Regorafenib: A comprehensive drug profile.

Regorafenib is a small molecule tyrosine kinase inhibitor administered orally drug, act by inhibiting the activity of the VEGF receptors. It is used for the treatment of patients with metastatic colorectal cancer (CRC), advanced gastrointestinal stromal tumors, and hepatocellular carcinoma. This comprehensive profile on regorafenib includes an original data as well as data collected from the literature on Profiles of Methods of Drug Synthesis, different Physical Drug Profiles, Drug Analytical methods and Pharmacological profile (ADME). This chapter is divided into five main sections: General Description of the drug, Physical Characteristics, Methods of Preparation, Methods of Analysis, Pharmacology and List of References. These main sections are further divided to many sub-titles to cover most aspect of the drug in the light of the available literature. Among these sub-titles are the formulae, Elemental Analysis, physical characteristics which include constant of ionization, solubility, X-ray powder diffraction pattern, TGA, thermal conduct and spectroscopic and stability. Additionally, analytical techniques including Electrochemical, Spectrophotometric and chromatographic methods, ADME profiles and pharmacological effects were also discussed. Furthermore, methods and schemes are outlined for the preparation of the drug substance.

Lapatinib: A comprehensive profile.

Lapatinib is an anticancer used for treatment of the patients with advanced metastatic breast cancer in conjunction with the chemotherapy drug capecitabine or with letrozole for the treatment of postmenopausal women with hormone receptor-positive metastatic breast cancer. This comprehensive profile of Lapatinib gives more detailed information about the description, formulae, Elemental Analysis, Uses and application. Furthermore, methods and schemes are outlined for the preparation of the drug substance. The physical properties of the medication include constant of ionization, solubility, X-ray powder diffraction pattern, differential scanning calorimetry, thermal conduct and spectroscopic studies are investigated. The methods employed in bulk medicines and/or in pharmaceutical formulations to analyze the drug substance include spectrophotometric, electrochemical and the chromatographic methods are indicated. Other studies on this drug substance include drug stability, pharmaceutical applications, mechanism of action, pharmacodynamics, and a dosing information are also reviewed.

Crizotinib: A comprehensive profile.

Crizotinib, approved in 2011, was the first approved inhibitor targeting anaplastic lymphoma kinase (ALK) It used for treatment of the patients with metastatic non-small cell lung cancer (NSCLC) that is anaplastic lymphoma kinase (ALK) positive. This chapter provides a complete review of crizotinib including nomenclature, physiochemical properties, methods of preparation, identification techniques and various qualitative and quantitative analytical techniques as well as pharmacology of crizotinib. In addition, the chapter also includes review of several methods for separation of crizotinib using chromatographic techniques.

The protective effect of losartan against sorafenib induced cardiotoxicity: Ex-vivo isolated heart and metabolites profiling studies in rat.

Sorafenib, a tyrosine kinase inhibitor that is used in the treatment of hepatocellular and renal cell carcinoma, was reported to induce cardiotoxicity. This study aimed to investigate the potential cardioprotective effect of losartan against sorafenib-induced cardiotoxicity in rat. Sorafenib significantly reduced the left ventricular pressure, heart rate dp/dt max & dp/dt min (indexes of myocardial contractility and relaxation; respectively), and prolonged both the systolic and diastolic periods. Coadminstration of losartan significantly reversed the effects of sorafenib on heart rate, dp/dt max and dp/dt min. In addition, there was a tendency for losartan to reverse sorafenib reduction in left ventricular pressure and perfusion pressure but it did not reach statistical significance. A GC-MS non-targeted based metabolites profiling of rat plasma revealed elevated metaboites, including urea and fatty acids levels, associated with sorafenib induced cardiotoxicity. However, only glycine and lactic acid were statistically significant. Interestingly, losartan co-administration with sorafenib restored these changes, and resulted in a significantly reduced glycine, urea and some fatty acids levels namely; Cis-vaccenic acid, oleic acid, stearic acid and undecanoic acid. In addition, based on histology results, losartan coadminitration almost obviated sorafenib-induced changes in cardiac tissues. The study suggests that losartan has the potential to exert a protective effect against sorafenib-induced cardiotoxicity.

Cigarette waste: Assessment of hazard to the environment and health in Riyadh city.

Cigarette waste/litter is considered a major environmental contamination problem worldwide as trillions of cigarettes are smoked worldwide and a large part of that, cigarette waste, is disposed of in the open areas including roads, parks, and streets, etc. cigarette litter is the most commonly found litter. It is mainly cigarette filter, made of cellulose acetate, and unburnt part of the tobacco filler. Filters from smoked cigarettes contain a significant amount of tar trapped in it. The tar contains thousands of chemicals and heavy metals. Both of these organic and inorganic constituents have been reported to be toxic to humans and cause a variety of diseases including inflammatory lung diseases, cardiovascular diseases, and cancers. Cigarette litter is a significant environmental concern as the chemicals and heavy metals can leach into the soil or water sources and pose threat to animals and plants, from there they can enter into the food chain as well. Several reports indicate toxicities to aquatic and terrestrial animals as they consumed cigarette litter. In the present investigation, cigarette litter was collected from 28 randomly selected locations in the Riyadh city to assess the risk to the environment. Cigarette litter, in the form of cigarette butts, was collected, counted, weighed and analyzed for heavy metal content. Data indicate the presence of a significant amount of cigarette litter on roadsides, streets, and parks in the Riyadh city. However, the investigation had its limitations as it did not focus on the absolute amount of cigarette litter vs the time. It also did not consider the amount of cigarette litter percent in the total waste discarded. The investigation presents the results of the screening of the cigarette litter present on the Riyadh city roads, streets, and parks. The findings raise concerns regarding the hazards the cigarette litter poses to the environment and human health. The investigation sheds the light on this unexplored aspect of smoking-associated issues in the Kingdom of Saudi Arabia.

Erlotinib.

Erlotinib (OSI-774), marketed by Genentech as Tarceva®, is anticancer drug approved by US-FDA for the treatment of Non-Small Cell Lung Cancer (NSCLC) and Pancreatic Cancer. Erlotinib inhibited epidermal growth factor receptor (EGFR) that blocks tumor cell division, produces cell cycle arrest, and initiates programmed cell death in EGFR-overexpressing human tumor cells. This study presents a comprehensive profile of erlotinib, including detailed nomenclature, formula, elemental analysis, methods of preparation, physico-chemical characteristics, and methods of analysis (including spectroscopic, electrochemical, and chromatographic methods of analysis). Spectroscopic and spectrometric analyses include UV/vis spectroscopy, vibrational spectroscopy, nuclear magnetic resonance spectrometry ((1)H and (13)C NMR), and mass spectrometry. Chromatographic methods of analyses include thin layer chromatography, and high-performance liquid chromatography. Pharmacology of erlotinib including pharmacodynamics, mechanism of action, pharmacokinetics and drug-drug interactions were also presented. An appropriate table and figures were attached to each of the above mentioned sections along with total of 48 references.

Sorafenib.

Sorafenib (BAY-43-9006), marketed by Bayer as Nexavar® (USA), is anticancer drug approved by US-FDA for the treatment of unresectable hepatocellular carcinoma and advanced renal cell carcinoma. Sorafenib inhibited tumor growth and angiogenesis through targeting both the RAF/MEK/ERK pathway and receptor tyrosine kinases. This study presents a comprehensive profile of sorafenib, including detailed nomenclature, formula, elemental analysis, methods of preparation, physico-chemical characteristics, and methods of analysis (including spectroscopic, electrochemical, and chromatographic methods of analysis). Spectroscopic and spectrometric analyses include UV/vis spectroscopy, vibrational spectroscopy, nuclear magnetic resonance spectrometry ((1)H and (13)C NMR), and mass spectrometry. Chromatographic methods of analyses include thin layer chromatography and high-performance liquid chromatography. Only few stability indicating methods were found for quantification of sorafenib after exposing tablet dosage form to various stress conditions such as hydrolysis, oxidation, thermal stress, photo and UV light. However, none of these described methods were made to separate and quantify the degradation products. Pharmacology studies including pharmacodynamics, mechanism of action, pharmacokinetics and drug-drug interactions were also presented. An appropriate table and figures were attached to each of the above mentioned sections along with total of 55 references.

Dasatinib significantly reduced in vivo exposure to cyclosporine in a rat model: The possible involvement of CYP3A induction.

BACKGROUND: This study was designed to investigate the effects of dasatinib and nilotinib on the pharmacokinetics of cyclosporine in rats, as these drugs have been reported to be cytochrome P450 3A4 (CYP3A4) substrates. METHODS: Control and test groups (n = 5) were treated with vehicle and dasatinib (4 mg/kg, and 16 mg/kg, oral) or nilotinib (94 mg/kg, oral), respectively, for 8 consecutive days. On day 8, all groups were administered cyclosporine (30 mg/kg) 1 h after the last dose of dasatinib or nilotinib. Blood was collected from the retro-orbital plexus in heparinized tubes at different time points (0, 0.5, 1, 1.5, 2, 3.5, 8, 12, and 24 h). The cyclosporine concentration in blood samples was determined by ultra-performance liquid chromatography-tandem mass spectrometry. The effects of dasatinib on CYP3A2 mRNA and protein expression levels were also investigated. RESULTS: Dasatinib significantly reduced the maximum blood concentration (Cmax) of cyclosporine by 85.7%, and increased hepatic and intestinal CYP3A2 mRNA and protein expression levels by 2.4- and 1.25-fold, respectively, compared to those in the controls (p < 0.05). On the other hand, nilotinib had no significant effects on cyclosporine pharmacokinetic parameters. CONCLUSIONS: Dasatinib significantly reduced cyclosporine exposure, which was most probably related to the induction of CYP3A-mediated cyclosporine metabolism.