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Almonertinib was included in the first‐line treatment of non‐small cell lung cancer with EGFR T790M mutations by the Chinese Society of Clinical Oncology in 2021. Considering that immunocompromised lung cancer patients are prone to opportunistic fungal infections, and most triazole antifungal drugs are moderate or strong inhibitors of CYP3A4, this study was conducted to develop and validate an accurate and rapid ultra‐performance liquid chromatography tandem mass spectrometry method for quantifying almonertinib in plasma and for investigating the pharmacokinetic changes of almonertinib caused by voriconazole and fluconazole in rats. After liquid–liquid extraction with tert‐butyl methyl ether, an XSelect HSS T3 column (2.1 × 100 mm, 2.5 μm, Waters) was used for the chromatographic separation of almonertinib and sorafenib‐D3 (internal standard). The analytes were detected using an AB Sciex Triple Quad 5,500 mass spectrometer in the positive ionization mode. The method exhibited great linearity (0.5–200 ng/ml, r > 0.997) and stability under the established experimental conditions. All validation experiments were in accordance with the guidelines, and the results were all within the acceptable limits. This method was successfully applied to the researches of pharmacokinetics and drug interactions for almonertinib in rats. Voriconazole and fluconazole significantly altered the pharmacokinetic profiles of almonertinib and increased the systemic exposure of almonertinib in rats to different degrees, but further human trials should be conducted to validate the results. [ABSTRACT FROM AUTHOR]

Objective; To introduce the hazard vulnerability assessment (HVA) method to the risk management of high-alert drugs, and also to analyze the hospital's ability to withstand high-alert drug risk factors, so as to clarify the priorities and make useful explorations for the hospital's control of high-alert drugs. Methods : The HVA method was used to identify and evaluate the potential risk events for high-alert drugs in the hospital, and then the risk assessment items were assessed and ranked in order, so as to identify high risk events demanding top priority management. Results : There were 13 risk items in the management and control of high-alert drugs in the hospital, of which 2 items were of moderate risk level, i. e. the prescription dosage error and neglect of error prescriptions in prescription review, and other items were of all low risk level. Conclusion : The HVA method could be applied to the management of high-alert drugs in the hospital. Specific contermeasures to strengthen risk management in accordance with risk factors could not only reduce the risk of safe drug use caused by hazard vulnerability of high-alert drugs, but also provide assistance for safe and effective management of high-alert drugs. [ABSTRACT FROM AUTHOR]

Although farrerol, a characteristically bioactive constituent of Rhododendron dauricum L., exhibits extensive biological and pharmacological activities (e.g., anti-oxidant, anti-immunogenic, and anti-angiogenic) as well as a high drug development potential, its metabolism remains underexplored. Herein, we employed ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry coupled with multiple data post-processing techniques to rapidly identify farrerol metabolites produced in vivo (in rat blood, bile, urine and feces) and in vitro (in rat liver microsomes). As a result, 42 in vivo metabolites and 15 in vitro metabolites were detected, and farrerol shown to mainly undergo oxidation, reduction, (de)methylation, glucose conjugation, glucuronide conjugation, sulfate conjugation, N-acetylation and N-acetylcysteine conjugation. Thus, this work elaborates the metabolic pathways of farrerol and reveals the potential pharmacodynamics forms of farrerol. [ABSTRACT FROM AUTHOR]

Background: Lenvatinib (LEN) is approved as first-line therapy for advanced hepatocellular carcinoma (HCC). Schisantherin A (STA) can exert hepatoprotective and anti-tumor effects. The clinical combination of LEN and STA is very common, especially for patients with advanced HCC, but the effect of STA on the pharmacokinetics of LEN is unclear. This study aimed to investigate the effects of STA on the pharmacokinetics of LEN in rats and explore its potential mechanism., Methods: Male Sprague-Dawley (SD) rats were orally administered different doses of STA or vehicle control for 7 consecutive days, and 1.2 mg/kg of LEN was given on day 7. The messenger RNA (mRNA) and protein expression levels in the intestines and liver were investigated by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot., Results: It was revealed that STA increased the oral bioavailability of LEN. The area under the curve from time 0 to infinity (AUC 0-∞ ) and maximum plasma concentration (C max ) of LEN after co-administration with STA (20 mg/kg) increased by 54.3% (3,396.73±989.35 vs. 5,240.03±815.49 µg/L/h) and 54.8% (490.64±124.20 vs. 759.66±152.75 µg/L), respectively. The clearance decreased from 0.38±0.12 to 0.23±0.04 L/h/kg, and the apparent volume of distribution (Vz) decreased from 10.83±3.19 to 6.35±1.38 L/kg in the presence of 20 mg/kg STA. In addition, the expression of P-glycoprotein (P-gp) mRNA and protein in the intestines was markedly decreased., Conclusions: This study showed that STA increased the bioavailability of LEN, probably due to inhibition of P-gp in the intestine, thereby increasing systemic absorption of LEN. Thus, there is an interaction between the two drugs, and careful monitoring must be conducted when they are used in combination., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-22-174/coif). The authors have no conflicts of interest to declare., (2022 Journal of Gastrointestinal Oncology. All rights reserved.)

A 74-year-old female patient was admitted to hospital following a road accident with pains in the chest, abdomen, waist, back, nose, left wrist and lower limbs. After 1 week, the patient presented with gastrointestinal bleeding, and thus was treated with protein pump inhibitors (PPIs), including lansoprazole, esomeprazole and omeprazole enteric-coated tablets, in order to inhibit acid secretion and attenuate bleeding. However, the patient developed skin rashes on the chest and right lower limb and foot 28 days following treatment initiation. The skin rashes spread and ulcerated after 3 days, and were associated with tracheal mucosal injury and hemoptysis. Subsequently, treatment of the patient with PPIs was terminated, after which the tracheal hemoptysis and skin rashes markedly improved. In addition, no new skin rashes appeared following termination of the PPI treatment. In the present case, long-term treatment of an elderly patient with PPIs may have induced exfoliative dermatitis, due to hepatic ischemia, hypoxia and acute renal failure, which may have decreased the metabolism of PPIs, resulting in the accumulation of PPI metabolites.