy, obstructive sleep apnoea (OSA), and shift work sleep disorder (SWSD), but its widespread off-label use raises safety concerns. We evaluated the risk of adverse events (AEs) associated with both labelled and off-label use of modafinil. A systematic search of PubMed, Embase, and Cochrane identified 54 studies that met the inclusion criteria. In labelled uses, narcolepsy patients had significantly elevated risks of diarrhoea (risk ratio [RR]: 2.16, 95% confidence interval [CI]: 1.06–4.41) and nausea compared to those with placebo (RR: 2.44, 95% CI: 1.05–5.72). OSA/hypopnea syndrome patients had higher risks of insomnia (RR: 5.82), anxiety/nervousness (RR: 3.26), and headache (RR: 1.92). SWSD patients had elevated risks of insomnia (RR: 4.09), anxiety/nervousness (RR: 3.85), and nausea (RR: 2.93). Among off-label users, patients with attention deficit hyperactivity disorder had higher risks of insomnia (RR: 4.97) and decreased appetite (RR: 4.21). Patients with major depressive disorder showed higher risks of anxiety/nervousness (RR: 1.95). While modafinil users share common AEs, specific risks vary across patient groups. Our findings on condition-specific AE profiles would support cautious prescribing of modafinil and careful consideration of alternative treatments.

Psychotropic drug concentrations increase/decrease with hydrophilicity/lipophilicity after a low-calorie pre-bariatric surgery diet. To investigate underlying mechanisms, body weight and serum creatinine/cystatin C changes over the diet period were characterized and suggested to reflect changes in glomerular filtration and metabolic capacity, respectively. The greater the individual weight loss, the greater the concentration increase in hydrophilic drugs that undergo glomerular filtration, for example, pregabalin and gabapentin, suggesting that this reflects decreased glomerular hyperfiltration. By contrast, for highly lipophilic drugs, for example, mirtazapine and sertraline, the greater the individual creatinine and cystatin C loss, the greater the decrease in drug concentration, interpreted as increased drug metabolism based on decreased liver inflammation and steatosis. Venlafaxine/O-desmethylvenlafaxine displayed a complicated pattern suggesting the involvement of both glomerular filtration and metabolism. Serum concentrations of modestly lipophilic drugs, for example, duloxetine and (es)citalopram, were not significantly affected by the diet. In conclusion, hydrophilicity- and lipophilicity-related changes in drug concentrations over the diet period covary with markers of changes in hyperfiltration and metabolism, respectively. This implies that weight and creatinine/cystatin C changes could provide quantitative indications regarding expected drug concentration changes following fasting for hydrophilic and lipophilic drugs, respectively, which could be of value when therapeutic drug monitoring is not available.

In lifelong immunosuppressive therapy, missed doses of prolonged-release tacrolimus are almost inevitable and may reduce drug exposure, compromising transplant outcomes. Using pharmacokinetic models, we simulated delayed and missed doses in virtual kidney and liver transplant recipients. Our simulations showed that a missed dose significantly lowers exposure, with recovery taking 2–4 days. For delays shorter than 12 h, the full dose should be taken immediately; for delays between 12 and 24 h, half the dose should be administered; for a missed dose, 150% should be given at the next intake. These strategies may help maintain therapeutic exposure and preserve transplant outcomes.