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Eli Lilly and Company is an American global pharmaceutical company with headquarters located in Indianapolis, Indiana, in the United States. The company also has offices in Puerto Rico and 17 other countries. Their products are sold in approximately 125 countries. The company was founded in 1876 by Col. Eli Lilly, a pharmaceutical chemist and veteran of the American Civil War, after whom the company was named.Among other specialties, Lilly was the first company to mass-produce penicillin, the Salk polio vaccine, and insulin, including one of the first pharmaceutical companies to produce human insulin using recombinant DNA. Lilly is also the world's largest manufacturer and distributor of psychiatric medications. In 2009, Eli Lilly pleaded guilty to illegally marketing the drug Zyprexa for off-label uses not approved by the U.S. Food and Drug Administration, particularly the treatment of dementia in the elderly. The company paid a $515 million criminal fine, at the time the largest in history. Wikipedia.

Drugs that covalently bond to their biological targets have a long history in drug discovery. A look at drug approvals in recent years suggests that covalent drugs will continue to make impacts on human health for years to come. Although fraught with concerns about toxicity, the high potencies and prolonged effects achievable with covalent drugs may result in less-frequent drug dosing and in wide therapeutic margins for patients. Covalent inhibition can also dissociate drug pharmacodynamics (PD) from pharmacokinetics (PK), which can result in desired drug efficacy for inhibitors that have short systemic exposure. Evidence suggests that there is a reduced risk for the development of resistance against covalent drugs, which is a major challenge in areas such as oncology and infectious disease. ©2015 Elsevier Ltd. All rights reserved. .

Salts of active pharmaceutical ingredients are often used to enhance solubility, dissolution rate, or take advantage of other improved solid-state properties. The selected form must be maintained during processing and shelf-life to ensure quality. We aimed to develop a model to quantify risk of disproportionation, where the salt dissociates back to the freebase form. A mechanistic model based on thermodynamics was built to predict disproportionation. Stress testing of molecules in combination with excipients was used to benchmark model predictions. X-ray powder diffraction and solid-state NMR were used to quantify the formation of freebase experimentally. 13 pharmaceutical compounds were screened in 4 formulations containing different combinations of excipients. The test set spanned molecules which did and did not disproportionate and also formulations which did and did not induce disproportionation. Model predictions were in qualitative agreement with the experimental data, recovering trends of how disproportionation varies with humidity, formulation excipients, base pK(a) and solubility of the API. The model can predict the balance between different driving forces for disproportionation with limited experimental data resulting in a tool to aid in early-phase risk assessment and formulation design with respect to disproportionation.

Moller D.E.,Eli Lilly and Company
Cell Metabolism | Year: 2012

Despite the advent of new drug classes, the global epidemic of cardiometabolic disease has not abated. Continuing unmet medical needs remain a major driver for new research. Drug discovery approaches in this field have mirrored industry trends, leading to a recent increase in the number of molecules entering development. However, worrisome trends and newer hurdles are also apparent. The history of two newer drug classes - glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors - illustrates both progress and challenges. Future success requires that researchers learn from these experiences and continue to explore and apply new technology platforms and research paradigms. © 2012 Elsevier Inc.

Bushe C.J.,Eli Lilly and Company
Journal of psychopharmacology (Oxford, England) | Year: 2010

Over the last five years, large data sets on mortality in schizophrenia have been published which have established mortality as a measurable clinical endpoint. Four issues need clarification: whether mortality rates are declining, what the causes of death are, the effects antipsychotic treatments have on mortality and whether these data inform as to how mortality may be reduced in the future. A PubMed search was carried out to identify relevant publications. The search strategy was conducted as a review focusing predominantly on data since 2006. A large number of retrospective epidemiological and prospective studies have been published on mortality rates and causation in schizophrenia, predominantly from 2006-2009. Data suggest that the mortality gap with the general population increased from the 1970s but may have peaked in the mid-1990s. The main causes of mortality are suicide, cancer and cardiovascular disease, with evidence that cancer mortality rates are similar to cardiovascular mortality rates. Mortality causation is dependent upon age of the cohort, length of follow up and type of study. Antipsychotic treatments reduce mortality when compared with no treatment and atypical antipsychotics do not appear to increase cardiovascular mortality and morbidity compared with conventionals; further research is required for any definitive conclusion.

Purpose: Peripheral neuropathy (PN) is an identified risk of systemic antibacterial therapy with fluoroquinolones. The risk and its severity, including the development of Guillain-Barré syndrome (GBS) between individual agents is uncertain. This study examines the association between fluoroquinolones and PN and GBS in cases spontaneously reported to the FDA Adverse Event Reporting System. Methods: Cases reported to FDA Adverse Event Reporting System between 1997 and 2012 were retrieved. The Medical Dictionary for Regulatory Activities Preferred Term was used to define PN and GBS. Individual fluoroquinolones were identified by generic names and route of administration. Empirical Bayes Geometric Mean (EBGM) with 95% confidence interval (EB05-EB95) was calculated as disproportionality measure. Safety signals with EB05 2 or more was considered a significant disproportional increase in the event reporting of at least twice times higher than that expected. Results: There were 539 PN reports out of 46,257 adverse event reports submitted for fluoroquinolones. Nine percent of PN reports were for GBS. Significant disproportionality of PN (EBGM 2.70; EB05-EB95 2.51-2.90) and GBS (EBGM 3.22; EB05-EB95 2.55-4.02) was identified for fluoroquinolones. Signals of PN were detected for ciprofloxacin (EBGM 3.24; EB05-EB95 2.87-3.66) and levofloxacin (EBGM 3.36; EB05-EB95 3.02-3.72). A GBS signal was detected for ciprofloxacin (EBGM 4.15; EB05-EB95 2.94-5.74). GBS and PN, respectively, ranked 6th and 8th among reported neurologic events. Conclusions: This study re-emphasizes the link between fluoroquinolones and PN and shows the potential association with more severe forms of nerve damage, for example, GBS. Unless the benefit of fluoroquinolone therapy (e.g., overwhelming infection or development of bacterial resistance) outweighs PN risk, treatment with alternative antibacterial agents is recommended. © 2014 Elsevier Inc.

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