Immune thrombocytopenia (ITP) is an uncommon yet clinically significant cause of thrombocytopenia in multiple myeloma (MM). We report a case of an 80-year-old female with severe thrombocytopenia identified during routine follow-up after breast cancer surgery, leading to the simultaneous diagnosis of Smoldering multiple myeloma (sMM) and secondary ITP. Laboratory findings, including an elevated immature platelet fraction, increased platelet-associated immunoglobulin G (IgG), and preserved megakaryopoiesis, supported a diagnosis of immune-mediated platelet destruction. The patient demonstrated only a transient response to corticosteroids but achieved sustained remission with eltrombopag (EPAG), while maintaining stable M-protein levels and showing no myeloma-defining events (MDEs). This report highlights the importance of considering secondary ITP in the evaluation of patients with MM.

This study presents the development and application of a Gastrointestinal Performance Simulation System (GTPS) as a predictive in vitro tool for assessing the bioequivalence potential of Eltrombopag olamine formulations. Due to the poor aqueous solubility and complex ionization behavior of Eltrombopag, conventional dissolution methods often fail to predict in vivo performance accurately. The GTPS integrates multiple compartments with biorelevant media, peristaltic pumping, orbital agitation, and continuous sampling to mimic physiological gastrointestinal transit. Candidate generic formulations containing 75 mg of Eltrombopag olamine were evaluated alongside the innovator product (Revolade®) to identify formulations with optimal in vivo performance potential. The GTPS demonstrated improved predictive correlation with bioequivalence results compared to conventional dissolution testing. Test batches that appeared similar during dissolution analysis showed distinct release profiles when assessed with the GTPS. The GTPS provides a robust, biorelevant alternative to conventional dissolution tests, supporting the selection and optimization of formulations for bioequivalence studies of BCS Class II compounds such as Eltrombopag.

Cancer remains a global health challenge, driving the search for more effective therapeutic agents due to the limitations of existing treatments. We evaluated the anticancer potential of Eltrombopag olamine on MCF-7 (breast adenocarcinoma) and SMMC-7721 (hepatocellular carcinoma) cell lines. Eltrombopag olamine demonstrated dose-dependent antiproliferative effects, with IC50 values of 31, 154, and 127 µg/ml for MCF-7, SMMC-7721, and non-cancer HEK293T cell lines, respectively. Apoptosis induction in MCF-7 and SMMC-7721 cell lines was confirmed through Hoechst 33342 staining-assisted detection of condensed nuclei. FITC-annexin V/PI staining showed a significant increase in late apoptosis in both MCF-7 and SMMC-7721 cells, as well as necrosis in SMMC-7721 cells. The cell cycle analysis revealed S-phase arrest in both MCF-7 and SMMC-7721 cell lines and a remarkable increase of sub-G1 phase in SMMC-7721 cells. Caspase-dependent apoptosis was evidenced by reduced cell death in the presence of Caspase-3/7, -8, and - 9 inhibitors. In MCF-7 cells, FAS, TP53, BAX, TNFα, and cytochrome-C were upregulated, while ERK expression was downregulated. In SMMC-7721 cells, TP53, BAX, and TNFα were similarly upregulated, whereas ERK, STAT3, MAPK, NOTCH, PARP1, and EGFR expression levels were reduced. The results show the involvement of mitochondrial (intrinsic), EGFR-MAPK-ERK, WNT1, and death receptor signaling pathways in the apoptosis process. Interactions of Eltrombopag with EGFR, FAS, p53, and TNFα proteins were detected through molecular docking simulations. These findings highlight the potential of Eltrombopag olamine as a repurposed, multi-targeted therapeutic candidate for the treatment of breast and liver cancer.

The recent pandemic has highlighted the impact of diseases on global health and the economy. The rapid discovery of new hit molecules remains a tough challenge. Pharmaceutical impurity profiling can be linked to drug discovery through the identification of new hits from compounds identified during the analytical profiling. The present study demonstrates this linkage through the extension of the impurity (forced degradation) profiling of eltrombopag (ELT) olamine, a thrombopoietin (TPO) receptor agonist. The drug was exposed to standard degradation and the degradation products were primarily resolved and identified by UPLC-ESI-MS. This led to the identification of five forced degradation products (FDP). Thirty-three other known related substances (RS) of ELT, identified in the literature, were also considered. Molecular similarity checks were performed using Tanimoto/Jaccard's similarity searches. A set of structurally and topologically similar molecules, including ELT and 15 RS, was established and subjected to in-silico toxicity-, absorption-, distribution-, metabolism-, and elimination (ADME) predictions. The RS, predicted with similar or lower toxicity than ELT and a comparable ADME profile, were subjected to molecular docking to trace changes in TPO receptor affinity. The results indicated that five RS had a high Jaccard's similarity with ELT and higher or comparable docking scores. These compounds, along with few other impurities were predicted to have lower toxicity, better or comparable absorption, distribution, metabolism, and also a better excretion profile than ELT. This justifies their entry as potential novel TPO receptor agonists in drug discovery.

Eltrombopag, a nonpeptide thrombopoietin receptor agonist, is primarily used for treating immune thrombocytopenic purpura. The aim of this study was to investigate the pharmacokinetic profile and food-drug interaction of test and reference eltrombopag olamine tablets among healthy Chinese volunteers. An open, randomized, single-dose, 2-period crossover design was employed, involving fasting and fed conditions with a 10-day washout period. Ninety-six healthy volunteers received a single oral dose of 25 mg of the 2 eltrombopag formulations, with 48 participants in each group: fasting volunteers and those consuming a high-fat, low-calcium meal. Plasma eltrombopag concentrations were analyzed using liquid chromatography-tandem mass spectrometry, and pharmacokinetic parameters were derived from the concentration-time profiles. The geometric mean ratios, with 90% confidence intervals, for the maximum plasma concentration, area under the concentration-time curve from time 0 to the last measurable concentration, and area under the concentration-time curve from time 0 to infinity fell within the bioequivalence acceptance criteria (80%-125%) under both fasting and fed conditions, indicating bioequivalence between the test and reference formulations. Administration of eltrombopag with a high-fat, low-calcium diet reduced the net systemic exposure by approximately 40%. Adverse events were recorded, and no serious adverse events were observed in either fasting or fed conditions. In conclusion, eltrombopag is well tolerated and exhibits a favorable safety profile in the Chinese population. The achievement of bioequivalence under fasting and fed conditions supports the demonstration of biosimilarity between the test and reference formulations.

Herein, we developed a rapid, one-step, and cost-effective methodology based on the fabrication of water-soluble self-nitrogen, sulfur, and phosphorus co-doped black seed carbon quantum dots (BSQDs) via microwaveirradiation in six minutes. Our synthesis approach is superior to those in the literature as they involved long-time heating (12 h) with sulfuric acid and sodium hydroxide and/or high temperatures (200 °C). A full factorial design was applied to obtain the most efficient synthesis conditions.BSQDs displayed excitation-independent emissions, demonstrating the purity of the synthesized BSQDs, with a maximum fluorescence at 425 nm after excitation at 310 nm. Eltrombopag olamine is an anti-thrombocytopenia drug that is also reported to cause toxicity in river water based on its Persistence, Bioaccumulation, and Toxicity (PBT). The synthesized BSQDs were employed as the first fluorometric sensor for environmental and bioanalysis of eltrombopag. The fluorescence of BSQDs decreased with increasing concentrations of eltrombopag, with excellent selectivity and sensitivity down to 30 ppb. BSQDs were successfully applied as sensing probes for the detection of eltrombopag in medical tablets, spiked and real human plasma samples, and river water samples, with an overall recovery of at least 97 %. The good tolerance to high levels of foreign components and co-administered drugs indicates good selectivity and versatility of the proposed methodology. Plasma pharmacokinetic parameters such as t1/2, Cmax, and t max of eltrombopag were evaluated to be 9.91 h, 16.0 μg mL[-1], and 5 h, respectively. Moreover, the green character of the BSQDs as a sensor was proved by various analytical greenness scales.

A pregnant woman with severe aplastic anemia was managed using biweekly red blood cell transfusion and oral eltrombopag olamine administration during pregnancy. She was diagnosed with preeclampsia at 35 weeks of gestation. The severity of aplastic anemia is very important for predicting the course of pregnancy.