In addition to its cytotoxic, antimitotic-based mechanisms, preclinical studies in human breast cancer models have shown that eribulin also exerts complex effects on the biology of surviving cancer cells and residual tumors that appear unrelated to its antimitotic effects. These non-mitotic mechanisms include vascular remodeling that leads to increased tumor perfusion and mitigation of tumor hypoxia, phenotypic changes consistent with reversal of epithelial-mesenchymal transition (EMT), and decreased capacity for migration and invasion leading to reduced metastatic capacity as measured in a preclinical experimental metastasis model. In other studies, eribulin treatment of leiomyosarcoma and liposarcoma cells leads to increased expression of smooth muscle and adipocyte differentiation antigens, respectively. Taxane-resistant cancers are often unresponsive to eribulin. A recent study found that this resistance is due to expression of multidrug resistance protein 1 (MDR1). Fluorescently labeled eribulin has been used to study the pharmacokinetics and pharmacodynamics at single cell level in vivo.The synthesis of eribulin was first published in 2001; a new synthetic route to the drug was published in 2009. Clinical trials
Eribulin is being investigated for use in a variety of other solid tumors, including breast cancer, non-small cell lung cancer, prostate cancer, brain cancer, cervical cancer, urothelial cancer, melanoma, solitary fibrous tumors, and various sarcomas. Research and development
Two new eribulin based products are in the research and development phase; a liposomal formulation and antibody drug combination therapy, both are for the treatment of solid tumors. The liposomal formulation of eribulin, E7389 liposomal, is currently in Phase I clinical trials.
Aspirin/paracetamol(acetaminophen)/caffeine is a combination drug for the treatment of pain, especially tension headache and migraine. It is sold in the US under the trade names Goodys Powder and Excedrin, although not all products sold under the Excedrin brand contain this combination. It is sold in the UK under various brandnames including Anadin Extra. Adverse effects
The recommended dosing has a low risk profile when taken occasionally in a well hydrated state. As with all medications containing paracetamol (acetaminophen), concomitant use with alcohol carries a significant risk of hepatotoxicity. The combination of paracetamol with aspirin also creates the risk of renal papillary necrosis if large doses are taken chronically. This is because paracetamol yields a toxic metabolite that can accumulate in the kidney while aspirin works to deplete the glutathione stores necessary to oxidize it. Additionally, chronic aspirin usage is associated with increased risk of gastrointestinal bleeding. Chemical detection
The combination of these three compounds can be detected in pharmaceutical formulations, urine and blood serum in trace quantities using electrochemical methods. Other trade names
The combination was introduced in 1950, sold as the name Triagesic.