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Pharmaceutical Research (pharmaceutical + research)
Terms modified by Pharmaceutical Research Selected AbstractsPostmarketing drug dosage changes of 499 FDA-approved new molecular entities, 1980,1999,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 6 2002James Cross MS Abstract Purpose Risks and benefits of marketed drugs can be improved by changing their labels to optimize dosage regimens for indicated populations. Such postmarketing label changes may reflect the quality of pre-marketing development, regulatory review, and postmarketing surveillance. We documented dosage changes of FDA-approved new molecular entities (NMEs), and investigated trends over time and across therapeutic groups, on the premise that improved drug development methods have yielded fewer postmarketing label changes over time. Methods We compiled a list of NMEs approved by FDA from 1 January 1980 to 31 December 1999 using FDA's website, Freedom of Information Act request, and PhRMA (Pharmaceutical Research and Manufacturers of America) database. Original labeled dosages and indicated patient populations were tracked in labels in the Physician's Desk Reference®. Time and covariate-adjusted risks for dosage changes by 5-year epoch and therapeutic groups were estimated by survival analysis. Results Of 499 NMEs, 354 (71%) were evaluable. Dosage changes in indicated populations occurred in 73 NMEs (21%). A total of 58 (79%) were safety-motivated, net dosage decreases. Percentage of NMEs with changes by therapeutic group ranged from 27.3% for neuropharmacologic drugs to 13.6% for miscellaneous drugs. Median time to change following approval fell from 6.5 years (1980,1984) to 2.0 years (1995,1999). Contrary to our premise, 1995,1999 NMEs were 3.15 times more likely to change in comparison to 1980,1984 NMEs (p,=,0.008, Cox analysis). Conclusions Dosages of one in five NMEs changed, four in five changes were safety reductions. Increasing frequency of changes, independent of therapeutic group, may reflect intensified postmarketing surveillance and underscores the need to improve pre-marketing optimization of dosage and indicated population. Copyright © 2002 John Wiley & Sons, Ltd. [source] Analysis of unstirred water layer in in vitro permeability experimentsJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 12 2009Timo Korjamo Abstract In vitro permeability experiments are used widely in drug discovery and other areas of pharmaceutical research. Much effort has been expended in developing novel epithelial models but generally much less attention has been paid to the hydrodynamic barrier in the actual experiments. The restricted liquid flow in the vicinity of solid surfaces leads to a zone where the diffusional movement of molecules exceeds the convection. This leads to formation of a concentration gradient between the bulk solution and the surface. The formed unstirred water layer (UWL) reduces the apparent permeability (Papp) of compounds that rapidly pass through the actual epithelial layer. This lowers the resolution of Papp versus fraction-absorbed assay, complicates the structure-permeability analysis and skews apparent kinetic parameters of transporter substrates. This review describes the techniques that can be used to determine the UWL thickness in permeability experiments and apparatuses described in the literature to control the in vitro hydrodynamics. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:4469,4479, 2009 [source] Recent pharmaceutical applications of raman and terahertz spectroscopiesJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 11 2008Cushla M. McGoverin Abstract This review outlines recent applications of Raman and terahertz spectroscopies within the field of pharmaceutical research. Of the two approaches, Raman is better established and more accessible, and is responsible for the majority of reviewed studies. Both techniques feature limitations, however, which are discussed in the context of methods used to circumvent apparent restrictions. Regardless, the diverse range of applications illustrates the flexibility of Raman and terahertz spectroscopies when characterizing pharmaceutical systems. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:4598,4621, 2008 [source] In-vitro and in-vivo studies of cefpirom using bile salts as absorption enhancersJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 12 2003Yahya Mrestani ABSTRACT Cephalosporins have to be administered by injection because of the poor intestinal absorption of the orally delivered drugs. Because of the obvious drawbacks of drug delivery by injection, the development of alternatives with enhanced oral bioavailability is receiving much attention in pharmaceutical research. Cefpirom (Cp) is a new semi-synthetic amino-2-thiazolyl-methoxyimino cephalosporin that has been substituted in position 3 with a cyclopenteno-pyridinium group in order to create a zwitterionic compound. It exhibits highly hydrophilic properties, as shown from its extremely low partition coefficient, and therefore its lipophilicity was increased using bile salts. The effect of this on the partition coefficients determined in the n-octanol/buffer system was confirmed using an in-vitro transport model with artificial and biological membranes. The pharmacokinetic properties of Cp were investigated in rabbits after intraduodenal administration with and without bile salts. Furthermore, the physiological compatibility of the bile salts was investigated using active D-glucose transport. [source] Peak shape improvement of basic analytes in capillary liquid chromatographyJOURNAL OF SEPARATION SCIENCE, JSS, Issue 3 2005Anja Prüß Abstract The analysis of bases is of special interest in pharmaceutical research because numerous active substances contain basic functional groups. Capillary and conventional size LC separations of drug substances spiked with potential impurities were compared. In the case of the nonpolar drug levonorgestrel equal separation efficiency was readily attained by both techniques. The peaks of basic substances, however, showed extensive tailing when separated by capillary LC. The peak deformation was attributable to interactions of the basic substances with the polar inner surface of the fused silica capillaries employed in capillary LC and does not appear with the steel tubing generally used in conventional size LC. This drawback of capillary LC was overcome by use of deactivated fused silica capillaries for column hardware and transfer lines. [source] MRI in ocular drug deliveryNMR IN BIOMEDICINE, Issue 9 2008S. Kevin Li Abstract Conventional pharmacokinetic methods for studying ocular drug delivery are invasive and cannot be conveniently applied to humans. The advancement of MRI technology has provided new opportunities in ocular drug-delivery research. MRI provides a means to non-invasively and continuously monitor ocular drug-delivery systems with a contrast agent or compound labeled with a contrast agent. It is a useful technique in pharmacokinetic studies, evaluation of drug-delivery methods, and drug-delivery device testing. Although the current status of the technology presents some major challenges to pharmaceutical research using MRI, it has a lot of potential. In the past decade, MRI has been used to examine ocular drug delivery via the subconjunctival route, intravitreal injection, intrascleral injection to the suprachoroidal space, episcleral and intravitreal implants, periocular injections, and ocular iontophoresis. In this review, the advantages and limitations of MRI in the study of ocular drug delivery are discussed. Different MR contrast agents and MRI techniques for ocular drug-delivery research are compared. Ocular drug-delivery studies using MRI are reviewed. Copyright © 2008 John Wiley & Sons, Ltd. [source] In Vivo mouse imaging and spectroscopy in drug discoveryNMR IN BIOMEDICINE, Issue 3 2007Nicolau Beckmann Abstract Imaging modalities such as micro-computed tomography (micro-CT), micro-positron emission tomography (micro-PET), high-resolution MRI, optical imaging, and high-resolution ultrasound have become invaluable tools in preclinical pharmaceutical research. They can be used to non-invasively investigate, in vivo, rodent biology and metabolism, disease models, and pharmacokinetics and pharmacodynamics of drugs. The advantages and limitations of each approach usually determine its application, and therefore a small-rodent imaging laboratory in a pharmaceutical environment should ideally provide access to several techniques. In this paper we aim to illustrate how these techniques may be used to obtain meaningful information for the phenotyping of transgenic mice and for the analysis of compounds in murine models of disease. Copyright © 2007 John Wiley & Sons, Ltd. [source] Versatile protein microarray based on carbohydrate-binding modulesPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 7 2005Keren Ofir Abstract Non-DNA microarrays, such as protein, peptide and small molecule microarrays, can potentially revolutionize the high-throughput screening tools currently used in basic and pharmaceutical research. However, fundamental obstacles remain that limit their rapid and widespread implementation as an alternative bioanalytical approach. These include the prerequisite for numerous proteins in active and purified form, ineffectual immobilization strategies and inadequate means for quality control of the considerable numbers of multiple reagents. This study describes a simple yet efficient strategy for the production of non-DNA microarrays, based on the tenacious affinity of a carbohydrate-binding module (CBM) for its three-dimensional substrate, i.e., cellulose. Various microarray formats are described, e.g., conventional and single-chain antibody microarrays and peptide microarrays for serodiagnosis of human immunodeficiency virus patients. CBM-based microarray technology overcomes many of the previous obstacles that have hindered fabrication of non-DNA microarrays and provides a technically simple but effective alternative to conventional microarray technology. [source] Patents and Pharmaceutical R&D: Consolidating Private,Public Partnership Approach to Global Public Health CrisesTHE JOURNAL OF WORLD INTELLECTUAL PROPERTY, Issue 4 2010Chidi Oguamanam Intellectual property (IP) is a reward and incentive market-driven mechanism for fostering innovation and creativity. The underlying, but disputed, assumption to this logic is that without IP, the wheel of innovation and inventiveness may grind to a halt or spin at a lower and unhelpful pace. This conventional justification of IP enjoys, perhaps, greater empirical credibility with the patent regime than with other regimes. Despite the inconclusive role of patents as a stimulant for research and development (R&D), special exception is given to patent's positive impact on innovation and inventiveness in the pharmaceutical sector. This article focuses on that sector and links the palpable disconnect between the current pharmaceutical R&D agenda and global public health crises, especially access to drugs for needy populations, to a flaw in the reward and incentive theory of the patent system. It proposes a creative access model to the benefits of pharmaceutical research by pointing in the direction of a global treaty to empower and institutionalize private,public partnerships in health care provisions. Such a regime would restore balance in the global IP system that presently undermines the public-regarding considerations in IP jurisprudence. [source] Agreement on Trade-Related Aspects of Intellectual Property Rights and Access to Medication: Does Egypt Have Sufficient Safeguards Against Potential Public Health Implications of the AgreementTHE JOURNAL OF WORLD INTELLECTUAL PROPERTY, Issue 1 2010Heba Wanis The implementation of the Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS Agreement) in Egypt raised concerns over public health implications, resulting from pharmaceutical patents, especially because the Egyptian pharmaceutical industry is heavily dependent on generic production. The current level of global competition in the pharmaceutical market, together with the lack of local pharmaceutical research, threaten the industry, and, as a result, access to affordable medication is expected to be impaired. Determinants of access to medicines are analysed. An epidemiological overview of the most prevalent diseases in Egypt has been done in light of the results of surveys about changes in medicine prices and availability, to speculate about potential limitations in access to medicines. Considering domestic pharmaceutical pricing and marketing regulations, which are mainly concerned with affordability, together with the flexibilities in the TRIPS Agreement, short-term solutions to potential access problems will be possible. Egypt has the necessary theoretical safeguards against negative implications of the TRIPS Agreement on access to treatment. However, this does not necessarily mean that these safeguards will be implemented in a way that will protect against the implications of patent protection on medicines in the long term. [source] An integrated database of flavonoidsBIOFACTORS, Issue 3 2006Takashi Kinoshita Abstract Flavonoids are polyphenolic compounds that occur ubiquitously in foods of plant origin. Some of these molecules exhibit various physiological activities. Among existing drugs, there are a huge number of compounds bearing a flavonoid-related skeleton. Because of the relevance for pharmaceutical research, it would be beneficial to collect these compounds into a database. Recently, various databases of chemicals were compiled to help biological and/or chemical research, but no comprehensive database of flavonoids with chemical structures and physicochemical parameters, supposedly related to their activity, is available yet. The aim of this research was to merge the information about flavonoids of plant origin and flavonoids used as medicines into a database. Moreover, predictions of activities against various targets were performed using a virtual screening procedure to demonstrate a possible application of the database for pharmaceutical research. [source] Study of nobiletin binding to bovine serum albumin by capillary electrophoresis,frontal analysis and circular dichroismBIOMEDICAL CHROMATOGRAPHY, Issue 9 2010Lian Yi Abstract A very recent epidemiological study provided strong support for nobiletin (NOB) as a potential candidate chemopreventive agent against cancer. From the pharmacology point of view, drug,protein interactions are determining factors in therapeutic, pharmacodynamic and toxicological drug properties. In this work, for the first time, detection of NOB at near-physiological conditions was accomplished by means of capillary electrophoresis,frontal analysis (CE-FA), and then the binding constants of NOB with bovine serum albumin (BSA) at the same conditions were determined. Complexation of NOB,BSA led to a decrease of the height for free NOB with increasing concentration of BSA. These results revealed the presence of a single class of binding site on BSA, and provided the binding constant of 103/m, showing the strong affinity of NOB for BSA. Furthermore, circular dichroism spectra showed that, when the molar ratio of NOB to BSA was up to 2:1, NOB did not affect the overall protein conformation significantly and the protein thus retained a native-like structure. These results may provide important information for preclinical studies of nobiletin in pharmaceutical research. Copyright © 2010 John Wiley & Sons, Ltd. [source] Integrated Sampling Procedure for Metabolome AnalysisBIOTECHNOLOGY PROGRESS, Issue 5 2006Jochen Schaub Metabolome analysis, the analysis of large sets of intracellular metabolites, has become an important systems analysis method in biotechnological and pharmaceutical research. In metabolic engineering, the integration of metabolome data with fluxome and proteome data into large-scale mathematical models promises to foster rational strategies for strain and cell line improvement. However, the development of reproducible sampling procedures for quantitative analysis of intracellular metabolite concentrations represents a major challenge, accomplishing (i) fast transfer of sample, (ii) efficient quenching of metabolism, (iii) quantitative metabolite extraction, and (iv) optimum sample conditioning for subsequent quantitative analysis. In addressing these requirements, we propose an integrated sampling procedure. Simultaneous quenching and quantitative extraction of intracellular metabolites were realized by short-time exposure of cells to temperatures ,95 °C, where intracellular metabolites are released quantitatively. Based on these findings, we combined principles of heat transfer with knowledge on physiology, for example, turnover rates of energy metabolites, to develop an optimized sampling procedure based on a coiled single tube heat exchanger. As a result, this sampling procedure enables reliable and reproducible measurements through (i) the integration of three unit operations into a one unit operation, (ii) the avoidance of any alteration of the sample due to chemical reagents in quenching and extraction, and (iii) automation. A sampling frequency of 5 s,1 and an overall individual sample processing time faster than 30 s allow observing responses of intracellular metabolite concentrations to extracellular stimuli on a subsecond time scale. Recovery and reliability of the unit operations were analyzed. Impact of sample conditioning on subsequent IC-MS analysis of metabolites was examined as well. The integrated sampling procedure was validated through consistent results from steady-state metabolite analysis of Escherichia coli cultivated in a chemostat at D = 0.1 h,1. [source] | ||||||||||||||||