Purpose: Imatinib is the first-line treatment for patients with gastrointestinal stromal tumors (GIST) after surgery. However, its pharmacokinetic profile varies remarkably between individuals and has not been well characterized in postoperative Chinese patients with GIST. Therefore, this study aimed to develop a population pharmacokinetic (PPK) model and recommend appropriate doses for different patients to achieve the target trough concentration in such a population. Patients and Methods: A total of 110 surgically treated GIST patients were enrolled, of which 85 were applied to conduct a PPK analysis with a nonlinear mixed-effect model and 25 for external validation of the model. Demographic and biomedical covariates, as well as six single nucleotide polymorphisms were tested to explore the sources of variation in pharmacokinetic parameters of imatinib. Monte Carlo simulations were performed to establish the initial dosing regimens. Results: A one-compartment model was established in postoperative GIST patients. The red blood cell count (RBC) and ABCG2 rs2231142 were observed to have a significant effect on the clearance of imatinib. The typical values estimated by the final model were 9.72 L/h for clearance (CL/F) and 229 L for volume of distribution (V/F). Different from the fixed dose regimen of 400 mg each day, patients carrying rs2231142 heterozygous type and with a lower level of RBC (2.9 × 10¹²/L), 300 mg imatinib daily is enough to achieve the target trough concentration. When RBC rises to 4.9 × 10¹²/L, 500 mg daily is recommended. For patients with rs2231142 GG genotype, 500 mg a day is required at RBCs of 3.9 × 10¹²/L and 4.9 × 10¹²/L. Conclusion: RBC and rs2231142 contribute to the pharmacokinetic variation of imatinib and personalized dose recommendations based on patient characteristics may be necessary.

Objective Osimertinib plays a crucial role in patients with non-small cell lung cancer (NSCLC). However, the haematological toxicities caused by osimertinib in such a population have not been well characterised. This analysis was performed to determine the incidence of osimertinib-related haematological toxicity in patients with NSCLC. Method A literature search was conducted in PubMed, Embase, Cochrane Library and Web of Science. Eligible studies were included to describe the pooled incidences of anaemia, neutropenia and thrombocytopenia secondary to osimertinib in NSCLC patients. Results 1288 patients from 10 studies were enrolled in this study. The overall incidences of osimertinib-related all-grade anaemia, neutropenia and thrombocytopenia in NSCLC patients were 21.1% (95% CI 10.9% to 33.3%), 14.6% (95% CI 5.9% to 26.1%) and 28.4% (95% CI 12.4% to 47.6%), respectively. In items of high-grade haematological toxicities, there were 0.5% (95% CI 0.1% to 1.1%) for anaemia, 2.0% (95% CI 0.3% to 4.6%) for neutropenia and 0.4% (95% CI 0% to 1.1%) for thrombocytopenia. Conclusions There is non-negligible haematological toxicity associated with osimertinib, and it should be taken seriously.

Xanthii fructus (XF), a traditional Chinese medicine, is commonly used for anti-inflammatory and analgesic purposes; however, its hepatotoxicity limits its use to some extent and the underlying mechanisms remain unclear. The present study aimed to explore the key targets and molecular pathways of XF-induced liver injury through an integrated network toxicology and molecular docking approach. Potential hepatotoxic components of XF were screened using the TCMSP and comparative toxicogenomics database databases. Targets associated with these components and liver injury were identified via SwissTargetPrediction, GeneCards, and online Mendelian inheritance in man. Protein–protein interaction networks were constructed using STRING and analyzed with Cytoscape. The Metascape platform was used for gene ontology/Kyoto encyclopedia of genes and genomes enrichment analysis, and molecular docking was performed to validate the interactions between the key components and targets. Five hepatotoxic active ingredients were finally screened, involving 74 hepatotoxic targets, and significantly enriched pathways were uncovered through rigorous Kyoto encyclopedia of genes and genomes analysis. The most prominent was pathways in cancer [ P <.001; false discovery rate (q-value) <0.001], followed by Hepatitis B [ P <.001; false discovery rate (q-value) <0.001]. Among them, TP53, HSP90AA1, JUN, and EP300 served as core targets. Molecular docking confirmed the strong binding affinity between the key targets and hepatotoxic components (binding energy: −6.83 to −9.28 kcal/mol). This study provides a preliminary framework for XF-induced hepatotoxicity, highlighting multi-component, multi-target interactions. Mechanistic predictions require preclinical validation. Future work should validate these findings experimentally and explore detoxification strategies to enable safer clinical use of XF.

Aim: To assess the role of genetic polymorphisms in postoperative imatinib concentrations and edema in patients with gastrointestinal stromal tumor. Methods: The relationships between genetic polym...

Objective Improper use of human albumin (HA) is now common in clinical settings. This study aims to explore the feasibility of the plan-do-check-act (PDCA) cycle in promoting the rational use of HA. Methods The differences between the control and observation groups (after the PDCA cycle) in terms of serum albumin detection rate, serum albumin values, HA usage, and rationality were analysed and compared using a before-and-after control method. Results A total of 372 patients were recruited, including 186 in each of the control and observation groups. On comparison, it was observed that the overall use of HA improved after the PDCA cycle compared with the preintervention period, and the rational rate of HA prescriptions increased from 68.3% to 96.2%. The serum albumin detection rate before applying for HA increased from 83.9% to 98.9%, and the median values decreased from 26.7 (22.8–30.9) g/L to 24.7 (22.7–27.2) g/L. Regarding the use of HA, the median amount of HA used was reduced by 20 g compared with the preintervention period, meanwhile, the median duration was shortened by 2 days. Conclusion The PDCA cycle is desirable when employed to promote the rational use of HA.