This disclosure provides a dosage regimen for co-administration of enzalutamide and a strong CYP3A4 inducer.

Provided herein are novel barbituric acid derivatives, their synthesis and use thereof in blocking leukocyte transmigration. The novel barbituric acid derivatives are useful for the treatment of disorders associated with leukocyte transmigration, such as for example inflammatory diseases and disorders, autoimmune diseases and disorders, and cancers.

The present invention relates to a lyophilized pharmaceutical composition of hydrolytically unstable pharmaceutical compounds, such as phenobarbital or salts thereof. The present invention also relates to an aqueous solution for injection of phenobarbital or salts thereof that is reconstituted from the lyophilized pharmaceutical composition. The pharmaceutical compositions of the present disclosure have an ethanol content in the range from about 5000 ppm to about 70000 ppm. The composition of the present disclosure, in certain embodiments, is stable following two years of storage, wherein the total impurities do not exceed 0.5%. The pharmaceutical compositions of the present disclosure may be used for the treatment of neonatal seizures.

The present invention relates to a lyophilized pharmaceutical composition of hydrolytically unstable pharmaceutical compounds, such as phenobarbital or salts thereof. The present invention also relates to an aqueous solution for injection of phenobarbital or salts thereof that is reconstituted from the lyophilized pharmaceutical composition. The pharmaceutical compositions of the present disclosure have an ethanol content in the range from about 5000 ppm to about 70000 ppm. The composition of the present disclosure, in certain embodiments, is stable following two years of storage, wherein the total impurities do not exceed 0.5%. The pharmaceutical compositions of the present disclosure may be used for the treatment of neonatal seizures.

The present invention features compounds useful in the treatment of neurological disorders and primary brain cancer. The compounds of the invention, alone or in combination with other pharmaceutically active agents, can be used for treating or preventing neurological disorders and primary brain cancer.

The present invention relates to the field of diseases or conditions that involve a pathologic level of RIPK1-dependent cell death. Specifically, the present invention refers to the use of the compound primidone or a pharmaceutically acceptable active metabolite, derivative, salt or solvate thereof for treating a disease or condition that involves a pathologic degree of RIPK1-dependent cell death. In a further aspect, the present invention provides a pharmaceutical composition comprising primidone or a pharmaceutically acceptable active metabolite, derivative, salt or solvate thereof for treating a disease or condition that involves a pathologic degree of RIPK1-dependent cell death.

Epileptic seizures are difficult to diagnose and are often difficult to distinguish from several conditions with similar presentations, and therefore, diagnosis of seizures is often a long, expensive, and unreliable process. This invention provides biomarkers for identifying seizures and epilepsy, assays for measuring and assessing biomarker concentration, predictive models based on biomarkers and computer systems for detecting, assessing and diagnosing phasic and tonic changes associated with seizures and epilepsy in all clinical and healthcare settings. Diagnostic methods, kits and predictive models provided herein provide quantitative and/or qualitative assessment in order to allow patients to proceed immediately to diagnostic and/or treatment protocols, and assess therapeutic treatment effectiveness.

Epileptic seizures are difficult to diagnose and are often difficult to distinguish from several conditions with similar presentations, and therefore, diagnosis of seizures is often a long, expensive, and unreliable process. This invention provides biomarkers for identifying seizures and epilepsy, assays for measuring and assessing biomarker concentration, predictive models based on biomarkers and computer systems for detecting, assessing and diagnosing phasic and tonic changes associated with seizures and epilepsy in all clinical and healthcare settings. Diagnostic methods, kits and predictive models provided herein provide quantitative and/or qualitative assessment in order to allow patients to proceed immediately to diagnostic and/or treatment protocols, and assess therapeutic treatment effectiveness.

The present disclosure provides methods of treating a tumor (e.g., renal cell cancer) by administering an immunotherapy comprising dendritic cells loaded with RNA encoding a tumor antigen and a pharmaceutical which can decrease circulating IgG levels, block IgG-mediated activation of CD16.sup.+ T cells, decrease the concentration and/or function of B cells, reduce the frequency of CD38.sup.+ TGF-β.sup.+ B cells, decrease B cell secretion of TGF-β, and/or sustain the frequency of CD25.sup.+CD28.sup.+ CD4 and/or CD8 T cells.

The present disclosure provides methods of treating a tumor (e.g., renal cell cancer) by administering an immunotherapy comprising dendritic cells loaded with RNA encoding a tumor antigen and a pharmaceutical which can decrease circulating IgG levels, block IgG-mediated activation of CD16.sup.+ T cells, decrease the concentration and/or function of B cells, reduce the frequency of CD38.sup.+ TGF-β.sup.+ B cells, decrease B cell secretion of TGF-β, and/or sustain the frequency of CD25.sup.+CD28.sup.+ CD4 and/or CD8 T cells.