Clinical Drug Development

Tumor tissue biomarkers are the basis for targeted therapy in non small-cell lung cancer (NSCLC). These biomarkers either reflect the target of the specific drug or some factor that might abrogate the effect of the drug. These targeted drugs are small-molecule inhibitors of a specific tyrosine kinase or a monoclonal antibody against a specific recep- tor. In this review, tissue biomarkers in NSCLC and com- panion diagnostics will be described, followed by an overview of targeted therapy to EGF/EGFR, HER2, VEGF/VEGFR, ALK, KRAS, BRAF, MEK and MET and some of the newer potential targets. Recent initiatives include the Lung Cancer Matrix Network, the BATTLE trials and the Lung Cancer Mutation Consortium. There are a number of key clinical trials in targeted therapy in NSCLC which will be reporting during the next year.

Emesis, also known as nausea and vomiting, are common symptoms associated with ingestion of toxicants, drug side effects, advanced terminal diseases such as cancer and postoperative procedures. Emesis is mediated through the coordinated
action of central and peripheral regulatory centres that involve receptors including dopamine Type 2, serotonin, muscarinic cholinergic, histamine, cannabinoids and NK-1 receptors. Many anti-emetic drugs targeting these receptors are currently in
use but they also cause undesirable side effects such as excessive sedation, hypotension,dry mouth, dysphoria, hallucinations and extrapyramidal signs. This review highlights the pharmacological mechanism of emesis and current antiemtic drugs
together with detailed analysis of in vitro and in vivo anti-emetic bioassay models. The pharmacology of crude natural products extracts and purified anti-emeticcompounds (cannabinoids, chalcones, diarylheptanoids, flavonoids, hydroxycinnamic
acids, lignans, phenylpropanoids, polysaccharides, saponins, terpenes and glycosidic derivatives) are also systematically presented with their mechanism of action. The potential of natural products as sources of new clinically proven anti-emetic drugs are discussed.

... JL Marenco,1 M. Pérez,2 FJ Navarro,3 FG Martínez,4 J. Beltrán,5 D ... 1 Hospital Universitario de Valme, Seville, Spain 2 Complejo Hospitalario 'Carlos Haya', Malaga, Spain 3 Hospital General Universitario de Elche, Alicante, Spain 4 Hospital Universitario Reina Sofia, Cordoba ...

Amisulpride is an atypical antipsychotic with a significantly greater effect size than first-generation, typical antipsychotics, and efficacy at least similar to that of olanzapine and risperidone in large-scale clinical trials in schizophrenia. Amisulpride provides greater improvement in positive and negative symptoms of schizophrenia, a better long-term outcome than typical antipsychotics, and distinct tolerability advantages over typical antipsychotics, which are reported to cause extrapyramidal symptoms (EPS) in 20-50% of patients. In addition, amisulpride is associated with significantly less weight gain than olanzapine and risperidone, does not increase body mass index, and favourably influences lipid profiles. In many patients with schizophrenia, adverse events impair adherence to treatment, and switching from typical or atypical antipsychotic therapy to amisulpride may be clinically appropriate. Observational drug-utilization studies suggest that many physicians switch to am...

An intravenous (IV) formulation of esomeprazole has been developed as an alternative to oral administration. To meet the needs of different clinical situations it would be preferable if an IV dose could be administered as either an injection or an infusion, while producing similar effects. To compare the effects of IV esomeprazole 40mg given as a 3-minute injection or a 30-minute infusion on intragastric pH during single and repeated once-daily dosing in healthy subjects. In this single-centre, double-blind, double-dummy, randomised, two- way crossover study, subjects were randomised to receive either a 3-minute IV injection or a 30-minute IV infusion of esomeprazole 40mg. Both regimens were given once daily for 10 days. After a washout period of at least 13 days, subjects were crossed over to the other treatment. Intragastric pH monitoring was performed on days 1 and 10. Blood samples were also taken throughout days 1 and 10. Data were available from 41 subjects. Time with intragas...

Abstract: Exaptation is process that is characterised by evolution of characteristics, its evolution for other usages, and later co-opted for their current role. In pharmaceutical industry, innovations have high potential in terms of competitive advantage and profit, but are also connected with high risks associated with costs, time and uncertainty. In order to minimize risks, companies are frequently choosing strategy of exaptation in terms of redeveloping compound for use in a different disease. Intention of this research is to provide analysis and quantification (measurement) of drugs that have been exaptated through process of drug reposition. Results indicates that on level of 6098 clinical studies Phase I we have observed total of 659 drugs/substances  (~11%) that have been used in more than one clinical research for the same or different indication showing level of exaptation use in clinical research.
Keywords: exaptation, drug reposition, pharmaceutical industry, innovation, pharmacoeconomics, research and development