RESUMEN
Background: Sunitinib is approved for the treatment of metastatic renal cell carcinoma (mRCC), imatinib-resistant gastrointestinal stromal tumors (GIST), and advanced pancreatic neuroendocrine tumors (PNET). This study aims to investigate the safety profiles of sunitinib through data mining of the US Food and Drug Administration Adverse Event Reporting System (FAERS). Methods: The individual case safety reports (ICSRs) on sunitinib from 2006 Q1 to 2024 Q1 were collected from the ASCII data packages in the Food and Drug Administration Adverse Event Reporting System (FAERS). After standardizing the data, a variety of disproportionality analyses, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the bayesian confidence propagation neural network (BCPNN), and the multi-item gamma Poisson shrinker (MGPS) were employed to identify the potential safety signals of sunitinib-associated AEs. Results: A total of 35,923 ICSRs of sunitinib as the "primary suspected" drug were identified within the reporting period. The search detected 276 disproportionate preferred terms (PTs). The most common AEs, including diarrhea, asthenia, decreased appetite, hypertension, and dysgeusia, were consistent with the drug label and clinical trials. Unexpected significant AEs, such as uveal melanocytic proliferation, salivary gland fistula, yellow skin, eyelash discoloration, scrotal inflammation, were detected. The median onset time of sunitinib-related AEs was 57 days (interquartile range [IQR]16-170 days), with most of the ICSRs developing within the first month (n = 4,582, 39.73%) after sunitinib therapy as initiated. Conclusion: The results of our study were consistent with routine clinical observations, and some unexpected AEs signals were also identified for sunitinib, providing valuable evidence for the safe use of sunitinib in the real-world and contributing to the clinical monitoring and risk identification of sunitinib.
RESUMEN
Two new C-glucofuranosyl flavones apigenin 6-C-ß-glucofuranoside (1) and apigenin 6-C-α-glucofuranoside (2) together with four known compounds (3-6) were isolated from the flowers of Gypsophila oldhamiana. Their structures were elucidated on the basis of extensive spectroscopic analyses. These compounds were evaluated for the cytotoxic activities against four human cancer cell lines and did not exhibit any significant bioactivities (IC50 values > 10 µM).
RESUMEN
Isomers ß-asarone and α-asarone have recently been demonstrated to have differential pharmacological activities. Here, we report an LC-MS/MS method developed using acetonitrile to extract two isomeric phenylpropenes from rat plasma. Separation was achieved using a XDB-C18 column (100 × 2.1 mm; i.d., 1.8 µm) with a mobile phase of methanol-0.1% formic acid (55:45, v/v) at a flow rate of 0.3 mL/min. Calibration curves ranging from 5.20 to 2080 ng/mL for ß-asarone and from 3.68 to 1470 ng/mL for α-asarone were linear (r2 ≥ 0.9938) with the lower limits of quantification being 5.20 and 3.68 ng/mL for both isomers. Intravenous administration of ß-asarone (2.22 mg/kg) and α-asarone (2.36 mg/kg) in rats yielded half-lives of 13.40 ± 4.11 and 28.88 ± 7.82 min with clearance values of 0.196 ± 0.062 mL/min/kg and 0.112 ± 0.012 mL/min/kg for ß-asarone and α-asarone, respectively.