WorldWideScience

Sample records for rapid drug absorption

  1. Rapidly variable relatvistic absorption

    Science.gov (United States)

    Parker, M.; Pinto, C.; Fabian, A.; Lohfink, A.; Buisson, D.; Alston, W.; Jiang, J.

    2017-10-01

    I will present results from the 1.5Ms XMM-Newton observing campaign on the most X-ray variable AGN, IRAS 13224-3809. We find a series of nine absorption lines with a velocity of 0.24c from an ultra-fast outflow. For the first time, we are able to see extremely rapid variability of the UFO features, and can link this to the X-ray variability from the inner accretion disk. We find a clear flux dependence of the outflow features, suggesting that the wind is ionized by increasing X-ray emission.

  2. Mechanistic Approaches to Predicting Oral Drug Absorption

    OpenAIRE

    Huang, Weili; Lee, Sau Lawrence; Yu, Lawrence X.

    2009-01-01

    Modeling and simulation of oral drug absorption have been widely used in drug discovery, development, and regulation. Predictive absorption models are used to determine the rate and extent of oral drug absorption, facilitate lead drug candidate selection, establish formulation development strategy, and support the development of regulatory policies. This review highlights the development of recent drug absorption models including dispersion and compartmental models. The compartmental models i...

  3. Rapidly separating microneedles for transdermal drug delivery.

    Science.gov (United States)

    Zhu, Dan Dan; Wang, Qi Lei; Liu, Xu Bo; Guo, Xin Dong

    2016-09-01

    The applications of polymer microneedles (MNs) into human skin emerged as an alternative of the conventional hypodermic needles. However, dissolving MNs require many minutes to be dissolved in the skin and typically have difficulty being fully inserted into the skin, which may lead to the low drug delivery efficiency. To address these issues, we introduce rapidly separating MNs that can rapidly deliver drugs into the skin in a minimally invasive way. For the rapidly separating MNs, drug loaded dissolving MNs are mounted on the top of solid MNs, which are made of biodegradable polylactic acid which eliminate the biohazardous waste. These MNs have sufficient mechanical strength to be inserted into the skin with the drug loaded tips fully embedded for subsequent dissolution. Compared with the traditional MNs, rapidly separating MNs achieve over 90% of drug delivery efficiency in 30s while the traditional MNs needs 2min to achieve the same efficiency. With the in vivo test in mice, the micro-holes caused by rapidly separating MNs can heal in 1h, indicating that the rapidly separating MNs are safe for future applications. These results indicate that the design of rapidly separating dissolvable MNs can offer a quick, high efficient, convenient, safe and potentially self-administered method of drug delivery. Polymer microneedles offer an attractive, painless and minimally invasive approach for transdermal drug delivery. However, dissolving microneedles require many minutes to be dissolved in the skin and typically have difficulty being fully inserted into the skin due to the skin deformation, which may lead to the low drug delivery efficiency. In this work we proposed rapidly separating microneedles which can deliver over 90% of drug into the skin in 30s. The in vitro and in vivo results indicate that the new design of these microneedles can offer a quick, high efficient, convenient and safe method for transdermal drug delivery. Copyright © 2016 Acta Materialia Inc

  4. Absorption sites of orally administered drugs in the small intestine.

    Science.gov (United States)

    Murakami, Teruo

    2017-12-01

    In pharmacotherapy, drugs are mostly taken orally to be absorbed systemically from the small intestine, and some drugs are known to have preferential absorption sites in the small intestine. It would therefore be valuable to know the absorption sites of orally administered drugs and the influencing factors. Areas covered:In this review, the author summarizes the reported absorption sites of orally administered drugs, as well as, influencing factors and experimental techniques. Information on the main absorption sites and influencing factors can help to develop ideal drug delivery systems and more effective pharmacotherapies. Expert opinion: Various factors including: the solubility, lipophilicity, luminal concentration, pKa value, transporter substrate specificity, transporter expression, luminal fluid pH, gastrointestinal transit time, and intestinal metabolism determine the site-dependent intestinal absorption. However, most of the dissolved fraction of orally administered drugs including substrates for ABC and SLC transporters, except for some weakly basic drugs with higher pKa values, are considered to be absorbed sequentially from the proximal small intestine. Securing the solubility and stability of drugs prior to reaching to the main absorption sites and appropriate delivery rates of drugs at absorption sites are important goals for achieving effective pharmacotherapy.

  5. Mathematical models for dermal drug absorption.

    Science.gov (United States)

    Selzer, Dominik; Neumann, Dirk; Schaefer, Ulrich F

    2015-01-01

    Mathematical models of dermal transport offer the advantages of being much faster and less expensive than in vitro or in vivo studies. The number of methods used to create such models has been increasing rapidly, probably due to the steady rise in computational power. Although each of the various approaches has its own virtues and limitations, it may be difficult to decide which approach is best suited to address a given problem. Here we outline the basic ideas, drawbacks and advantages of compartmental and quantitative structure-activity relationship models, as well as of analytical and numerical approaches for solving the diffusion equation. Examples of special applications of the different approaches are given. Although some models are sophisticated and might be used in future to predict transport through damaged or diseased skin, the comparatively low availability of suitable and accurate experimental data limits extensive usage of these models and their predictive accuracy. Due to the lack of experimental data, the possibility of validating mathematical models is limited.

  6. Drug gastrointestinal absorption in rat: Strain and gender differences.

    Science.gov (United States)

    Oltra-Noguera, Davinia; Mangas-Sanjuan, Victor; González-Álvarez, Isabel; Colon-Useche, Sarin; González-Álvarez, Marta; Bermejo, Marival

    2015-10-12

    Predictive animal models of intestinal drug absorption are essential tools in drug development to identify compounds with promising biopharmaceutical properties. In situ perfusion absorption studies are routinely used in the preclinical setting to screen drug candidates. The objective of this work is to explore the differences in magnitude and variability on intestinal absorption associated with rat strain and gender. Metoprolol and Verapamil absorption rate coefficients were determined using the in situ closed loop perfusion model in four strains of rats and in both genders. Strains used were Sprague-Dawley, Wistar-Han, Wistar-Unilever, Long-Evans and CD∗IGS. In the case of Metoprolol only CD∗IGS and Wistar Unilever showed differences between males and females. For Verapamil, Wistar Han and Sprague-Dawley strains do not show differences between male and female rats. That means that in these strains permeability data from male and female could be combined. In male rats, which are commonly used for permeability estimation, there were differences for Metoprolol permeability between Sprague-Dawley (with lower permeability values) and the other strains, while for Verapamil Sprague-Dawley and Wistar-Han showed the lower permeability values. In conclusion, the selection of rat's strain and gender for intestinal absorption experiments is a relevant element during study design and data from different strains may not be always comparable. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. A Review of Food-Drug Interactions on Oral Drug Absorption.

    Science.gov (United States)

    Deng, Jianyuan; Zhu, Xiao; Chen, Zongmeng; Fan, Chun Ho; Kwan, Him Shek; Wong, Chi Ho; Shek, Ka Yi; Zuo, Zhong; Lam, Tai Ning

    2017-11-01

    Food effect, also known as food-drug interactions, is a common phenomenon associated with orally administered medications and can be defined as changes in absorption rate or absorption extent. The mechanisms of food effect and their consequences can involve multiple factors, including human post-prandial physiology, properties of the drug, and how the drug is administered. Therefore, it is essential to have a thorough understanding of these mechanisms when recommending whether a specific drug should be taken with or without food. Food-drug interactions can be clinically relevant, especially when they must be avoided to prevent undesirable effects or exploited to optimize medication therapy. This review conducts a literature search that examined studies on food effect. We summarized the literature and identified and discussed common food effect mechanisms. Furthermore, we highlighted drugs that have a clinically significant food effect and discussed the corresponding mechanisms. In addition, this review analyzes the effects of high-fat food or standard meals on the oral drug absorption rate and absorption extent for 229 drugs based on the Biopharmaceutics Drug Disposition Classification System and demonstrates an association between Biopharmaceutics Drug Disposition Classification System class and food effect.

  8. Semi-solid dosage form of clonazepam for rapid oral mucosal absorption.

    Science.gov (United States)

    Sakata, Osamu; Machida, Yoshiharu; Onishi, Hiraku

    2011-07-01

    In order to obtain an alternative to the intravenous (i.v.) dosage form of clonazepam (CZ), an oral droplet formulation of CZ was developed previously; however, the droplet was physically unstable. Therefore, in the present study, it was attempted to develop an easily-handled dosage form, which was more physically stable and allowed rapid drug absorption from oral mucosa. A semi-solid dosage form, composed of polyethylene glycol 1500 (PEG), CZ, and oleic acid (OA) at 37/1/2 (w/w) and named PEG/CZ/OA, and a semi-solid dosage form containing PEG and CZ at 39/1 (w/w), called PEG/CZ, were prepared. Their physical stability in air at room temperature and oral mucosal absorption in rats were investigated. The semi-solid dosage forms were much more stable physically than the droplet, that is, no recrystallization of CZ was observed for at least 8 days. The effective concentration for humans and rats (20 ng/mL or more) was achieved within 30 min after buccal administration for both PEG/CZ/OA and PEG/CZ. The plasma concentration increased gradually and less varied at each time point for PEG/CZ/OA. PEG/CZ/OA was found to show more rapid and higher absorption of CZ in buccal administration than in sublingual administration. Buccal administration with the semi-solid dosage PEG/CZ with or without OA was suggested to be a possibly useful novel dosage form as an alternative to i.v. injection.

  9. Solid dispersions in oncology: a solution to solubility-limited oral drug absorption

    NARCIS (Netherlands)

    Sawicki, Emilia

    2017-01-01

    This thesis discusses the formulation method solid dispersion and how it works to resolve solubility-limited absorption of orally dosed anticancer drugs. Dissolution in water is essential for drug absorption because only dissolved drug molecules are absorbed. The problem is that half of the arsenal

  10. Food, gastrointestinal pH, and models of oral drug absorption.

    Science.gov (United States)

    Abuhelwa, Ahmad Y; Williams, Desmond B; Upton, Richard N; Foster, David J R

    2017-03-01

    This article reviews the major physiological and physicochemical principles of the effect of food and gastrointestinal (GI) pH on the absorption and bioavailability of oral drugs, and the various absorption models that are used to describe/predict oral drug absorption. The rate and extent of oral drug absorption is determined by a complex interaction between a drug's physicochemical properties, GI physiologic factors, and the nature of the formulation administered. GI pH is an important factor that can markedly affect oral drug absorption and bioavailability as it may have significant influence on drug dissolution & solubility, drug release, drug stability, and intestinal permeability. Different regions of the GI tract have different drug absorptive properties. Thus, the transit time in each GI region and its variability between subjects may contribute to the variability in the rate and/or extent of drug absorption. Food-drug interactions can result in delayed, decreased, increased, and sometimes un-altered drug absorption. Food effects on oral absorption can be achieved by direct and indirect mechanisms. Various models have been proposed to describe oral absorption ranging from empirical models to the more sophisticated "mechanism-based" models. Through understanding of the physicochemical and physiological rate-limiting factors affecting oral absorption, modellers can implement simplified population-based modelling approaches that are less complex than whole-body physiologically-based models but still capture the essential elements in a physiological way and hence will be more suited for population modelling of large clinical data sets. It will also help formulation scientists to better predict formulation performance and to develop formulations that maximize oral bioavailability. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Nasal drug absorption from powder formulations: The effect of three types of hydroxypropyl cellulose (HPC).

    Science.gov (United States)

    Tanaka, Akiko; Furubayashi, Tomoyuki; Tomisaki, Manami; Kawakami, Mayuko; Kimura, Shunsuke; Inoue, Daisuke; Kusamori, Kosuke; Katsumi, Hidemasa; Sakane, Toshiyasu; Yamamoto, Akira

    2017-01-01

    Despite the numerous advantages of powder formulations, few studies have described their nasal drug absorption. The first aim of this study was to compare the drug absorption from powder formulation with that from a liquid formulation in rats. Since pharmaceutical excipients are usually added to most powder formulations, the second aim of the study was to investigate the effect of hydroxypropyl cellulose (HPC) on nasal drug absorption from the powder. Three types of HPC with different polymerization degrees were used: HPC(SL), HPC(M), and HPC(H). The model drugs were warfarin (BCS Class I), piroxicam (BCS Class II), and sumatriptan (BCS Class III). The absorption of these model drugs in the powder form was higher than that from the solution. All HPCs failed to enhance warfarin absorption, while the piroxicam absorption was enhanced only by HPC(M). Sumatriptan absorption was not enhanced by HPC(SL), but by HPC(M) and HPC(H). The differences in nasal absorption of the three model drugs promoted by HPCs depend on the permeability and solubility of the drug. Moreover, the nasal retention of different formulations was increased by HPCs. Because HPCs showed no toxic effect on the nasal epithelium. These findings indicate that powder formulations supplemented with HPC are a valuable and promising approach to increase the nasal absorption of highly soluble and poorly permeable drugs. Copyright © 2016. Published by Elsevier B.V.

  12. A nonlinear numerical model of percutaneous drug absorption.

    Science.gov (United States)

    Kubota, K; Twizell, E H

    1992-03-01

    A nonlinear mathematical model developed by Chandrasekaran et al. is examined to monitor pharmacokinetic profiles in percutaneous drug absorption and is addressed to several associated problems that could occur in the data analysis of in vitro experiments. The formulation of the model gives rise to a nonlinear partial differential equation (PDE) of parabolic type, and a family of finite-difference methods is developed for the numerical solution of the associated initial/boundary-value problem. The value given to a parameter in this family determines the stability properties of the resulting method and whether the solution is obtained explicitly or implicitly. In the case of implicit members of the family it is seen that the solution of the nonlinear PDE is obtained by solving a linear algebraic system, the coefficient matrix of which is tridiagonal. The behaviors of two methods of the family are examined in a series of numerical experiments. Numerical differentiation and integration procedures are combined to monitor the cumulative amount of drug eliminated into the receptor cell per unit area as time increases. It is found that the use of the equation for the simple membrane model to estimate the permeability coefficient and lag time is warranted even if the system should be described by the dual-sorption model, provided cumulative amount versus time data collected for a sufficiently long time are used. However, being different from the behavior in the simple membrane model, the lag time, which can be estimated in this way, is dose-dependent and decreases with increasing donor cell concentration. On the other hand, the permeability coefficient in the dual-sorption model remains constant irrespective of the donor cell concentrations as in the simple membrane model.

  13. [Design and analyze mathematical algorithms of intestinal absorption and metabolism of multicomponent drug].

    Science.gov (United States)

    Dong, Ling; Xiang, Jia-Mei; Wang, Yun; Wu, Rui-Guang; Tang, Ming-Min; Sun, Mo-Han

    2014-12-01

    Evaluation of the permeability mainly focuses on intestinal absorption in biopharmaceutics classification system (BCS). It is more complicated that the absorption and metabolism under multicomponent environment in biopharmaceutics classification system of Chinese materia medica (CMMBCS) compared with single component environment, which needs suitable mathematical models to be described. Therefore, with full consideration of existing single component mathematical algorithm combining with the characteristics of intestinal absorption and metabolism, we explored and designed a new mathematical algorithm of intestinal absorption and metabolism of multicomponent drug. Then we put forward a new coefficient, P (influence), the relative change rate of the single component's intestinal absorption and metabolism under multicomponent environment compared with single component environment, which described the influences of intestinal absorption and metabolism of the component under multicomponent environment. Moreover, P (influence) highlights the distinctive characteristics of multicomponent drug's intestinal absorption and metabolism, and lays the foundation for the construction of CMMBCS.

  14. Application of Physiologically Based Absorption Modeling for Amphetamine Salts Drug Products in Generic Drug Evaluation.

    Science.gov (United States)

    Babiskin, Andrew H; Zhang, Xinyuan

    2015-09-01

    Amphetamine (AMP) salts-based extended-release (ER) drug products are widely used for the treatment of attention deficit hyperactivity disorder. We developed physiologically based absorption models for mixed AMP salts ER capsules and dextroamphetamine sulfate ER capsules to address specific questions raised during generic drug postmarketing surveillance and bioequivalence (BE) guidance development. The models were verified against several data sets. Virtual BE simulations were conducted to assess BE in various populations other than normal healthy subjects where BE studies are generally conducted for approval. The models were also used to predict pharmacokinetics (PK) for hypothetical formulations having dissolution profiles falling within specification after the development of in vitro-in vivo relation. Finally, we demonstrated how to use the models to test sensitivity of PK metrics to the changes in formulation variables. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.

  15. Preclinical dose number and its application in understanding drug absorption risk and formulation design for preclinical species.

    Science.gov (United States)

    Wuelfing, W Peter; Daublain, Pierre; Kesisoglou, Filippos; Templeton, Allen; McGregor, Caroline

    2015-04-06

    In the drug discovery setting, the ability to rapidly identify drug absorption risk in preclinical species at high doses from easily measured physical properties is desired. This is due to the large number of molecules being evaluated and their high attrition rate, which make resource-intensive in vitro and in silico evaluation unattractive. High-dose in vivo data from rat, dog, and monkey are analyzed here, using a preclinical dose number (PDo) concept based on the dose number described by Amidon and other authors (Pharm. Res., 1993, 10, 264-270). PDo, as described in this article, is simply calculated as dose (mg/kg) divided by compound solubility in FaSSIF (mg/mL) and approximates the volume of biorelevant media per kilogram of animal that would be needed to fully dissolve the dose. High PDo values were found to be predictive of difficulty in achieving drug exposure (AUC)-dose proportionality in in vivo studies, as could be expected; however, this work analyzes a large data set (>900 data points) and provides quantitative guidance to identify drug absorption risk in preclinical species based on a single solubility measurement commonly carried out in drug discovery. Above the PDo values defined, >50% of all in vivo studies exhibited poor AUC-dose proportionality in rat, dog, and monkey, and these values can be utilized as general guidelines in discovery and early development to rapidly assess risk of solubility-limited absorption for a given compound. A preclinical dose number generated by biorelevant dilutions of formulated compounds (formulated PDo) was also evaluated and defines solubility targets predictive of suitable AUC-dose proportionality in formulation development efforts. Application of these guidelines can serve to efficiently identify compounds in discovery that are likely to present extreme challenges with respect to solubility-limited absorption in preclinical species as well as reduce the testing of poor formulations in vivo, which is a key

  16. In silico predictions of gastrointestinal drug absorption in pharmaceutical product development: application of the mechanistic absorption model GI-Sim.

    Science.gov (United States)

    Sjögren, Erik; Westergren, Jan; Grant, Iain; Hanisch, Gunilla; Lindfors, Lennart; Lennernäs, Hans; Abrahamsson, Bertil; Tannergren, Christer

    2013-07-16

    Oral drug delivery is the predominant administration route for a major part of the pharmaceutical products used worldwide. Further understanding and improvement of gastrointestinal drug absorption predictions is currently a highly prioritized area of research within the pharmaceutical industry. The fraction absorbed (fabs) of an oral dose after administration of a solid dosage form is a key parameter in the estimation of the in vivo performance of an orally administrated drug formulation. This study discloses an evaluation of the predictive performance of the mechanistic physiologically based absorption model GI-Sim. GI-Sim deploys a compartmental gastrointestinal absorption and transit model as well as algorithms describing permeability, dissolution rate, salt effects, partitioning into micelles, particle and micelle drifting in the aqueous boundary layer, particle growth and amorphous or crystalline precipitation. Twelve APIs with reported or expected absorption limitations in humans, due to permeability, dissolution and/or solubility, were investigated. Predictions of the intestinal absorption for different doses and formulations were performed based on physicochemical and biopharmaceutical properties, such as solubility in buffer and simulated intestinal fluid, molecular weight, pK(a), diffusivity and molecule density, measured or estimated human effective permeability and particle size distribution. The performance of GI-Sim was evaluated by comparing predicted plasma concentration-time profiles along with oral pharmacokinetic parameters originating from clinical studies in healthy individuals. The capability of GI-Sim to correctly predict impact of dose and particle size as well as the in vivo performance of nanoformulations was also investigated. The overall predictive performance of GI-Sim was good as >95% of the predicted pharmacokinetic parameters (C(max) and AUC) were within a 2-fold deviation from the clinical observations and the predicted plasma AUC

  17. Physiologically Based Oral Absorption Modelling to Study Gut-Level Drug Interactions.

    Science.gov (United States)

    Chung, John; Kesisoglou, Filippos

    2017-08-26

    Physiologically based oral absorption models are in silico tools primarily used to guide formulation development and project the clinical performance of formulation variants. This commentary briefly discusses additional oral absorption model applications, focusing on gut-level drug interactions. Gut-level drug interactions can involve drug degradation, metabolic enzymes, transporters, gastrointestinal motility modulators, acid-reducing agents, and food. The growth in publications reporting physiologically based oral absorption model utilization and successful pharmacokinetic prediction (e.g., after acid-reducing agents or food coadministration) indicate that oral absorption models have achieved a level of maturity within the industry particularly over the past 15 years. Provided appropriate data and model validation, oral absorption modeling/simulation may serve as a surrogate for clinical studies by providing both mechanistic and quantitative understanding of oral delivery considerations on pharmacokinetics. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  18. Rapid, Time-Division Multiplexed, Direct Absorption- and Wavelength Modulation-Spectroscopy

    Directory of Open Access Journals (Sweden)

    Alexander Klein

    2014-11-01

    Full Text Available We present a tunable diode laser spectrometer with a novel, rapid time multiplexed direct absorption- and wavelength modulation-spectroscopy operation mode. The new technique allows enhancing the precision and dynamic range of a tunable diode laser absorption spectrometer without sacrificing accuracy. The spectroscopic technique combines the benefits of absolute concentration measurements using calibration-free direct tunable diode laser absorption spectroscopy (dTDLAS with the enhanced noise rejection of wavelength modulation spectroscopy (WMS. In this work we demonstrate for the first time a 125 Hz time division multiplexed (TDM-dTDLAS-WMS spectroscopic scheme by alternating the modulation of a DFB-laser between a triangle-ramp (dTDLAS and an additional 20 kHz sinusoidal modulation (WMS. The absolute concentration measurement via the dTDLAS-technique allows one to simultaneously calibrate the normalized 2f/1f-signal of the WMS-technique. A dTDLAS/WMS-spectrometer at 1.37 µm for H2O detection was built for experimental validation of the multiplexing scheme over a concentration range from 50 to 3000 ppmV (0.1 MPa, 293 K. A precision of 190 ppbV was achieved with an absorption length of 12.7 cm and an averaging time of two seconds. Our results show a five-fold improvement in precision over the entire concentration range and a significantly decreased averaging time of the spectrometer.

  19. Influence of Food on Paediatric Gastrointestinal Drug Absorption Following Oral Administration: A Review

    OpenAIRE

    Batchelor, Hannah K.

    2015-01-01

    The objective of this paper was to review existing information regarding food effects on drug absorption within paediatric populations. Mechanisms that underpin food–drug interactions were examined to consider potential differences between adult and paediatric populations, to provide insights into how this may alter the pharmacokinetic profile in a child. Relevant literature was searched to retrieve information on food–drug interaction studies undertaken on: (i) paediatric oral drug formulat...

  20. Variational finite element method to study the absorption rate of drug ...

    African Journals Online (AJOL)

    Methods: The finite element method has been used to obtain the solution of the mass diffusion equation with appropriate boundary conditions. The tissue absorption rate of drug has been taken as the decreasing function of drug concentration from the skin surface towards the target site. The concentration at nodal points ...

  1. An improved model for studies on transdermal drug absorption in-vivo in rats

    NARCIS (Netherlands)

    Vollmer, U.; Muller, B.W.; Wilffert, B.; Peters, Thies

    1993-01-01

    In rats, transdermal drug absorption can be studied under physiological conditions cannulating the peripheral skin vein, draining the area of the skin which is used for drug application, and collecting the blood. This method leads to decreased blood volume, which causes a reduction in skin blood

  2. THE SLOAN DIGITAL SKY SURVEY REVERBERATION MAPPING PROJECT: RAPID C iv BROAD ABSORPTION LINE VARIABILITY

    Energy Technology Data Exchange (ETDEWEB)

    Grier, C. J.; Brandt, W. N.; Trump, J. R.; Schneider, D. P. [Department of Astronomy and Astrophysics and Institute for Gravitation and the Cosmos, The Pennsylvania State University, 525 Davey Laboratory, University Park, PA 16802 (United States); Hall, P. B. [Department of Physics and Astronomy, York University, Toronto, ON M3J 1P3 (Canada); Shen, Yue [Carnegie Observatories, 813 Santa Barbara Street, Pasadena, CA 91101 (United States); Vivek, M.; Dawson, K. S. [Department of Physics and Astronomy, University of Utah, Salt Lake City, UT 84112 (United States); Ak, N. Filiz [Faculty of Sciences, Department of Astronomy and Space Sciences, Erciyes University, 38039 Kayseri (Turkey); Chen, Yuguang [Department of Astronomy, School of Physics, Peking University, Beijing 100871 (China); Denney, K. D.; Kochanek, C. S.; Peterson, B. M. [Department of Astronomy, The Ohio State University, 140 West 18th Avenue, Columbus, OH 43210 (United States); Green, Paul J. [Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, MA 02138 (United States); Jiang, Linhua [Kavli Institute for Astronomy and Astrophysics, Peking University, Beijing 100871 (China); McGreer, Ian D. [Steward Observatory, The University of Arizona, 933 North Cherry Avenue, Tucson, AZ 85721-0065 (United States); Pâris, I. [INAF-Osservatorio Astronomico di Trieste, Via G. B. Tiepolo 11, I-34131 Trieste (Italy); Tao, Charling [Centre de Physique des Particules de Marseille, Aix-Marseille Universite, CNRS /IN2P3, 163, avenue de Luminy, Case 902, F-13288 Marseille Cedex 09 (France); Wood-Vasey, W. M. [PITT PACC, Department of Physics and Astronomy, University of Pittsburgh, 3941 O’Hara Street, Pittsburgh, PA 15260 (United States); Bizyaev, Dmitry, E-mail: grier@psu.edu [Apache Point Observatory and New Mexico State University, P.O. Box 59, Sunspot, NM, 88349-0059 (United States); and others

    2015-06-10

    We report the discovery of rapid variations of a high-velocity C iv broad absorption line trough in the quasar SDSS J141007.74+541203.3. This object was intensively observed in 2014 as a part of the Sloan Digital Sky Survey Reverberation Mapping Project, during which 32 epochs of spectroscopy were obtained with the Baryon Oscillation Spectroscopic Survey spectrograph. We observe significant (>4σ) variability in the equivalent width (EW) of the broad (∼4000 km s{sup −1} wide) C iv trough on rest-frame timescales as short as 1.20 days (∼29 hr), the shortest broad absorption line variability timescale yet reported. The EW varied by ∼10% on these short timescales, and by about a factor of two over the duration of the campaign. We evaluate several potential causes of the variability, concluding that the most likely cause is a rapid response to changes in the incident ionizing continuum. If the outflow is at a radius where the recombination rate is higher than the ionization rate, the timescale of variability places a lower limit on the density of the absorbing gas of n{sub e} ≳ 3.9 × 10{sup 5} cm{sup −3}. The broad absorption line variability characteristics of this quasar are consistent with those observed in previous studies of quasars, indicating that such short-term variability may in fact be common and thus can be used to learn about outflow characteristics and contributions to quasar/host-galaxy feedback scenarios.

  3. Biopartitioning micellar chromatography: an in vitro technique for predicting human drug absorption.

    Science.gov (United States)

    Molero-Monfort, M; Escuder-Gilabert, L; Villanueva-Camañas, R M; Sagrado, S; Medina-Hernández, M J

    2001-04-05

    The main oral drug absorption barriers are fluid cell membranes and generally drugs are absorbed by a passive diffusion mechanism. Biopartitioning micellar chromatography (BMC) is a mode of micellar liquid chromatography that uses micellar mobile phases of Brij35 under adequate experimental conditions and can be useful to mimic the drug partitioning process in biological systems. In this paper the usefulness of BMC for predicting oral drug absorption in humans is demonstrated. A hyperbolic model has been obtained using the retention data of a heterogeneous set of 74 compounds, which shows predictive ability for drugs absorbed by passive diffusion. The model obtained in BMC is compared with those obtained using the well-known systems (Caco-2 and TC-7) that use intestinal epithelium cell lines. The use of BMC is simple, reproducible and can provide key information about the transport properties of new compounds during the drug discovery process.

  4. Nanostructure of liquid crystalline matrix determines in vitro sustained release and in vivo oral absorption kinetics for hydrophilic model drugs.

    Science.gov (United States)

    Lee, Kathy W Y; Nguyen, Tri-Hung; Hanley, Tracey; Boyd, Ben J

    2009-01-05

    Nanostructured lipid-based liquid crystalline systems have been proposed as sustained oral drug delivery systems, but the interplay between their intrinsic release rates, susceptibility to digestive processes, and the manner in which these effects impact on their application in vivo, are not well understood. In this study, two different bicontinuous cubic phases, prepared from glyceryl monooleate and phytantriol, and a reversed hexagonal phase formed by addition of a small amount of vitamin E to phytantriol (Q(II GMO), Q(II PHYT) and H(II PHYT+VitEA), respectively) were prepared. The release kinetics for a number of model hydrophilic drugs with increasing molecular weights (glucose, Allura Red and FITC-dextrans) was determined in in vitro release experiments. Diffusion-controlled release was observed in all cases as anticipated from previous studies with liquid crystalline systems, and it was discovered that the release rates of each drug decreased as the matrix was changed from Q(II GMO) to Q(II PHYT) to H(II PHYT+VitEA). Formulations containing (14)C-glucose, utilized as a rapidly absorbed marker of drug release, were then orally administered to rats to determine the relative in vivo absorption rates from the different formulations. The results showed a trend by which the rate of absorption of (14)C-glucose followed that observed in the corresponding in vitro release studies, providing the first indication that the nanostructure of these materials may provide the ability to tailor the absorption kinetics of hydrophilic drugs in vivo, and hence form the basis of a new drug delivery system.

  5. Nasal Drug Absorption from Powder Formulations: Effect of Fluid Volume Changes on the Mucosal Surface.

    Science.gov (United States)

    Tanaka, Akiko; Furubayashi, Tomoyuki; Enomura, Yuki; Hori, Tomoki; Shimomura, Rina; Maeda, Chiaki; Kimura, Shunsuke; Inoue, Daisuke; Kusamori, Kosuke; Katsumi, Hidemasa; Sakane, Toshiyasu; Yamamoto, Akira

    2017-01-01

    The effect of changes in the mucosal fluid volume on the nasal drug absorption of powder formulations was evaluated using warfarin (WF), piroxicam (PXC), and norfloxacin (NFX) as model drugs. Lactose and sodium chloride (NaCl), which are water soluble and small-sized chemicals that increase osmotic pressure after dissolution, were used as excipients to change the mucosal fluid volume. The in vitro study using a Madin-Darby canine kidney (MDCK) cell monolayer indicated that lactose and NaCl, sprayed over the surface of air interface monolayers, increased the fluid volume on the monolayer surface and enhanced the transepithelial transport of the model drugs. The in vivo animal study indicated that the nasal absorption of PXC is enhanced by lactose and NaCl after nasal administration of the powder formulations. This is likely due to the enhanced dissolution of PXC on fluid-rich nasal mucosa and an increase in the effective surface area for drug permeation, which lead to better nasal absorption. However, both excipients failed to increase the nasal absorption of WF and NFX. To clarify the mechanism of the drug-dependent effect of lactose and NaCl, the nasal residence of the formulation was examined using FD70 as a non-absorbable marker. The nasal clearance of FD70 was enhanced by lactose and NaCl, leading to a decrease in the nasal drug absorption. Lactose and NaCl caused no damage to the nasal tissue. These results indicate that the addition of water-soluble excipients such as lactose to powder formulations can enhance the nasal absorption of highly permeable but poorly soluble drugs.

  6. Fractional kinetics in drug absorption and disposition processes.

    Science.gov (United States)

    Dokoumetzidis, Aristides; Macheras, Panos

    2009-04-01

    We explore the use of fractional order differential equations for the analysis of datasets of various drug processes that present anomalous kinetics, i.e. kinetics that are non-exponential and are typically described by power-laws. A fractional differential equation corresponds to a differential equation with a derivative of fractional order. The fractional equivalents of the "zero-" and "first-order" processes are derived. The fractional zero-order process is a power-law while the fractional first-order process is a Mittag-Leffler function. The latter behaves as a stretched exponential for early times and as a power-law for later times. Applications of these two basic results for drug dissolution/release and drug disposition are presented. The fractional model of dissolution is fitted successfully to datasets taken from literature of in vivo dissolution curves. Also, the proposed pharmacokinetic model is fitted to a dataset which exhibits power-law terminal phase. The Mittag-Leffler function describes well the data for small and large time scales and presents an advantage over empirical power-laws which go to infinity as time approaches zero. The proposed approach is compared conceptually with fractal kinetics, an alternative approach to describe datasets with non exponential kinetics. Fractional kinetics offers an elegant description of anomalous kinetics, with a valid scientific basis, since it has already been applied in problems of diffusion in other fields, and describes well the data.

  7. Prediction of drug interaction between oral adsorbent AST-120 and concomitant drugs based on the in vitro dissolution and in vivo absorption behavior of the drugs.

    Science.gov (United States)

    Koya, Yohei; Uchida, Shinya; Machi, Yoshiki; Shobu, Yuko; Namiki, Noriyuki; Kotegawa, Tsutomu

    2016-11-01

    AST-120 is used to decrease the abundance of serum uremic toxins in treatment of chronic kidney disease; however, it could also adsorb concomitantly administered drugs. This study aimed to develop a prediction method for drug interaction between AST-120 and concomitantly administered drugs based on in vitro dissolution and in vivo absorption behavior. Sixty-eight drugs were selected for the analysis. For each drug, theoretical dissolution (R d ) and absorption (R a ) rates at estimated dosing intervals (1, 30, 60, 90, 120, and 240 min) were calculated using the Noyes-Whitney formula and compartment analysis, respectively. The optimal thresholds for R d and R a (R dth and R ath ) were estimated by comparing the results with those of previous drug interaction studies for six drugs. Four drug interaction risk categories for 68 drugs at each dose interval were defined according to the indices of dissolution and absorption against their thresholds. The in vitro dissolution and in vivo absorption behavior of the selected drugs were well fitted to the Noyes-Whitney formula and one- or two-compartment models. The optimal R dth and R ath that gave the highest value of consistency with the equivalence of drug interaction studies were 90 and 30 %, respectively. As the dosing intervals were lengthened, the number of drugs classified into the low-risk categories increased. A new drug interaction prediction method based on the pharmacokinetic parameters of drugs was developed. The new model is useful for estimating the risk of drug interaction in clinical practice when AST-120 is used in combination with other drugs.

  8. Rapid diagnosis of tuberculosis. Detection of drug resistance mechanisms.

    Science.gov (United States)

    Viñuelas-Bayón, Jesús; Vitoria, María Asunción; Samper, Sofía

    2017-10-01

    Tuberculosis is still a serious public health problem, with 10.8 million new cases and 1.8 million deaths worldwide in 2015. The diversity among members of the Mycobacterium tuberculosis complex, the causal agent of tuberculosis, is conducive to the design of different methods for rapid diagnosis. Mutations in the genes involved in resistance mechanisms enable the bacteria to elude the treatment. We have reviewed the methods for the rapid diagnosis of M. tuberculosis complex and the detection of susceptibility to drugs, both of which are necessary to prevent the onset of new resistance and to establish early, appropriate treatment. Copyright © 2017 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  9. Rapid interferometric imaging of printed drug laden multilayer structures

    DEFF Research Database (Denmark)

    Sandler, Niklas; Kassamakov, Ivan; Ehlers, Henrik

    2014-01-01

    /and active pharmaceutical ingredients (API) adhere to each other. This is crucial in order to have predetermined drug release profiles. We also demonstrate non-invasive measurement of a polymer structure in a microfluidic channel. It shown that traceable interferometric 3D microscopy is a viable technique......The developments in printing technologies allow fabrication of micron-size nano-layered delivery systems to personal specifications. In this study we fabricated layered polymer structures for drug-delivery into a microfluidic channel and aimed to interferometrically assure their topography...... and adherence to each other. We present a scanning white light interferometer (SWLI) method for quantitative assurance of the topography of the embedded structure. We determined rapidly in non-destructive manner the thickness and roughness of the structures and whether the printed layers containing polymers or...

  10. Predicting Oral Drug Absorption: Mini Review on Physiologically-Based Pharmacokinetic Models

    Directory of Open Access Journals (Sweden)

    Louis Lin

    2017-09-01

    Full Text Available Most marketed drugs are administered orally, despite the complex process of oral absorption that is difficult to predict. Oral bioavailability is dependent on the interplay between many processes that are dependent on both compound and physiological properties. Because of this complexity, computational oral physiologically-based pharmacokinetic (PBPK models have emerged as a tool to integrate these factors in an attempt to mechanistically capture the process of oral absorption. These models use inputs from in vitro assays to predict the pharmacokinetic behavior of drugs in the human body. The most common oral PBPK models are compartmental approaches, in which the gastrointestinal tract is characterized as a series of compartments through which the drug transits. The focus of this review is on the development of oral absorption PBPK models, followed by a brief discussion of the major applications of oral PBPK models in the pharmaceutical industry.

  11. Rapidly dissolving polymeric microneedles for minimally invasive intraocular drug delivery.

    Science.gov (United States)

    Thakur, Raghu Raj Singh; Tekko, Ismaiel A; Al-Shammari, Farhan; Ali, Ahlam A; McCarthy, Helen; Donnelly, Ryan F

    2016-12-01

    In this study, dissolving microneedles (MNs) were used to enhance ocular drug delivery of macromolecules. MNs were fabricated using polyvinylpyrrolidone (PVP) polymer of various molecular weights (MWs) containing three model molecules of increasing MW, namely fluorescein sodium and fluorescein isothiocyanate-dextrans (with MW of 70 k and 150 k Da). Arrays (3 × 3) of PVP MNs with conical shape measuring about 800 μm in height with a 300 μm base diameter, containing the model drugs, were fabricated and characterized for their fracture forces, insertion forces (in the sclera and cornea), depth of penetration (using OCT and confocal imaging), dissolution time and in vitro permeation. The average drug content of the MNs (only in MN shafts) ranged from 0.96 to 9.91 μg, and the average moisture content was below 11 %. High MW PVP produced MNs that can withstand higher forces with minimal reduction in needle height. PVP MNs showed rapid dissolution that ranged from 10 to 180 s, which was dependent upon PVP's MW. In vitro studies showed significant enhancement of macromolecule permeation when MNs were used, across both the corneal and scleral tissues, in comparison to topically applied aqueous solutions. Confocal images showed that the macromolecules formed depots within the tissues, which led to sustained permeation. However, use of MNs did not significantly benefit the permeation of small molecules; nevertheless, MN application has the potential for drug retention within the selected ocular tissues unlike topical application for small molecules. The material used in the fabrication of the MNs was found to be biocompatible with retinal cells (i.e. ARPE-19). Overall, this study reported the design and fabrication of minimally invasive rapidly dissolving polymeric MN arrays which were able to deliver high MW molecules to the eye via the intrastromal or intrascleral route. Thus, dissolving MNs have potential applications in enhancing ocular delivery of both small

  12. Bile salts and their importance for drug absorption

    DEFF Research Database (Denmark)

    Holm, René; Müllertz, Anette; Mu, Huiling

    2013-01-01

    Bile salts are present in the intestines of humans as well as the animals used during the development of pharmaceutical products. This review provides a short introduction into the physical chemical properties of bile salts, a description of the bile concentration and composition of bile...... in different animal species and an overview of the literature investigating the influence of bile salts on the in vivo performance of different compounds and drug formulations. Generally, there is a positive effect on bioavailability when bile is present in the gastro-intestinal tract, independent...

  13. Bile salts and their importance for drug absorption.

    Science.gov (United States)

    Holm, René; Müllertz, Anette; Mu, Huiling

    2013-08-30

    Bile salts are present in the intestines of humans as well as the animals used during the development of pharmaceutical products. This review provides a short introduction into the physical chemical properties of bile salts, a description of the bile concentration and composition of bile in different animal species and an overview of the literature investigating the influence of bile salts on the in vivo performance of different compounds and drug formulations. Generally, there is a positive effect on bioavailability when bile is present in the gastro-intestinal tract, independent of the formulation systems, e.g. suspensions, solutions, cyclodextrin complexes or lipid based formulations, but a few exceptions have also been reported. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. Concomitant intake of alcohol may increase the absorption of poorly soluble drugs.

    Science.gov (United States)

    Fagerberg, Jonas H; Sjögren, Erik; Bergström, Christel A S

    2015-01-25

    Ethanol can increase the solubility of poorly soluble and hence present a higher drug concentration in the gastrointestinal tract. This may produce a faster and more effective absorption resulting in variable and/or high drug plasma concentrations, both of which can lead to adverse drug reactions. In this work we therefore studied the solubility and absorption effects of nine diverse compounds when ethanol was present. The apparent solubility was measured using the μDiss Profiler Plus (pION, MA) in four media representing gastric conditions with and without ethanol. The solubility results were combined with in-house data on solubility in intestinal fluids (with and without ethanol) and pharmacokinetic parameters extracted from the literature and used as input in compartmental absorption simulations using the software GI-Sim. Apparent solubility increased more than 7-fold for non-ionized compounds in simulated gastric fluid containing 20% ethanol. Compounds with weak base functions (cinnarizine, dipyridamole and terfenadine) were completely ionized at the studied gastric pH and their solubility was therefore unaffected by ethanol. Compounds with low solubility in intestinal media and a pronounced solubility increase due to ethanol in the upper gastric compartments showed an increased absorption in the simulations. The rate of absorption of the acidic compounds indomethacin and indoprofen was slightly increased but the extent of absorption was unaffected as the complete doses were readily absorbed even without ethanol. This was likely due to a high apparent solubility in the intestinal compartment where the weak acids are ionized. The absorption of the studied non-ionizable compounds increased when ethanol was present in the gastric and intestinal media. These results indicate that concomitant intake of alcohol may significantly increase the solubility and hence, the plasma concentration for non-ionizable, lipophilic compounds with the potential of adverse drug

  15. Anticancer efficacy and absorption, distribution, metabolism, and toxicity studies of Aspergiolide A in early drug development

    Directory of Open Access Journals (Sweden)

    Wang Y

    2014-10-01

    Full Text Available Yuanyuan Wang, Xin Qi, Dehai Li, Tianjiao Zhu, Xiaomei Mo, Jing LiKey Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao, People's Republic of ChinaAbstract: Since the first anthracycline was discovered, many other related compounds have been studied in order to overcome its defects and improve efficacy. In the present paper, we investigated the anticancer effects of a new anthracycline, aspergiolide A (ASP-A, from a marine-derived fungus in vitro and in vivo, and we evaluated the absorption, distribution, metabolism, and toxicity drug properties in early drug development. We found that ASP-A had activity against topoisomerase II that was comparable to adriamycin. ASP-A decreased the growth of various human cancer cells in vitro and induced apoptosis in BEL-7402 cells via a caspase-dependent pathway. The anticancer efficacy of ASP-A on the growth of hepatocellular carcinoma xenografts was further assessed in vivo. Results showed that, compared with the vehicle group, ASP-A exhibited significant anticancer activity with less loss of body weight. A pharmacokinetics and tissue distribution study revealed that ASP-A was rapidly cleared in a first order reaction kinetics manner, and was enriched in cancer tissue. The maximal tolerable dose (MTD of ASP-A was more than 400 mg/kg, and ASP-A was not considered to be potentially genotoxic or cardiotoxic, as no significant increase of micronucleus rates or inhibition of the hERG channel was seen. Finally, an uptake and transport assay of ASP-A was performed in monolayers of Caco-2 cells, and ASP-A was shown to be absorbed through the active transport pathway. Altogether, these results indicate that ASP-A has anticancer activity targeting topoisomerase II, with a similar structure and mechanism to adriamycin, but with much lower toxicity. Nonetheless, further molecular structure optimization is necessary.Keywords: aspergiolide A, anticancer

  16. Evaluation of skin absorption of drugs from topical and transdermal formulations

    Directory of Open Access Journals (Sweden)

    André Luís Morais Ruela

    Full Text Available ABSTRACT The skin barrier function has been attributed to the stratum corneum and represents a major challenge in clinical practice pertaining to cutaneous administration of drugs. Despite this, a large number of bioactive compounds have been successfully administered via cutaneous administration because of advances in the design of topical and transdermal formulations. In vitro and in vivo evaluations of these novel drug delivery systems are necessary to characterize their quality and efficacy. This review covers the most well-known methods for assessing the cutaneous absorption of drugs as an auxiliary tool for pharmaceutical formulation scientists in the design of drug delivery systems. In vitro methods as skin permeation assays using Franz-type diffusion cells, cutaneous retention and tape-stripping methods to study the cutaneous penetration of drugs, and in vivo evaluations as pre-clinical pharmacokinetic studies in animal models are discussed. Alternative approaches to cutaneous microdialysis are also covered. Recent advances in research on skin absorption of drugs and the effect of skin absorption enhancers, as investigated using confocal laser scanning microscopy, Raman confocal microscopy, and attenuated total reflectance Fourier-transform infrared spectroscopy, are reviewed.

  17. Pre-absorption physicochemical compatibility assessment of 8-drug metabolic cocktail.

    Science.gov (United States)

    Tye, Ching Kim; Wang, Zhanbin; Dockens, Randy C; Vakkalagadda, Blisse; Wang, Chunlei; Zhang, Yingru; Su, Ching Chiang; Hageman, Michael J

    2016-12-05

    A comprehensive 8-drug metabolic cocktail was designed to simultaneously target 6 Cytochrome P450 enzymes and 2 membrane transporters. This study aimed to assess the pre-absorption risk of this new metabolic cocktail which contained metoprolol, caffeine, midazolam, pravastatin, flurbiprofen, omeprazole, digoxin and montelukast. This paper describes a systematic approach to understand whether the co-administration of the 8 selected drug products, i.e., the physical mixing of these products in the human gastro-intestinal environment, will create any issue that may interfere with the individual drug dissolution which in turns modify the total amount or timing of their availability for absorption. The evaluation consisted of two steps. An initial evaluation was based on theoretical understanding of the physicochemical properties of the drugs and the gastro intestinal environment, followed by in vitro dissolution tests. The results indicated that the designer 8-drug cocktail has acceptable pre-absorption compatibility when dosed simultaneously, and recommended the progression of the cocktail into clinical validation study. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Drug-coated microneedles for rapid and painless local anesthesia.

    Science.gov (United States)

    Baek, Sung-Hyun; Shin, Ju-Hyung; Kim, Yeu-Chun

    2017-03-01

    This study showed that drug-coated PLLA (Poly (L-lactide)) microneedle arrays can induce rapid and painless local anesthesia. Microneedle arrays were fabricated using a micro-molding technique, and the needle tips were coated with 290.6 ± 45.9 μg of lidocaine, the most widely used local anesthetic worldwide. A dip-coating device was newly designed for the coating step using an optimized coating formulation. Lidocaine coated on the arrays was released rapidly into PBS within 2 min, and its stability in storage lasted 3 weeks at 4, 25, and 37°C. Furthermore, the microneedle arrays showed consistent in vitro skin penetration and delivered 200.8 ± 43.9, 224.2 ± 39.3, and 244.1 ± 19.6 μg of lidocaine into the skin 1, 2, and 5 min after application with a high delivery efficiency of 69, 77, and 84%. Compared to a commercially available topical anesthetic EMLA® cream, a 22.0, 13.6, and 14.0-fold higher amount of lidocaine was delivered into the skin. Note, in vitro skin permeation of Lidocaine was also notably enhanced by a 2-min-application of the lidocaine-coated microneedle arrays. Altogether, these results suggest that the biocompatible lidocaine-coated PLLA microneedle arrays could provide significantly rapid local anesthesia in a painless manner without any of the issues from topical applications or hypodermic injections of local anesthetics.

  19. Erythrocyte adenosine transport. A rapid screening test for cardiovascular drugs.

    Science.gov (United States)

    Yeung, P K; Mosher, S J; Li, R; Farmer, P S; Klassen, G A; Pollak, P T; McMullen, M; Ferrier, G

    1993-11-01

    An erythrocyte (RBC) model based on whole blood was used to investigate the effect of cardiovascular drugs on the uptake of adenosine in vitro. Fresh whole blood obtained from healthy volunteers was allowed to equilibrate with various concentrations (5-1000 microM) of a tested agent. (2-3H)-Adenosine was used as a substrate, and the reaction was terminated after 2 sec of incubation at room temperature by rapid addition of a "Stopping Solution" which was a mixture of erythro-9-(2-hydroxy-3-nonyl)adenine, dipyridamole, and EDTA. The mixture was centrifuged (1760 g, 4 degrees C, 10 min), and the radioactivity of an aliquot of the supernatant was determined by a scintillation counter. The results showed that dipyridamole was the most potent agent tested (IC50 = 0.2 microM). Amongst the calcium antagonists studied, isradipine was most potent, followed by verapamil, clentiazem, diltiazem, and then nifedipine. The racemates of two metabolites of diltiazem, MX and MB, were more potent than the parent drug. The antiarrhythmic agents, amiodarone and sotalol, the two new lipid peroxidation inhibitors, U-74389F and U-78517F, and the anxiolytic agent, alprazolam, were as active as verapamil. The beta-receptor antagonist propranolol and the angiotensin converting enzyme (ACE) inhibitor, enalapril, were practically inactive. In addition, the model was stereoselective such that the S(-)-enantiomer of verapamil was considerably more potent than the R(+)-antipote, whereas d(+)-sotalol was practically inactive compared to racemic sotalol.

  20. MOSFIRE ABSORPTION LINE SPECTROSCOPY OF z > 2 QUIESCENT GALAXIES: PROBING A PERIOD OF RAPID SIZE GROWTH

    Energy Technology Data Exchange (ETDEWEB)

    Belli, Sirio; Ellis, Richard S.; Konidaris, Nick P. [Department of Astronomy, California Institute of Technology, MS 249-17, Pasadena, CA 91125 (United States); Newman, Andrew B. [The Observatories of the Carnegie Institution for Science, 813 Santa Barbara Street, Pasadena, CA 91101 (United States)

    2014-06-20

    Using the MOSFIRE near-infrared multi-slit spectrograph on the Keck 1 Telescope, we have secured high signal-to-noise ratio absorption line spectra for six massive galaxies with redshift 2 < z < 2.5. Five of these galaxies lie on the red sequence and show signatures of passive stellar populations in their rest-frame optical spectra. By fitting broadened spectral templates we have determined stellar velocity dispersions and, with broad-band Hubble Space Telescope and Spitzer photometry and imaging, stellar masses and effective radii. Using this enlarged sample of galaxies, we confirm earlier suggestions that quiescent galaxies at z > 2 have small sizes and large velocity dispersions compared to local galaxies of similar stellar mass. The dynamical masses are in very good agreement with stellar masses (log M {sub *}/M {sub dyn} = –0.02 ± 0.03), although the average stellar-to-dynamical mass ratio is larger than that found at lower redshift (–0.23 ± 0.05). By assuming evolution at fixed velocity dispersion, not only do we confirm a surprisingly rapid rate of size growth but we also consider the necessary evolutionary track on the mass-size plane and find a slope α = dlog R{sub e} /dlog M {sub *} ≳ 2 inconsistent with most numerical simulations of minor mergers. Both results suggest an additional mechanism may be required to explain the size growth of early galaxies.

  1. Mechanisms of membrane transport of poorly soluble drugs: role of micelles in oral absorption processes.

    Science.gov (United States)

    Yano, Koji; Masaoka, Yoshie; Kataoka, Makoto; Sakuma, Shinji; Yamashita, Shinji

    2010-03-01

    Micelles formed in the GI tract by bile acid and lecithin play an important role in oral absorption of poorly soluble drugs. In this situation, the drug molecules are present in equilibrium between the free and micellar states. In this study, the relationship between the free drug concentration and the membrane permeability of poorly soluble drugs was examined. Permeability across a Caco-2 monolayer and a dialysis membrane were measured in a side-by-side chamber system. The concentrations of sodium taurocholate (NaTC) and lecithin were varied to allow measurement of membrane permeability at different concentrations of free drugs. For troglitazone, hexylparaben, and heptylparaben, an increase in the NaTC and lecithin concentrations caused the permeability across the Caco-2 monolayer to decrease slightly, whereas the permeability across the dialysis membrane decreased markedly. In contrast, the changes in permeability of griseofulvin with an increased micelle concentration were similar for the Caco-2 monolayer and the dialysis membrane. Assuming that the permeability for the dialysis membrane reflects the free drug concentration in the medium, these results suggest that troglitazone and alkylparabens, but not griseofulvin, can partition directly from micelles to Caco-2 monolayers. This mechanism may contribute to oral absorption of drugs that are poorly soluble in water. 2009 Wiley-Liss, Inc. and the American Pharmacists Association

  2. Application of Absorption Modeling in Rational Design of Drug Product Under Quality-by-Design Paradigm.

    Science.gov (United States)

    Kesisoglou, Filippos; Mitra, Amitava

    2015-09-01

    Physiologically based absorption models can be an important tool in understanding product performance and hence implementation of Quality by Design (QbD) in drug product development. In this report, we show several case studies to demonstrate the potential application of absorption modeling in rational design of drug product under the QbD paradigm. The examples include application of absorption modeling—(1) prior to first-in-human studies to guide development of a formulation with minimal sensitivity to higher gastric pH and hence reduced interaction when co-administered with PPIs and/or H2RAs, (2) design of a controlled release formulation with optimal release rate to meet trough plasma concentrations and enable QD dosing, (3) understanding the impact of API particle size distribution on tablet bioavailability and guide formulation design in late-stage development, (4) assess impact of API phase change on product performance to guide specification setting, and (5) investigate the effect of dissolution rate changes on formulation bioperformance and enable appropriate specification setting. These case studies are meant to highlight the utility of physiologically based absorption modeling in gaining a thorough understanding of the product performance and the critical factors impacting performance to drive design of a robust drug product that would deliver the optimal benefit to the patients.

  3. Drug marker absorption in relation to pellet size, gastric motility and viscous meals in humans

    Science.gov (United States)

    Rhie, J. K.; Hayashi, Y.; Welage, L. S.; Frens, J.; Wald, R. J.; Barnett, J. L.; Amidon, G. E.; Putcha, L.; Amidon, G. L.

    1998-01-01

    PURPOSE: The objective of this study was to evaluate drug marker absorption in relation to the gastric emptying (GE) of 0.7 mm and 3.6 mm enteric coated pellets as a function of viscosity and the underlying gastric motility. METHODS: Twelve subjects were evaluated in a 3-way crossover study. 0.7 mm caffeine and 3.6 mm acetaminophen enteric coated pellets were concurrently administered with a viscous caloric meal at the levels of 4000, 6000 and 8000 cP. Gastric motility was simultaneously measured with antral manometry and compared to time events in the plasma profiles of the drug markers. RESULTS: Caffeine, from the 0.7 mm pellets, was observed significantly earlier in the plasma than acetaminophen, from the 3.6 mm pellets, at all levels of viscosity. Motility related size differentiated GE was consistently observed at all viscosity levels, however, less variability was observed with the 4000 cP meal. Specifically, the onset of absorption from the of 3.6 mm pellets correlated with the onset of Phase II fasted state contractions (r = 0.929, p < 0.01). CONCLUSIONS: The timeframe of drug marker absorption and the onset of motility events were not altered within the range of viscosities evaluated. Rather, the differences in drug marker profiles from the non-digestible solids were most likely the result of the interaction between viscosity and motility influencing antral flow dynamics. The administration of the two sizes of pellets and a viscous caloric meal with subsequent monitoring of drug marker profiles is useful as a reference to assess the influence of motility patterns on the absorption profile of orally administered agents.

  4. Efficacy, safety and mechanism of HP-β-CD-PEI polymers as absorption enhancers on the intestinal absorption of poorly absorbable drugs in rats.

    Science.gov (United States)

    Zhang, Hailong; Huang, Xiaoyan; Zhang, Yongjing; Gao, Yang

    2017-03-01

    Oral bioavailability of some hydrophilic therapeutic macromolecules was very poor, thus leading to their limited application in clinic. To investigate the efficacy, safety and mechanism of HP-β-CD-PEI polymers on the intestinal absorption of some poorly absorbable drugs in rats. Effects of HP-β-CD-PEI polymers on the intestinal absorptions of drugs were investigated by an in situ closed loop method in rats. The safety of HP-β-CD-PEI polymer was evaluated by measurement of lactate dehydrogenase (LDH) activity and amount of protein released from rat intestinal perfusate. The absorption enhancing mechanisms were explored by the measurement of zeta potential, transepithelial electrical resistance (TEER) and in vitro transport of FD4 (a paracellular marker) across rat intestinal membranes, respectively. HP-β-CD-PEI polymers, especially HP-β-CD-PEI1800, demonstrated excellent absorption enhancing effects on drug absorption in a concentration-dependent manner and the enhancing effect was more efficient in the small intestine than that in the large intestine. Five percent (w/v) HP-β-CD-PEI1800 obviously decreased the TEER, accompanied with increase in the intestinal transport of FD4, indicating that absorption enhancing actions of HP-β-CD-PEI polymers were possibly performed by loosening tight junctions of intestinal epithelium cells, thereby increasing drug permeation via a paracellular pathway. A good liner relationship between absorption enhancing effects of HP-β-CD-PEI polymers and their zeta potentials suggested the contribution of positive charge on the surface of these polymers to their absorption enhancing effects. HP-β-CD-PEI polymers might be potential and safe absorption enhancers for improving oral delivery of poorly absorbable macromolecules including peptides and proteins.

  5. Noninvasive monitoring of glucose concentration using differential absorption low-coherence interferometry based on rapid scanning optical delay line

    Energy Technology Data Exchange (ETDEWEB)

    Zhou Yong; Zeng Nan; He Yonghong, E-mail: heyh@sz.tsinghua.edu.cn [Laboratory of Optical Imaging and Sensing, Graduate School at Shenzhen, Tsinghua University, Shenzhen, 518055 (China)

    2011-01-01

    A non-invasive method of detecting glucose concentration using differential absorption low-coherence interferometry (DALCI) based on rapid scanning optical delay line is presented. Two light sources, one centered within (1625 nm) a glucose absorption band, while the other outside (1310 nm) the glucose absorption band, are used in the experiment. The low-coherence interferometry (LCI) is employed to obtain the signals back-reflecting from the iris which carries the messages of material concentration in anterior chamber. Using rapid scanning optical delay line (RSOD) as the reference arm, we can detect the signals in a very short time. Therefore the glucose concentration can be monitored in real-time, which is very important for the detection in vivo. In our experiments, the cornea and aqueous humor can be treated as nearly non-scattering substance. The difference in the absorption coefficient is much larger than the difference in the scattering coefficient, so the influence of scattering can be neglected. By subtracting the algorithmic low-coherence interference signals of the two wavelengths, the absorption coefficient can be calculated which is proportional to glucose concentration. To reduce the speckle noise, a 30 variation of signals were used before the final calculation of the glucose concentration. The improvements of our experiment are also discussed in the article. The method has a potential application for noninvasive detection of glucose concentration in vivo and in real-time.

  6. Relationship between lipophilicity of BCS class III and IV drugs and the functional activity of peroral absorption enhancers.

    Science.gov (United States)

    Sharma, Pradeep; Varma, Manthena V S; Chawla, Harmander P S; Panchagnula, Ramesh

    2005-01-01

    Absorption enhancers (AEs) have been shown to be specific in permeation enhancement capabilities because of which they increase absorption of some drug molecules more than others. Present study was designed to investigate the relationship between lipophilicity of drug molecules and the absorption enhancement potential of AEs. Four drug molecules of different lipophilicity were selected as model compounds, namely, cefotaxime sodium, ceftazidime pentahydrate, lovastatin and cyclosporin A. Their apparent permeability coefficients in the absence and presence of three classes of AEs (fatty acids, cyclodextrins, and bile salts) were determined using in vitro everted rat intestinal sac absorption model. Significant relationship was observed between log P of drug and absorption enhancement ratios by AEs. This relationship was found to be functionally directly or indirectly proportional depending upon nature of AE and explain the mechanism of permeation enhancement.

  7. Enhancement of oral absorption of curcumin by self-microemulsifying drug delivery systems.

    Science.gov (United States)

    Cui, Jing; Yu, Bo; Zhao, Yu; Zhu, Weiwei; Li, Houli; Lou, Hongxiang; Zhai, Guangxi

    2009-04-17

    Curcumin is a poorly water-soluble drug and its oral bioavailability is very low. A new self-microemulsifying drug delivery system (SMEDDS) has been successfully developed to improve the solubility and oral absorption of curcumin. Suitable compositions of SMEDDS formulation were screened via solubility studies of curcumin and compatibility tests. The formulation of curcumin-loaded SMEDDS was optimized by a simplex lattice experiment design. The optimal formulation of SMEDDS was comprised of 57.5% surfactant (emulsifier OP:Cremorphor EL = 1:1), 30.0% co-surfactant (PEG 400) and 12.5% oil (ethyl oleate). The solubility of curcumin (21 mg/g) significantly increased in SMEDDS. The average particle size of SMEDDS-containing curcumin was about 21 nm when diluted in water. No significant variations in particle size and curcumin content in SMEDDS were observed over a period of 3 months at 4 degrees C. The spherical shape of microemulsion droplet was observed under TEM. The dissolution study in vitro showed that more than 95% of curcumin in SMEDDS could be dissolved in pH 1.2 or pH 6.8 buffer solutions in 20 min, however, less than 2% for crude curcumin in 60 min.The in situ absorption property of curcumin-loaded SMEDDS was evaluated in intestines of rats. The results showed the absorption of curcumin in SMEDDS was via passive transfer by diffusion across the lipid membranes. The results of oral absorption experiment in mice showed that SMEDDS could significantly increase the oral absorption of curcumin compared with its suspension. Our study illustrated that the developed SMEDDS formulation held great potential as a possible alternative to traditional oral formulations of curcumin.

  8. Effect of aminoalkyl methacrylate copolymer E/HCl on in vivo absorption of poorly water-soluble drug.

    Science.gov (United States)

    Yoshida, Takatsune; Kurimoto, Ippei; Yoshihara, Keiichi; Umejima, Hiroyuki; Ito, Naoki; Watanabe, Shunsuke; Sako, Kazuhiro; Kikuchi, Akihiko

    2013-11-01

    This study aimed to investigate in vivo absorption of tacrolimus formulated as a solid dispersion using Eudragit E®/HCl (E-SD). E-SD is an aminoalkyl methacrylate copolymer that can be dissolved under neutral pH conditions. E-SD was used alone as a solid dispersion carrier and/or was mixed with tacrolimus primarily dispersed with hydroxypropylmethylcellulose (HPMC). Tacrolimus was formulated with E-SD at several different ratios. Formulations with tacrolimus/E-SD ratio of 1/3 showed higher in vivo absorption, compared to tacrolimus dispersed in the excipients (primarily HPMC) found in commercially available tacrolimus capsules, using a rat in situ closed loop method. Good correlation was observed between in vitro drug solubility and in vivo drug absorption. In vitro solubility tests and rat oral absorption studies of tacrolimus/HPMC solid dispersion formulations were also conducted after mixing the HPMC dispersion with several ratios of E-SD. E-SD/tacrolimus/HPMC formulations yielded high in vitro drug solubility but comparatively low in vivo absorption. Dog oral absorption studies were conducted using capsules containing a formulation of tacrolimus/E-SD at a ratio of 1/5. The E-SD formulation-containing capsule showed higher in vivo drug absorption than tacrolimus dispersed in the standard HPMC capsule. These studies report enhancement of the in vivo absorption of a poorly water-soluble drug following dispersion with E-SD when compared to formulation in HPMC.

  9. Two-photon absorption-induced drug delivery from polymers for medical applications

    Science.gov (United States)

    Kim, Hee-Cheol; Kreiling, Stefan; Haertner, Sebastian; Hesse, Lutz; Greiner, Andreas; Hampp, Norbert A.

    2004-06-01

    Novel polymeric materials carrying a drug depot have been developed which are suitable for fabrication of photochemically modulated drug delivery devices. In order to avoid uncontrolled drug release the drug is covalently attached to the polymer backbone using a photo-active linker. Controlled drug release from the polymer can be accomplished either via single-photon excitation or by two-photon absorption (TPA). In particular the second possibility is of interest for applications where exposure to day light or UV light may not be omitted. One example are polymeric intraocular lenses (IOL), which are implanted instead of the opaque natural lens during cataract surgery. Secondary cataract formation is quite often observed after implantation of polymeric IOLs. In this study the well known cell toxic agent 5-fluorouracil (5FU) attached to a methylmethacrylate-based polymer was investigated as an IOL which can upon photochemical excitation release 5FU in order to treat or to prevent secondary cataract formation. The photochemical cleavage of the linker molecule was analyzed with single- and two-photon excitation. UV/VIS spectroscopy and HPLC analysis confirmed the release of 5FU form the polymer backbone. The diffusion of the drug precursor out from the polymer as well as the hydrolysis of the drug precursor which leads to 5FU formation were investigated in vitro.

  10. Time Domain Technique for Rapid, Broadband Measurement of Human Absorption Cross Section in a Reverberation Chamber

    OpenAIRE

    Robinson, Martin P; Zhang, Xiaotian; Flintoft, Ian D.

    2017-01-01

    Absorption cross section (ACS) of an object is used in stochastic power balance models, while human ACS is closely related to microwave dosimetry parameters such as specific absorption rate (SAR) and thus characterises exposure as well as effect of human bodies on multipath propagation. ACS, averaged over all directions of incidence, can be obtained in the frequency domain from the S-parameters of two antennas in a stirred-mode reverberation chamber; however, our new time domain method is fas...

  11. An introduction to drug disposition: the basic principles of absorption, distribution, metabolism, and excretion.

    Science.gov (United States)

    Caldwell, J; Gardner, I; Swales, N

    1995-01-01

    A knowledge of the fate of a drug, its disposition (absorption, distribution, metabolism, and excretion, known by the acronym ADME) and pharmacokinetics (the mathematical description of the rates of these processes and of concentration-time relationships), plays a central role throughout pharmaceutical research and development. These studies aid in the discovery and selection of new chemical entities, support safety assessment, and are critical in defining conditions for safe and effective use in patients. ADME studies provide the only basis for critical judgments from situations where the behavior of the drug is understood to those where it is unknown: this is most important in bridging from animal studies to the human situation. This presentation is intended to provide an introductory overview of the life cycle of a drug in the animal body and indicates the significance of such information for a full understanding of mechanisms of action and toxicity.

  12. Influence of Food on Paediatric Gastrointestinal Drug Absorption Following Oral Administration: A Review.

    Science.gov (United States)

    Batchelor, Hannah K

    2015-06-09

    The objective of this paper was to review existing information regarding food effects on drug absorption within paediatric populations. Mechanisms that underpin food-drug interactions were examined to consider potential differences between adult and paediatric populations, to provide insights into how this may alter the pharmacokinetic profile in a child. Relevant literature was searched to retrieve information on food-drug interaction studies undertaken on: (i) paediatric oral drug formulations; and (ii) within paediatric populations. The applicability of existing methodology to predict food effects in adult populations was evaluated with respect to paediatric populations where clinical data was available. Several differences in physiology, anatomy and the composition of food consumed within a paediatric population are likely to lead to food-drug interactions that cannot be predicted based on adult studies. Existing methods to predict food effects cannot be directly extrapolated to allow predictions within paediatric populations. Development of systematic methods and guidelines is needed to address the general lack of information on examining food-drug interactions within paediatric populations.

  13. Rapid Methods for detection of Veterinary Drug residues in Meat

    Directory of Open Access Journals (Sweden)

    Chandan

    2010-10-01

    Full Text Available The use of substances having hormonal or thyreostatic action as well as b-agonists is banned in many countries. However, sometimes forbidden drugs may be added to feeds for illegal administration to farm animals for promoting increased muscle development or increased water retention and thus obtain an economical benefit. The result is a fraudulent overweight of meat but, what is worse, residues of these substances may remain in meat and may pose a real threat to the consumer either through exposure to the residues, transfer of antibiotic resistance or allergy risk. This has exerted a great concern among the meat consumers. The control of the absence of these forbidden substances in animal foods and feeds is regulated in the European Union by Directive 96/23/EC on measures to monitor certain substances and residues in live animals and animal products. Analytical methodology, including criteria for identification and confirmation, for the monitoring of compliance was also given in Decisions 93/256/EEC and 93/257/EEC. More recently, Decision 2002/657/EC provided rules for the analytical methods to be used in testing of official samples. New substances with anabolic properties are being detected year by year increasing the list of forbidden compounds to be tested. Furthermore, the extended practice consisting in the use of “cocktails” (mixtures of low amounts of several substances that exert a synergistic effect to have a similar growth promotion, reduces the margin for an effective analytical detection. Thus, the evolution of the “black market” is making really difficult to have an effective analytical control of the residues of these substances in foods of animal origin. Control laboratories must face an increasing demand of analysis like the growing number of residues to be analysed in different types of samples, the strict guidelines for analytical methodologies according to the latest Directives, the increased costs of such new

  14. Advantage of the Dissolution/Permeation System for Estimating Oral Absorption of Drug Candidates in the Drug Discovery Stage.

    Science.gov (United States)

    Miyaji, Yoshihiro; Fujii, Yoshimine; Takeyama, Shoko; Kawai, Yukinori; Kataoka, Makoto; Takahashi, Masayuki; Yamashita, Shinji

    2016-05-02

    In order to increase the success rate in the development of oral drugs, an in vitro method, which can accurately estimate human oral absorption of a large variety of compounds from solid formulations, is required in the drug discovery stage. A dissolution/permeation (D/P) system is an in vitro system that simultaneously evaluates dissolution and permeation processes of drugs administered orally. In this study, we have investigated the advantages of a D/P system for use in the provisional estimation of human oral absorption of a drug (absorbed fraction, Fa) by applying it in its solid state. The D/P system mounted with a Madin-Darby canine kidney (MDCK) II cell monolayer was used to simultaneously evaluate the dissolved and the permeated amounts (% of dose) of 48 marketed drugs. Slightly modified, fasted-state simulated intestinal fluid (FaSSIFmod, 8 mL) was used as the apical medium of the D/P system. Each test drug was applied to the apical side of the D/P system as a suspension at one-hundredth of the clinical dose. The apparent permeability coefficient across the MDCK II cell monolayer was estimated in a buffer solution (pH 6.5). The octanol/water distribution coefficient (Log D) was measured at pH 6.5 by a flask shaking method. Transport medium (TM, pH 6.5), a buffer solution removing lecithin and taurocholate from FaSSIFmod, was used to determine the solubility at 24 h after applying drugs. The solubility in TM was used as a free drug concentration in FaSSIFmod. A good correlation was obtained between observed human Fa and the permeated amount in the D/P system. When the sigmoidal curve was obtained by the curve fitting to the data, the determination coefficient was R(2) = 0.79 and the 95% interval of the predicted Fa values was about ±24% for all drugs tested in the present study. For comparison, the permeated amount was calculated by multiplying the permeability of each drug (in vitro Papp) by the solubility in FaSSIFmod. However, the calculated permeated

  15. Amorphous Solid Dispersions or Prodrugs: Complementary Strategies to Increase Drug Absorption.

    Science.gov (United States)

    Rumondor, Alfred C F; Dhareshwar, Sundeep S; Kesisoglou, Filippos

    2016-09-01

    Maximizing oral bioavailability of drug candidates represents a challenge in the pharmaceutical industry. In recent years, there has been an increase in the use of amorphous solid dispersions (ASDs) to address this issue, where a growing number of solid dispersion formulations have been introduced to the market. However, an increase in solubility or dissolution rate through ASD does not always result in sufficient improvement of oral absorption because solubility limitations may still exist at high doses. Chemical modification in the form of a prodrug may offer an alternative approach for these cases. Although prodrugs have been primarily used to improve membrane permeability, examples are available in which prodrugs have been used to increase drug solubility beyond what can be achieved via formulation approaches. In this mini review, the role of ASDs and prodrugs as 2 complementary approaches in improving oral bioavailability of drug candidates is discussed. We discuss the fundamental principles of absorption and bioavailability, and review available literature on both solid dispersions and prodrugs, providing a summary of their use and examples of successful applications, and cover some of the biopharmaceutics evaluation aspects for these approaches. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  16. Imaging Laser-Triggered Drug Release from Gold Nanocages with Transient Absorption Lifetime Microscopy.

    Science.gov (United States)

    Xu, Yongkui; Liu, Qi; He, Ruoyu; Miao, Xianchong; Ji, Minbiao

    2017-06-14

    Nanoparticles have shown promise in loading and delivering drugs for targeted therapy. Many progresses have been made in the design, synthesis, and modification of nanoparticles to fulfill such goals. However, realizing targeted intracellular delivery and controlled release of drugs remains challenging, partly because of the lack of reliable tools to detect the drug-releasing process. In this paper, we applied femtosecond laser pulses to trigger the explosion of gold nanocages (AuNCs) and control the intracellular release of loaded aluminum phthalocyanine (AlPcS) molecules for photodynamic therapy (PDT). AuNCs were found to enhance the encapsulation efficiency and suppress the PDT effect of AlPcS molecules until they were released. More importantly, we discovered that the excited-state lifetimes of the AlPcS-AuNC conjugate (∼3 ps) and free AlPcS (∼11 ps) differ significantly, which was utilized to image the released drug molecules using transient absorption lifetime microscopy with the same laser source. This technique extracts information similar to fluorescence lifetime imaging microscopy but is superior in imaging the molecules that hardly fluoresce or are prone to photobleaching. We further combined a dual-phase lock-in detection technique to show the potential of real-time imaging based on the change in transient optical behaviors. Our method may provide a new tool for investigating nanoparticle-assisted drug delivery and release.

  17. Influence of pH on Drug Absorption from the Gastrointestinal Tract: A Simple Chemical Model

    Science.gov (United States)

    Hickman, Raymond J. S.; Neill, Jane

    1997-07-01

    A simple model of the gastrointestinal tract is obtained by placing ethyl acetate in contact with water at pH 2 and pH 8 in separate test tubes. The ethyl acetate corresponds to the lipid material lining the tract while the water corresponds to the aqueous contents of the stomach (pH 2) and intestine (pH 8). The compounds aspirin, paracetamol and 3-aminophenol are used as exemplars of acidic, neutral and basic drugs respectively to illustrate the influence which pH has on the distribution of each class of drug between the aqueous and organic phases of the model. The relative concentration of drug in the ethyl acetate is judged by applying microlitre-sized samples of ethyl acetate to a layer of fluorescent silica which, after evaporation of the ethyl acetate, is viewed under an ultraviolet lamp. Each of the three drugs, if present in the ethyl acetate, becomes visible as a dark spot on the silica layer. The observations made in the model system correspond well to the patterns of drug absorption from the gastrointestinal tract described in pharmacology texts and these observations are convincingly explained in terms of simple acid-base chemistry.

  18. Determination of toxic metals in some herbal drugs through atomic absorption spectroscopy.

    Science.gov (United States)

    Hina, Bushra; Rizwani, Ghazala Hafeez; Naseem, Shahid

    2011-07-01

    This study presents a picture of occurrence of heavy metals (Pb, Cd, Cu, Cr, Co, Fe, Ni, Zn) in some selected valuable herbal drugs (G. glabra, O. bracteatum, V. odorata , F. vulgare, C. cyminum, C. sativum, and Z. officinalis) purchased from three different zones (southern, eastern, and western) of Karachi city using atomic absorption spectrophotometer. Heavy metal concentrations in these drugs were found in the range of: 3.26-30.46 for Pb, 1.6-4.91 for Cd, 0.65-120.21 for Cu, 83.74-433.76 for Zn, 1.61-186.75 for Cr, 0.48-76.97 for Ni, 5.54-77.97 for Co and 65.68-1652.89 µg/g for Fe. Percentage of heavy metals that were found beyond the permissible limits were: 71.4% for Pb, 28.51% for Cd, 14.2% for Cu, and 9.5 % for Cr. Significant difference was noticed for each heavy metal among herbal drugs as well as their zones of collection using two way ANOVA followed by least significant (LSD) test at p<0.05.Purpose of this research is to detect each type of heavy metal contaminant of herbal drugs by environmental pollution, as well as to highlight the health risks associated with the use of such herbal drugs that contain high levels of toxic heavy metals.

  19. Cost-effectiveness of rapid susceptibility testing against second-line drugs for tuberculosis

    NARCIS (Netherlands)

    Dowdy, D. W.; van't Hoog, A.; Shah, M.; Cobelens, F.

    2014-01-01

    Drug susceptibility testing (DST) against second-line tuberculosis drugs (SLDs) is essential for improving outcomes among multidrug-resistant (MDR-) and extensively drug-resistant tuberculosis (XDR-TB) cases. To evaluate the potential cost-effectiveness of rapid DST for SLDs. We constructed a

  20. Rapid accurate analysis of metal (oxide)-on-silica catalysts by atomic absorption spectrometry

    NARCIS (Netherlands)

    Jütte, B.A.H.G.; Heikamp, A.; Agterdenbos, J.

    1979-01-01

    The catalysts, which contain 10–60% copper, chromium, nickel and silicon, are decomposed in sealed Teflon-lined vessels and analyzed by atomic absorption spectrometry. Matrix matching and bracketing standards are applied. The RSD of a single determination is about 1% for all components.

  1. The Effect of Digestion and Drug Load on Halofantrine Absorption from Self-nanoemulsifying Drug Delivery System (SNEDDS)

    DEFF Research Database (Denmark)

    Michaelsen, Maria Hotoft; Wasan, Kishor M.; Sivak, Olena

    2016-01-01

    A super-saturated self-nanoemulsifying drug delivery system (super-SNEDDS), containing the poorly water-soluble drug halofantrine (Hf) at 150% of equilibrium solubility (Seq), was compared in vitro and in vivo with a conventional SNEDDS (75% of Seq) with respect to bioavailability and digestibility....... Further, the effect of digestion on oral absorption of Hf from SNEDDS and super-SNEDDS was assessed by incorporation of the lipase inhibitor tetrahydrolipstatin (orlistat) into the SNEDDS. The SNEDDS contained soybean oil/Maisine 34-I (1:1), Kolliphor RH40, and ethanol at a ratio of 55:35:10, w/w percent....... For the dynamic in vitro lipolysis, the precipitation of Hf at 60 min was significantly larger for the super-SNEDDS (66.8 ± 16.4%) than for the SNEDDS (18.5 ± 9.2%). The inhibition of the in vitro digestion by orlistat (1% (w/w)) lowered drug precipitation significantly for both the super-SNEDDS (36.8 ± 1...

  2. The effects of black pepper on the intestinal absorption and hepatic metabolism of drugs.

    Science.gov (United States)

    Han, Hyo-Kyung

    2011-06-01

    There is currently a need for a better understanding of the mechanisms of food-drug interaction as well as the clinical implication to maximize the effectiveness and applicability of black pepper or its active component, piperine, as a bioavailability enhancer in the clinical arena. This review deals with the effects of black pepper and piperine on drug metabolizing enzymes as well as on intestinal drug absorption. The review provides the reader with a comprehensive update on the potential mechanisms and pharmacokinetic interactions of black pepper and piperine with co-administered medicines. The article also provides a comprehensive update on the current known issues with black pepper and piperine. The information provided is used to assess the clinical significance of black pepper and piperine and optimize their effectiveness as a bioavailability enhancer. For black pepper or piperine to be widely applicable in current medical practice, as a combination therapy, the clinical significance of food-drug interactions caused by concurrent use of black pepper or piperine should be carefully assessed with consideration for many compounding factors affecting the clinical outcome of pharmacokinetic interactions (e.g., dose, dosing regimen, genetic variation and species). Furthermore, the effective formulation strategy for the optimization of the pharmacokinetic characteristics of dietary components is crucial to improve their in vivo performance and ultimately maximize their effectiveness as a bioavailability enhancer.

  3. Influence of particle design on oral absorption of poorly water-soluble drug in a silica particle-supercritical fluid system.

    Science.gov (United States)

    Miura, Hiroshi; Kanebako, Makoto; Shirai, Hiroyuki; Nakao, Hiroshi; Inagi, Toshio; Terada, Katsuhide

    2011-01-01

    The physicochemical characteristics and oral absorption of a poorly water-soluble drug, K-832, adsorbed onto porous silica (Sylysia 350), were compared with those of K-832 adsorbed onto non-porous silica (Aerosil 200). K-832 and silica were treated with supercritical CO(2) (scCO(2)) to produce K-832-Sylysia 350 and K-832-Aerosil 200 formulations. Scanning electron microscopy, polarizing microscopy, powder X-ray diffraction, and differential scanning calorimetry results suggested that K-832 mainly existed in an amorphous state in both formulations. The specific surface area of both formulations was much larger than that of pure K-832 crystals. The dissolution rate of K-832 from both formulations was considerably greater than that from corresponding physical mixtures due to rapid wetting of the hydrophilic carrier surfaces and amorphous state, the dissolution from the K-832-Sylysia 350 formulation being the fastest. In vivo absorption tests on the two formulations indicated no significant differences in their peak concentration (C(max)) and the area under their plasma concentration-time curve (AUC), while the concentrations of K-832 in the K-832-Sylysia 350 formulation were significantly higher than those in the K-832-Aerosil 200 formulation 1 h and 1.5 h after administration of these formulations (ptests, the amorphous drugs in both formulations were stable at room temperature for at least 14 months. Thus, the absorption of poorly water-soluble drugs could be greatly improved by adsorption onto porous silica using scCO(2).

  4. Aqueous boundary layers related to oral absorption of a drug: from dissolution of a drug to carrier mediated transport and intestinal wall metabolism.

    Science.gov (United States)

    Sugano, Kiyohiko

    2010-10-04

    The aqueous boundary layer (ABL) affects various aspects of oral absorption of a drug, from dissolution of the drug to the apparent K(m) value of intestinal wall metabolism and carrier mediated transport. However, the importance of ABL has often been entirely ignored in oral absorption investigation. In this minireview, the effect of ABL on oral absorption of a drug is discussed in an easy-to-understand manner. This review starts with an introduction of the boundary layer theory with many illustrations (and links to public web movies visualizing the ABL), and then discusses some specific cases of interest in pharmaceutical science, such as dissolution of floating drug particles in the USP paddle apparatus. The effect of the boundary layer on the membrane permeation is also discussed from the viewpoint of structure permeability relationship, carrier mediated transport/metabolism and estimation of the fraction of a dose absorbed for poor solubility compounds.

  5. Hyperkalemia caused by rapid red cell transfusion and the potassium absorption filter

    Directory of Open Access Journals (Sweden)

    Yasuhiko Imashuku

    2017-01-01

    Full Text Available We report a case of transient hyperkalemia during hysterectomy after cesarean section, due to preoperatively undiagnosed placenta accreta that caused unforeseen massive hemorrhage and required rapid red cell transfusion. Hyperkalemia-induced by rapid red cell transfusion is a well-known severe complication of transfusion; however, in patients with sudden massive hemorrhage, rapid red cell transfusion is necessary to save their life. In such cases, it is extremely important to monitor serum potassium levels. For an emergency situation, a system should be developed to ensure sufficient preparation for immediate transfusion and laboratory tests. Furthermore, sufficient stock of preparations to treat hyperkalemia, such as calcium preparations, diuretics, glucose, and insulin is required. Moreover, a transfusion filter that absorbs potassium has been developed and is now available for clinical use in Japan. The filter is easy to use and beneficial, and should be prepared when it is available.

  6. Rapid enzymatic test for phenotypic HIV protease drug resistance

    OpenAIRE

    Hoffmann, D.; Assfalg-Machleidt, Irmgard; Nitschko, H; Helm, K. von der; Koszinowski, U.; Machleidt, Werner

    2003-01-01

    A phenotypic resistance test based on recombinant expression of the active HIV protease in E. coli from patient blood samples was developed. The protease is purified in a rapid onestep procedure as active enzyme and tested for inhibition by five selected synthetic inhibitors (amprenavir, indinavir, nelfinavir, ritonavir, and saquinavir) used presently for chemotherapy of HIVinfected patients. The HPLC system used in a previous approach was replaced by a continuous fluorogenic assay suitable f...

  7. Clinical significance of organic anion transporting polypeptides (OATPs) in drug disposition: their roles in hepatic clearance and intestinal absorption.

    Science.gov (United States)

    Shitara, Yoshihisa; Maeda, Kazuya; Ikejiri, Kazuaki; Yoshida, Kenta; Horie, Toshiharu; Sugiyama, Yuichi

    2013-01-01

    Organic anion transporting polypeptide (OATP) family transporters accept a number of drugs and are increasingly being recognized as important factors in governing drug and metabolite pharmacokinetics. OATP1B1 and OATP1B3 play an important role in hepatic drug uptake while OATP2B1 and OATP1A2 might be key players in intestinal absorption and transport across blood-brain barrier of drugs, respectively. To understand the importance of OATPs in the hepatic clearance of drugs, the rate-determining process for elimination should be considered; for some drugs, hepatic uptake clearance rather than metabolic intrinsic clearance is the more important determinant of hepatic clearances. The importance of the unbound concentration ratio (liver/blood), K(p,uu) , of drugs, which is partly governed by OATPs, is exemplified in interpreting the difference in the IC(50) of statins between the hepatocyte and microsome systems for the inhibition of HMG-CoA reductase activity. The intrinsic activity and/or expression level of OATPs are affected by genetic polymorphisms and drug-drug interactions. Their effects on the elimination rate or intestinal absorption rate of drugs may sometimes depend on the substrate drug. This is partly because of the different contribution of OATP isoforms to clearance or intestinal absorption. When the contribution of the OATP-mediated pathway is substantial, the pharmacokinetics of substrate drugs should be greatly affected. This review describes the estimation of the contribution of OATP1B1 to the total hepatic uptake of drugs from the data of fold-increases in the plasma concentration of substrate drugs by the genetic polymorphism of this transporter. To understand the importance of the OATP family transporters, modeling and simulation with a physiologically based pharmacokinetic model are helpful. Copyright © 2012 John Wiley & Sons, Ltd.

  8. Carbon Nanotube Micro-Needles for Rapid Transdermal Drug Delivery

    Science.gov (United States)

    Lyon, Bradley; Aria, Adrianus Indrat; Gat, Amir; Cosse, Julia; Montemayor, Lauren; Beizaie, Masoud; Gharib, Morteza

    2012-11-01

    By catalyst patterning, bundles of vertically-aligned carbon nanotubes (CNT) can be assembled to create 2D arrays of hollow micro-needles with feature size as small as a few microns. For transdermal drug delivery, the most challenging mechanical requirement is to make the CNT micro-needle small enough so that delivery is painless yet large enough so that the micro-needle can achieve skin penetration. By taking advantage of capillary action and the nanoporosity of CNT bundles, we can wick high strength polymer into the inter-spacing between nanotubes to augment the stiffness of our micro-needles. For low viscous polymers, the large ratio between the micron sized center hole of the micro-needle and the nanopores of the surrounding CNT allow us to wick polymer through the nanotubes while maintaining an open central hole for drug transport. For a transdermal patch prototype with a delivery area less than 1cm x 1cm square, we can fabricate 50 CNT micro-needles that produces a total flow rate up to 100 uL/s with actuation pressure provided by a mere finger tap. From in vitro experiments, we will demonstrate that CNT micro-needles provide a much faster convective delivery of drugs than conventional topical diffusion based patches. We acknowledge Zcube s.r.l for their support of this work.

  9. Methods of solving rapid binding target-mediated drug disposition model for two drugs competing for the same receptor.

    Science.gov (United States)

    Yan, Xiaoyu; Chen, Yang; Krzyzanski, Wojciech

    2012-10-01

    The target-mediated drug disposition (TMDD) model has been adopted to describe pharmacokinetics for two drugs competing for the same receptor. A rapid binding assumption introduces total receptor and total drug concentrations while free drug concentrations C (A) and C (B) are calculated from the equilibrium (Gaddum) equations. The Gaddum equations are polynomials in C (A) and C (B) of second degree that have explicit solutions involving complex numbers. The aim of this study was to develop numerical methods to solve the rapid binding TMDD model for two drugs competing for the same receptor that can be implemented in pharmacokinetic software. Algebra, calculus, and computer simulations were used to develop algorithms and investigate properties of solutions to the TMDD model with two drugs competitively binding to the same receptor. A general rapid binding approximation of the TMDD model for two drugs competing for the same receptor has been proposed. The explicit solutions to the equilibrium equations employ complex numbers, which cannot be easily solved by pharmacokinetic software. Numerical bisection algorithm and differential representation were developed to solve the system instead of obtaining an explicit solution. The numerical solutions were validated by MATLAB 7.2 solver for polynomial roots. The applicability of these algorithms was demonstrated by simulating concentration-time profiles resulting from exogenous and endogenous IgG competing for the neonatal Fc receptor (FcRn), and darbepoetin competing with endogenous erythropoietin for the erythropoietin receptor. These models were implemented in ADAPT 5 and Phoenix WinNonlin 6.0, respectively.

  10. [Inhibitory effect of nasal mucus on the absorption of drugs through respiratory epithelium].

    Science.gov (United States)

    Hayashi, H

    1990-01-01

    The absorption of Dibekacin (DKB) through rabbit's tracheal mucosa with and without nasal mucus were examined in vitro. The modified double chamber method was used for the purpose of this study. DKB solution (20 mg/ml) and Hanks' balanced salt solution were put into the donor compartment (DC) and the receiver compartment (RC), respectively. A plate with a hole and the tracheal mucosa were inserted between the compartments in the order of DC, dialytic membrane, the plate, the rabbit tracheal mucosa and RC. The hole of the plate was filled with nasal mucus or Hanks' solution. The latter was used as the control. The chamber was incubated in a humidified atmosphere of 5% CO2 in air for 3 hours at 37 degrees C. The absorption rate (AR) was obtained by dividing the concentration of DKB in RC by that in DC. The nasal mucus from patients with chronic sinusitis significantly decreased the AR of DKB compared with that in the control (P less than 0.05). The AR significantly decreased with increments in the thickness of nasal mucus by chronic sinusitis. This decreased AR was improved by the addition of N-Acetyl-L-cysteine (NAC) to DKB solution in DC. NAC can cleave disulfied bonds of mucus glycoprotein and this results in the decrease of viscoelasticity of nasal mucus. The results indicate that nasal mucus by chronic sinusitis intercept the absorption of drugs through respiratory epithelium in vitro. One of the mechanisms of the intercepter may be due to the high molecular-reticular structure of nasal mucus.

  11. The rule of unity for human intestinal absorption 2: application to pharmaceutical drugs that are marketed as salts.

    Science.gov (United States)

    Patel, Raj B; Admire, Brittany; Yalkowsky, Samuel H

    2015-01-01

    The efficiency of the human intestinal absorption (HIA) of the 59 drugs which are marketed as salts is predicted using the rule of unity. Intrinsic aqueous solubilities and partition coefficients along with the drug dose are used to calculate modified absorption potential (MAP) values. These values are shown to be related to the fraction of the dose that is absorbed upon oral administration in humans (FA). It is shown that the MAP value can distinguish between drugs that are poorly absorbed (FA drugs. This forms the basis of a simple rule of unity based solely on in vitro data for predicting whether or not a drug will be well absorbed at a given dose.

  12. A cluster randomised trial introducing rapid diagnostic tests into registered drug shops in Uganda

    DEFF Research Database (Denmark)

    Mbonye, Anthony K; Magnussen, Pascal; Lal, Sham

    2015-01-01

    the impact of introducing rapid diagnostic tests for malaria (mRDTs) in registered drug shops in Uganda, with the aim to increase appropriate treatment of malaria with artemisinin-based combination therapy (ACT) in patients seeking treatment for fever in drug shops. METHODS: A cluster-randomized trial...

  13. Rapid culture-based methods for drug-resistance detection in Mycobacterium tuberculosis.

    Science.gov (United States)

    Palomino, Juan Carlos; Martin, Anandi; Von Groll, Andrea; Portaels, Francoise

    2008-10-01

    Tuberculosis still represents a major public health problem, especially in low-resource countries where the burden of the disease is more important. Multidrug-resistant and extensively drug drug-resistant tuberculosis constitute serious problems for the efficient control of the disease stressing the need to investigate resistance to first- and second-line drugs. Conventional methods for detecting drug-resistance in Mycobacterium tuberculosis are slow and cumbersome. The most commonly used proportion method on Löwenstein-Jensen medium or Middlebrook agar requires a minimum of 3-4 weeks to produce results. Several new approaches have been proposed in the last years for the rapid and timely detection of drug-resistance in tuberculosis. This review will address phenotypic culture-based methods for rapid drug susceptibility testing in M. tuberculosis.

  14. The impact of urban particulate pollution on skin barrier function and the subsequent drug absorption.

    Science.gov (United States)

    Pan, Tai-Long; Wang, Pei-Wen; Aljuffali, Ibrahim A; Huang, Chi-Ting; Lee, Chiang-Wen; Fang, Jia-You

    2015-04-01

    Ambient particulate matters (PMs) are known as inducers that adversely affect a variety of human organs. In this study, we aimed to evaluate the influence of PMs on the permeation of drugs and sunscreens via the skin. The role of skin-barrier properties such as the stratum corneum (SC) and tight junctions (TJs) during the delivery process was explored. This work was conducted using both in vitro and in vivo experiments in pigs to check the responses of the skin to PMs. PMs primarily containing heavy metals (1648a) and polycyclic aromatic hydrocarbons (PAHs, 1649b) were employed to treat the skin. According to the transepidermal water loss (TEWL), 1649b but not 1648a significantly disrupted the SC integrity by 2-fold compared to the PBS control. The immunohistochemistry (IHC) of cytokeratin, filaggrin, and E-cadherin exhibited that 1649b mildly damaged TJs. The cytotoxicity of keratinocytes and skin fibroblasts caused by 1649b was stronger than that caused by 1648a. The 1649b elicited apoptosis via caspase-3 activation. The proteomic profiles showed that PMs upregulated Annexin A2 by >5-fold, which can be a biomarker of PM-induced barrier disruption. We found that the skin uptake of ascorbic acid, an extremely hydrophilic drug, was increased from 74 to 112 μg/g by 1649b treatment. The extremely lipophilic drug tretinoin also showed a 2.6-fold increase of skin accumulation. Oxybenzone and dextran absorption was not affected by PMs. The in vivo dye distribution visualized by fluorescence microscopy had indicated that 1649b intervention promoted permeant partitioning into SC. Caution should be taken in exposing the skin to airborne dust due to its ability to reduce barrier function and increase the risk of drug overabsorption, although this effect was not very marked. Copyright © 2015 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

  15. Microscopic Observation Drug Susceptibility Assay for Rapid Diagnosis of Lymph Node Tuberculosis and Detection of Drug Resistance.

    Science.gov (United States)

    Kirwan, Daniela E; Ugarte-Gil, Cesar; Gilman, Robert H; Caviedes, Luz; Rizvi, Hasan; Ticona, Eduardo; Chavez, Gonzalo; Cabrera, José Luis; Matos, Eduardo D; Evans, Carlton A; Moore, David A J; Friedland, Jon S

    2016-01-01

    In this study, 132 patients with lymphadenopathy were investigated. Fifty-two (39.4%) were diagnosed with tuberculosis (TB). The microscopic observation drug susceptibility (MODS) assay provided rapid (13 days), accurate diagnosis (sensitivity, 65.4%) and reliable drug susceptibility testing (DST). Despite its lower sensitivity than that of other methods, its faster results and simultaneous DST are advantageous in resource-poor settings, supporting the incorporation of MODS into diagnostic algorithms for extrapulmonary TB. Copyright © 2015 Kirwan et al.

  16. Soluplus® as an effective absorption enhancer of poorly soluble drugs in vitro and in vivo.

    Science.gov (United States)

    Linn, Michael; Collnot, Eva-Maria; Djuric, Dejan; Hempel, Katja; Fabian, Eric; Kolter, Karl; Lehr, Claus-Michael

    2012-02-14

    As many new active pharmaceutical ingredients are poorly water soluble, solubility enhancers are one possibility to overcome the hurdles of drug dissolution and absorption in oral drug delivery. In the present work a novel solubility enhancing excipient (Soluplus®) was tested for its capability to improve intestinal drug absorption. BCS class II compounds danazol, fenofibrate and itraconazole were tested both in vivo in beagle dogs and in vitro in transport experiments across Caco-2 cell monolayers. Each drug was applied as pure crystalline substance, in a physical mixture with Soluplus®, and as solid solution of the drug in the excipient. In the animal studies a many fold increase in plasma AUC was observed for the solid solutions of drug in Soluplus® compared to the respective pure drug. An effect of Soluplus® in a physical mixture with the drug could be detected for fenofibrate. In vitro transport studies confirm the strong effect of Soluplus® on the absorption behavior of the three tested drugs. Furthermore, the increase of drug flux across Caco-2 monolayer is correlating to the increase in plasma AUC and C(max)in vivo. For these poorly soluble substances Soluplus® has a strong potential to improve oral bioavailability. The applicability of Caco-2 monolayers as tool for predicting the in vivo transport behavior of the model drugs in combination with a solubility enhancing excipient was shown. Also the improvement of a solid dispersion compared to physical mixtures of the drugs and the excipient was correctly reflected by Caco-2 experiments. In the case of fenofibrate the possible improvement by a physical mixture was demonstrated, underscoring the value of the used tool as alternative to animal studies. Copyright © 2011 Elsevier B.V. All rights reserved.

  17. Rheological investigation and its correlation with permeability coefficient of drug loaded carbopol gel: influence of absorption enhancers.

    Science.gov (United States)

    Pisal, Prashant B; Patil, Sharvil S; Pokharkar, Varsha B

    2013-04-01

    The present study was planned to investigate the effect of absorption enhancers on the microstructure of Losartan potassium gel and hence its influence on the diffusion of Losartan potassium across nasal mucosa. Losartan potassium loaded carbopol gel (1% w/v) with and without absorption enhancers was prepared. Polyethylene glycol (PEG) 4000 and ethanol were used as absorption enhancers. Microstructural elucidation of prepared gels was done using shear rheology. Ex vivo drug release studies were performed on the prepared gels. It was observed that the absorption enhancers PEG 4000 and ethanol altered the gel microstructure. The prepared gels were viscoelastic in nature suggesting their suitability for topical application. Permeability coefficient of Losartan potassium loaded into gels was found to be inversely proportional to the storage modulus. Thus increase in storage modulus lead to slow drug diffusion. The current study emphasizes on the fact that selection of polymeric carrier for nasal drug delivery and/or absorption enhancer strongly influence the microstructure of the gel and hence the pharmaceutical performance of the formulation.

  18. Rapid identification of mycobacteria and rapid detection of drug resistance in Mycobacterium tuberculosis in cultured isolates and in respiratory specimens.

    Science.gov (United States)

    Yam, Wing-Cheong; Siu, Kit-Hang Gilman

    2013-01-01

    Recent advances in molecular biology and better understanding of the genetic basis of drug resistance have allowed rapid identification of mycobacteria and rapid detection of drug resistance of Mycobacterium tuberculosis present in cultured isolates or in respiratory specimens. In this chapter, several simple nucleic acid amplification-based techniques are introduced as molecular approach for clinical diagnosis of tuberculosis. A one-tube nested IS6110-based polymerase chain reaction (PCR) is used for M. tuberculosis complex identification; the use of a multiplex allele-specific PCR is demonstrated to detect the isoniazid resistance; PCR-sequencing assays are applied for rifampicin and ofloxacin resistance detection and 16S rDNA sequencing is utilized for identification of mycobacterial species from cultures of acid fast bacilli (AFB). Despite the high specificity and sensitivity of the molecular techniques, mycobacterial culture remains the "Gold Standard" for tuberculosis diagnosis. Negative results of molecular tests never preclude the infection or the presence of drug resistance. These technological advancements are, therefore, not intended to replace the conventional tests, but rather have major complementary roles in tuberculosis diagnosis.

  19. Novel oral formulation safely improving intestinal absorption of poorly absorbable drugs: utilization of polyamines and bile acids.

    Science.gov (United States)

    Miyake, Masateru; Minami, Takanori; Hirota, Masao; Toguchi, Hajime; Odomi, Masaaki; Ogawara, Ken-ichi; Higaki, Kazutaka; Kimura, Toshikiro

    2006-03-10

    In order to develop a novel oral formulation that can safely improve the intestinal absorption of poorly absorbable drugs, polyamines such as spermine (SPM) and spermidine (SPD) was examined as an absorption enhancing adjuvant in rats. The absorption of rebamipide, classified into BCS Class IV, from colon was significantly improved by SPM or SPD, and the enhancing ability of SPM was larger than that of SPD. As a possible mixing and/or interaction of polyamines with bile acids were expected, the combinatorial use of sodium taurocholate (STC) with polyamines was also examined. The absorption of rebamipide was drastically improved by the combinatorial use of SPM or SPD with STC. As STC itself did not enhance the absorption of rebamipide so much, it was considered that polyamines and STC had a synergistic enhancing effect. In-vivo oral absorption study was also performed to investigate the effectiveness and safety of polyamines and their combinatorial use with STC in rats. Although the enhancing effect slightly attenuated comparing with the in-situ loop study, the absorption of rebamipide was significantly improved and the combinatorial use of 10 mM SPM with 25 mM STC showed the largest enhancing effect. Histopathological studies clearly showed that any significant change in stomach and duodenum was not caused by SPM (10 mM), SPD (10 mM) or their combinatorial use with STC (25 mM) at 1.5 or 8.0 h after oral administration. Taken all together, polyamines, especially SPM, and its combinatorial use with STC could improve the absorption of poorly absorbable drugs without any significant changes in gastrointestinal tract after oral administration in rats.

  20. Time-resolved temperature measurements in a rapid compression machine using quantum cascade laser absorption in the intrapulse mode

    KAUST Repository

    Nasir, Ehson Fawad

    2016-07-16

    A temperature sensor based on the intrapulse absorption spectroscopy technique has been developed to measure in situ temperature time-histories in a rapid compression machine (RCM). Two quantum-cascade lasers (QCLs) emitting near 4.55μm and 4.89μm were operated in pulsed mode, causing a frequency "down-chirp" across two ro-vibrational transitions of carbon monoxide. The down-chirp phenomenon resulted in large spectral tuning (δν ∼2.8cm-1) within a single pulse of each laser at a high pulse repetition frequency (100kHz). The wide tuning range allowed the application of the two-line thermometry technique, thus making the sensor quantitative and calibration-free. The sensor was first tested in non-reactive CO-N2 gas mixtures in the RCM and then applied to cases of n-pentane oxidation. Experiments were carried out for end of compression (EOC) pressures and temperatures ranging 9.21-15.32bar and 745-827K, respectively. Measured EOC temperatures agreed with isentropic calculations within 5%. Temperature rise measured during the first-stage ignition of n-pentane is over-predicted by zero-dimensional kinetic simulations. This work presents, for the first time, highly time-resolved temperature measurements in reactive and non-reactive rapid compression machine experiments. © 2016 Elsevier Ltd.

  1. Real-time PCR using mycobacteriophage DNA for rapid phenotypic drug susceptibility results for Mycobacterium tuberculosis.

    Science.gov (United States)

    Pholwat, Suporn; Ehdaie, Beeta; Foongladda, Suporn; Kelly, Kimberly; Houpt, Eric

    2012-03-01

    Managing drug-resistant Mycobacterium tuberculosis requires drug susceptibility testing, yet conventional drug susceptibility testing is slow, and molecular testing does not yield results for all antituberculous drugs. We addressed these challenges by utilizing real-time PCR of mycobacteriophage D29 DNA to evaluate the drug resistance of clinical M. tuberculosis isolates. Mycobacteriophages infect and replicate in viable bacterial cells faster than bacterial cells replicate and have been used for detection and drug resistance testing for M. tuberculosis either by using reporter cells or phages with engineered reporter constructs. Our primary protocol involved culturing M. tuberculosis isolates for 48 h with and without drugs at critical concentrations, followed by incubation with 10(3) PFU/ml of D29 mycobacteriophage for 24 h and then real-time PCR. Many drugs could be incubated instantly with M. tuberculosis and phage for 24 h alone. The change in phage DNA real-time PCR cycle threshold (C(T)) between control M. tuberculosis and M. tuberculosis treated with drugs was calculated and correlated with conventional agar proportion drug susceptibility results. Specifically, 9 susceptible clinical isolates, 22 multidrug-resistant (MDR), and 1 extensively drug-resistant (XDR) M. tuberculosis strains were used and C(T) control-C(T) drug cutoffs of between +0.3 and -6.0 yielded 422/429 (98%) accurate results for isoniazid, rifampin, streptomycin, ethambutol, amikacin, kanamycin, capreomycin, ofloxacin, moxifloxacin, ethionamide, para-aminosalicylic acid, cycloserine, and linezolid. Moreover, the ΔC(T) values correlated with isolate MIC for most agents. This D29 quantitative PCR assay offers a rapid, accurate, 1- to 3-day phenotypic drug susceptibility test for first- and second-line drugs and may suggest an approximate MIC.

  2. An In Vivo Platform for Rapid High-Throughput Antitubercular Drug Discovery

    Directory of Open Access Journals (Sweden)

    Kevin Takaki

    2012-07-01

    Full Text Available Treatment of tuberculosis, like other infectious diseases, is increasingly hindered by the emergence of drug resistance. Drug discovery efforts would be facilitated by facile screening tools that incorporate the complexities of human disease. Mycobacterium marinum-infected zebrafish larvae recapitulate key aspects of tuberculosis pathogenesis and drug treatment. Here, we develop a model for rapid in vivo drug screening using fluorescence-based methods for serial quantitative assessment of drug efficacy and toxicity. We provide proof-of-concept that both traditional bacterial-targeting antitubercular drugs and newly identified host-targeting drugs would be discovered through the use of this model. We demonstrate the model’s utility for the identification of synergistic combinations of antibacterial drugs and demonstrate synergy between bacterial- and host-targeting compounds. Thus, the platform can be used to identify new antibacterial agents and entirely new classes of drugs that thwart infection by targeting host pathways. The methods developed here should be widely applicable to small-molecule screens for other infectious and noninfectious diseases.

  3. Paracetamol as a Post Prandial Marker for Gastric Emptying, A Food-Drug Interaction on Absorption.

    Science.gov (United States)

    Bartholomé, R; Salden, B; Vrolijk, M F; Troost, F J; Masclee, A; Bast, A; Haenen, G R

    2015-01-01

    The use of paracetamol as tool to determine gastric emptying was evaluated in a cross over study. Twelve healthy volunteers were included and each of them consumed two low and two high caloric meals. Paracetamol was mixed with a liquid meal and administered by a nasogastric feeding tube. The post prandial paracetamol plasma concentration time curve in all participants and the paracetamol concentration in the stomach content in six participants were determined. It was found that after paracetamol has left the stomach, based on analysis of the stomach content, there was still a substantial rise in the plasma paracetamol concentration time curve. Moreover, the difference in gastric emptying between high and low caloric meals was missed using the plasma paracetamol concentration time curve. The latter curves indicate that (i) part of the paracetamol may leave the stomach much quicker than the meal and (ii) part of the paracetamol may be relatively slowly absorbed in the duodenum. This can be explained by the partition of the homogenous paracetamol-meal mixture in the stomach in an aqueous phase and a solid bolus. The aqueous phase leaves the stomach quickly and the paracetamol in this phase is quickly absorbed in the duodenum, giving rise to the relatively steep increase of the paracetamol concentration in the plasma. The bolus leaves the stomach relatively slowly, and encapsulation by the bolus results in relatively slow uptake of paracetamol from the bolus in the duodenum. These findings implicate that paracetamol is not an accurate post prandial marker for gastric emptying. The paracetamol concentration time curve rather illustrates the food-drug interaction on absorption, which is not only governed by gastric emptying. ClinicalTrials.gov NCT01335503 Nederlands Trial Register NTR2780.

  4. Rapid identification of antifungal compounds against Exserohilum rostratum using high throughput drug repurposing screens.

    Science.gov (United States)

    Sun, Wei; Park, Yoon-Dong; Sugui, Janyce A; Fothergill, Annette; Southall, Noel; Shinn, Paul; McKew, John C; Kwon-Chung, Kyung J; Zheng, Wei; Williamson, Peter R

    2013-01-01

    A recent large outbreak of fungal infections by Exserohilum rostratum from contaminated compounding solutions has highlighted the need to rapidly screen available pharmaceuticals that could be useful in therapy. The present study utilized two newly-developed high throughput assays to screen approved drugs and pharmaceutically active compounds for identification of potential antifungal agents. Several known drugs were found that have potent effects against E. rostratum including the triazole antifungal posaconazole. Posaconazole is likely to be effective against infections involving septic joints and may provide an alternative for refractory central nervous system infections. The anti-E. rostratum activities of several other drugs including bithionol (an anti-parasitic drug), tacrolimus (an immunosuppressive agent) and floxuridine (an antimetabolite) were also identified from the drug repurposing screens. In addition, activities of other potential antifungal agents against E. rostratum were excluded, which may avoid unnecessary therapeutic trials and reveals the limited therapeutic alternatives for this outbreak. In summary, this study has demonstrated that drug repurposing screens can be quickly conducted within a useful time-frame. This would allow clinical implementation of identified alternative therapeutics and should be considered as part of the initial public health response to new outbreaks or rapidly-emerging microbial pathogens.

  5. Rapid identification of antifungal compounds against Exserohilum rostratum using high throughput drug repurposing screens.

    Directory of Open Access Journals (Sweden)

    Wei Sun

    Full Text Available A recent large outbreak of fungal infections by Exserohilum rostratum from contaminated compounding solutions has highlighted the need to rapidly screen available pharmaceuticals that could be useful in therapy. The present study utilized two newly-developed high throughput assays to screen approved drugs and pharmaceutically active compounds for identification of potential antifungal agents. Several known drugs were found that have potent effects against E. rostratum including the triazole antifungal posaconazole. Posaconazole is likely to be effective against infections involving septic joints and may provide an alternative for refractory central nervous system infections. The anti-E. rostratum activities of several other drugs including bithionol (an anti-parasitic drug, tacrolimus (an immunosuppressive agent and floxuridine (an antimetabolite were also identified from the drug repurposing screens. In addition, activities of other potential antifungal agents against E. rostratum were excluded, which may avoid unnecessary therapeutic trials and reveals the limited therapeutic alternatives for this outbreak. In summary, this study has demonstrated that drug repurposing screens can be quickly conducted within a useful time-frame. This would allow clinical implementation of identified alternative therapeutics and should be considered as part of the initial public health response to new outbreaks or rapidly-emerging microbial pathogens.

  6. Use of refractometry and colorimetry as field methods to rapidly assess antimalarial drug quality.

    Science.gov (United States)

    Green, Michael D; Nettey, Henry; Villalva Rojas, Ofelia; Pamanivong, Chansapha; Khounsaknalath, Lamphet; Grande Ortiz, Miguel; Newton, Paul N; Fernández, Facundo M; Vongsack, Latsamy; Manolin, Ot

    2007-01-04

    The proliferation of counterfeit and poor-quality drugs is a major public health problem; especially in developing countries lacking adequate resources to effectively monitor their prevalence. Simple and affordable field methods provide a practical means of rapidly monitoring drug quality in circumstances where more advanced techniques are not available. Therefore, we have evaluated refractometry, colorimetry and a technique combining both processes as simple and accurate field assays to rapidly test the quality of the commonly available antimalarial drugs; artesunate, chloroquine, quinine, and sulfadoxine. Method bias, sensitivity, specificity and accuracy relative to high-performance liquid chromatographic (HPLC) analysis of drugs collected in the Lao PDR were assessed for each technique. The HPLC method for each drug was evaluated in terms of assay variability and accuracy. The accuracy of the combined method ranged from 0.96 to 1.00 for artesunate tablets, chloroquine injectables, quinine capsules, and sulfadoxine tablets while the accuracy was 0.78 for enterically coated chloroquine tablets. These techniques provide a generally accurate, yet simple and affordable means to assess drug quality in resource-poor settings.

  7. A simple, rapid, and sensitive system for the evaluation of anti-viral drugs in rats

    Energy Technology Data Exchange (ETDEWEB)

    Li, Xiaoguang [Tohoku University Graduate School of Medicine, Department of Internal Medicine/Division of Emerging Infectious Diseases, Sendai 980-8575 (Japan); Department of Medical Microbiology, Harbin Medical University, Harbin 150086 (China); Center for AIDS Research, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811 (Japan); Qian, Hua [Tohoku University Graduate School of Medicine, Department of Internal Medicine/Division of Emerging Infectious Diseases, Sendai 980-8575 (Japan); Center for AIDS Research, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811 (Japan); Miyamoto, Fusako [Tohoku University Graduate School of Medicine, Department of Internal Medicine/Division of Emerging Infectious Diseases, Sendai 980-8575 (Japan); Naito, Takeshi [Laboratory of Virus Control, Institute for Virus Research, Kyoto University, 53 Kawaramachi, Shogoin, Sakyo-ku, Kyoto 606-8507 (Japan); Kawaji, Kumi [Tohoku University Graduate School of Medicine, Department of Internal Medicine/Division of Emerging Infectious Diseases, Sendai 980-8575 (Japan); Kajiwara, Kazumi [Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501 (Japan); JST Innovation Plaza Kyoto, Japan Science and Technology Agency, Nishigyo-ku, Kyoto 615-8245 (Japan); Hattori, Toshio [Tohoku University Graduate School of Medicine, Department of Internal Medicine/Division of Emerging Infectious Diseases, Sendai 980-8575 (Japan); Matsuoka, Masao [Laboratory of Virus Control, Institute for Virus Research, Kyoto University, 53 Kawaramachi, Shogoin, Sakyo-ku, Kyoto 606-8507 (Japan); Watanabe, Kentaro; Oishi, Shinya; Fujii, Nobutaka [Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501 (Japan); and others

    2012-07-27

    Highlights: Black-Right-Pointing-Pointer We established a novel, simple and rapid in vivo system for evaluation of anti-HIV-1 drugs with rats. Black-Right-Pointing-Pointer The system may be applicable for other antiviral drugs, and/or useful for initial screening in vivo. Black-Right-Pointing-Pointer In this system, TRI-1144 displayed the most potent anti-HIV-1 activity in vivo. -- Abstract: The lack of small animal models for the evaluation of anti-human immunodeficiency virus type 1 (HIV-1) agents hampers drug development. Here, we describe the establishment of a simple and rapid evaluation system in a rat model without animal infection facilities. After intraperitoneal administration of test drugs to rats, antiviral activity in the sera was examined by the MAGI assay. Recently developed inhibitors for HIV-1 entry, two CXCR4 antagonists, TF14016 and FC131, and four fusion inhibitors, T-20, T-20EK, SC29EK, and TRI-1144, were evaluated using HIV-1{sub IIIB} and HIV-1{sub BaL} as representative CXCR4- and CCR5-tropic HIV-1 strains, respectively. CXCR4 antagonists were shown to only possess anti-HIV-1{sub IIIB} activity, whereas fusion inhibitors showed both anti-HIV-1{sub IIIB} and anti-HIV-1{sub BaL} activities in rat sera. These results indicate that test drugs were successfully processed into the rat sera and could be detected by the MAGI assay. In this system, TRI-1144 showed the most potent and sustained antiviral activity. Sera from animals not administered drugs showed substantial anti-HIV-1 activity, indicating that relatively high dose or activity of the test drugs might be needed. In conclusion, the novel rat system established here, 'phenotypic drug evaluation', may be applicable for the evaluation of various antiviral drugs in vivo.

  8. Comparison of Deconvolution-Based and Absorption Modeling IVIVC for Extended Release Formulations of a BCS III Drug Development Candidate

    OpenAIRE

    Kesisoglou, Filippos; Xia, Binfeng; Agrawal, Nancy G. B.

    2015-01-01

    In vitro–in vivo correlations (IVIVC) are predictive mathematical models describing the relationship between dissolution and plasma concentration for a given drug compound. The traditional deconvolution/convolution-based approach is the most common methodology to establish a level A IVIVC that provides point to point relationship between the in vitro dissolution and the in vivo input rate. The increasing application of absorption physiologically based pharmacokinetic model (PBPK) has provided...

  9. TranScreen-N: Method for rapid screening of trans-ungual drug delivery enhancers.

    Science.gov (United States)

    Murthy, S Narasimha; Vaka, Siva Ram Kiran; Sammeta, Srinivasa Murthy; Nair, Anroop B

    2009-11-01

    Topical monotherapy of nail diseases such as onychomycosis and nail psoriasis has been less successful due to poor permeability of the human nail plate to topically administered drugs. Chemical enhancers are utilized to improve the drug delivery across the nail plate. Choosing the most effective chemical enhancers for the given drug and formulation is highly critical in determining the efficacy of topical therapy of nail diseases. Screening the large pool of enhancers using currently followed diffusion cell experiments would be tedious and expensive. The main objective of this study is to develop TranScreen-N, a high throughput method of screening trans-ungual drug permeation enhancers. It is a rapid microwell plate based method which involves two different treatment procedures; the simultaneous exposure treatment and the sequential exposure treatment. In the present study, several chemicals were evaluated by TranScreen-N and by diffusion studies in the Franz diffusion cell (FDC). Good agreement of in vitro drug delivery data with TranScreen-N data provided validity to the screening technique. In TranScreen-N technique, the enhancers can be grouped according to whether they need to be applied before or simultaneously with drugs (or by either procedures) to enhance the drug delivery across the nail plate. TranScreen-N technique can significantly reduce the cost and duration required to screen trans-ungual drug delivery enhancers. (c) 2009 Wiley-Liss, Inc. and the American Pharmacists Association

  10. Introducing rapid diagnostic tests for malaria into registered drug shops in Uganda

    DEFF Research Database (Denmark)

    Mbonye, Anthony K; Clarke, Sîan E; Lal, Sham

    2015-01-01

    BACKGROUND: Malaria is a major public health problem in Uganda and the current policy recommends introduction of rapid diagnostic tests for malaria (RDTs) to facilitate effective case management. However, provision of RDTs in drug shops potentially raises a new set of issues, such as adherence...... to RDTs results, management of severe illnesses, referral of patients, and relationship with caretakers. The main objective of the study was to examine the impact of introducing RDTs in registered drug shops in Uganda and document lessons and policy implications for future scale-up of malaria control...... in the private health sector. METHODS: A cluster-randomized trial introducing RDTs into registered drug shops was implemented in central Uganda from October 2010 to July 2012. An evaluation was undertaken to assess the impact and the processes involved with the introduction of RDTs into drug shops, the lessons...

  11. Rapid characterization of the biomechanical properties of drug-treated cells in a microfluidic device

    Science.gov (United States)

    Zhang, Xiaofei; Chu, Henry K.; Zhang, Yang; Bai, Guohua; Wang, Kaiqun; Tan, Qiulin; Sun, Dong

    2015-10-01

    Cell mechanics is closely related to many cell functions. Recent studies have suggested that the deformability of cells can be an effective biomarker to indicate the onset and progression of diseases. In this paper, a microfluidic chip is designed for rapid characterization of the mechanics of drug-treated cells through stretching with dielectrophoresis (DEP) force. This chip was fabricated using PDMS and micro-electrodes were integrated and patterned on the ITO layer of the chip. Leukemia NB4 cells were considered and the effect of all-trans retinoic acid (ATRA) drug on NB4 cells were examined via the microfluidic chip. To induce a DEP force onto the cell, a relatively weak ac voltage was utilized to immobilize a cell at one side of the electrodes. The applied voltage was then increased to 3.5 V pp and the cell started to be stretched along the applied electric field lines. The elongation of the cell was observed using an optical microscope and the results showed that both types of cells were deformed by the induced DEP force. The strain of the NB4 cell without the drug treatment was recorded to be about 0.08 (time t = 180 s) and the drug-treated NB4 cell was about 0.21 (time t = 180 s), indicating a decrease in the stiffness after drug treatment. The elastic modulus of the cell was also evaluated and the modulus changed from 140 Pa to 41 Pa after drug treatment. This microfluidic chip can provide a simple and rapid platform for measuring the change in the biomechanical properties of cells and can potentially be used as the tool to determine the biomechanical effects of different drug treatments for drug discovery and development applications.

  12. A Microfluidic Channel Method for Rapid Drug-Susceptibility Testing of Pseudomonas aeruginosa

    Science.gov (United States)

    Matsumoto, Yoshimi; Grushnikov, Andrey; Kikuchi, Kazuma; Noji, Hiroyuki; Yamaguchi, Akihito; Yagi, Yasushi

    2016-01-01

    The recent global increase in the prevalence of antibiotic-resistant bacteria and lack of development of new therapeutic agents emphasize the importance of selecting appropriate antimicrobials for the treatment of infections. However, to date, the development of completely accelerated drug susceptibility testing methods has not been achieved despite the availability of a rapid identification method. We proposed an innovative rapid method for drug susceptibility testing for Pseudomonas aeruginosa that provides results within 3 h. The drug susceptibility testing microfluidic (DSTM) device was prepared using soft lithography. It consisted of five sets of four microfluidic channels sharing one inlet slot, and the four channels are gathered in a small area, permitting simultaneous microscopic observation. Antimicrobials were pre-introduced into each channel and dried before use. Bacterial suspensions in cation-adjusted Mueller–Hinton broth were introduced from the inlet slot and incubated for 3 h. Susceptibilities were microscopically evaluated on the basis of differences in cell numbers and shapes between drug-treated and control cells, using dedicated software. The results of 101 clinically isolated strains of P. aeruginosa obtained using the DSTM method strongly correlated with results obtained using the ordinary microbroth dilution method. Ciprofloxacin, meropenem, ceftazidime, and piperacillin caused elongation in susceptible cells, while meropenem also induced spheroplast and bulge formation. Morphological observation could alternatively be used to determine the susceptibility of P. aeruginosa to these drugs, although amikacin had little effect on cell shape. The rapid determination of bacterial drug susceptibility using the DSTM method could also be applicable to other pathogenic species, and it could easily be introduced into clinical laboratories without the need for expensive instrumentation. PMID:26872134

  13. A Microfluidic Channel Method for Rapid Drug-Susceptibility Testing of Pseudomonas aeruginosa.

    Directory of Open Access Journals (Sweden)

    Yoshimi Matsumoto

    Full Text Available The recent global increase in the prevalence of antibiotic-resistant bacteria and lack of development of new therapeutic agents emphasize the importance of selecting appropriate antimicrobials for the treatment of infections. However, to date, the development of completely accelerated drug susceptibility testing methods has not been achieved despite the availability of a rapid identification method. We proposed an innovative rapid method for drug susceptibility testing for Pseudomonas aeruginosa that provides results within 3 h. The drug susceptibility testing microfluidic (DSTM device was prepared using soft lithography. It consisted of five sets of four microfluidic channels sharing one inlet slot, and the four channels are gathered in a small area, permitting simultaneous microscopic observation. Antimicrobials were pre-introduced into each channel and dried before use. Bacterial suspensions in cation-adjusted Mueller-Hinton broth were introduced from the inlet slot and incubated for 3 h. Susceptibilities were microscopically evaluated on the basis of differences in cell numbers and shapes between drug-treated and control cells, using dedicated software. The results of 101 clinically isolated strains of P. aeruginosa obtained using the DSTM method strongly correlated with results obtained using the ordinary microbroth dilution method. Ciprofloxacin, meropenem, ceftazidime, and piperacillin caused elongation in susceptible cells, while meropenem also induced spheroplast and bulge formation. Morphological observation could alternatively be used to determine the susceptibility of P. aeruginosa to these drugs, although amikacin had little effect on cell shape. The rapid determination of bacterial drug susceptibility using the DSTM method could also be applicable to other pathogenic species, and it could easily be introduced into clinical laboratories without the need for expensive instrumentation.

  14. Rapid analysis of drug dissolution by paper spray ionization mass spectrometry.

    Science.gov (United States)

    Liu, Yang; Liu, Ning; Zhou, Ya-Nan; Lin, Lan; He, Lan

    2017-03-20

    With a great quantity of solid dosage tested by dissolution technology, developing a rapid and sensitive method to access the content of drug within dissolution media is highly desired by analysts and scientists. Traditionally, dissolution media is not compatible with mass spectrometry since the inorganic salts in the media might damage the mass spectrometer. Here, paper spray ionization mass spectrometry (PSI-MS), one of the ambient mass spectrometry technologies, is developed to characterize the content of drugs in dissolution media. The porous structure of paper can effectively retain salts from entering mass spectrometer. This makes the measurement of drug content within dissolution media by mass spectrometer possible. After the experimental parameters were optimized, calibration curves of model drugs - enalapril, quinapril and benazepril were established by using corresponding deuterated internal standards. PSI-MS was then deployed to characterize the content of enalapril from the dissolution testing of enalapril tablets. The results from PSI-MS are comparable to those from HPLC characterization. More importantly, the analysis time of 6 samples is shortened from 90min to 6min. Detection limit of enalapril maleate tablets by PSI-MS is 1/300 of LC. PSI-MS is rapid, sensitive and accurate in analyzing drug content from dissolution tests. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Formulation of 3D Printed Tablet for Rapid Drug Release by Fused Deposition Modeling (FDM): Screening Polymers for Drug Release, Drug-Polymer Miscibility and Printability.

    Science.gov (United States)

    Solanki, Nayan; Tahsin, Md; Shah, Ankita; Serajuddin, Abu T M

    2017-10-21

    The primary aim of this study was to identify pharmaceutically acceptable amorphous polymers for producing 3D printed tablets of a model drug, haloperidol, for rapid release by fused deposition modeling (FDM). Filaments for 3D printing were prepared by hot melt extrusion at 150°C with 10 and 20% w/w of haloperidol using Kollidon(®) VA64, Kollicoat(®) IR, Affinsiol(™)15 cP and HPMCAS either individually or as binary blends (Kollidon(®) VA64+Affinisol(™)15 cP, 1:1; Kollidon(®) VA64+HPMCAS, 1:1). Dissolution of crushed extrudates was studied at pH 2 and 6.8, and formulations demonstrating rapid dissolution rates were then analyzed for drug-polymer, polymer-polymer and drug-polymer-polymer miscibility by film casting. Polymer-polymer (1:1) and drug-polymer-polymer (1:5:5 and 2:5:5) mixtures were found to be miscible. Tablets with 100 and 60 % infill were printed using MakerBot printer at 210°C, and dissolution tests of tablets were conducted at pH 2 and 6.8. Extruded filaments of Kollidon(®) VA64-Affinisol(™)15 cP mixtures were flexible and had optimum mechanical strength for 3D printing. Tablets containing 10% drug with 60 and 100% infill showed complete drug release at pH 2 in 45 and 120 min, respectively. Relatively high dissolution rates were also observed at pH 6.8. The 1:1-mixture of Kollidon(®) VA64 and Affinisol(™)15 cP was thus identified as a suitable polymer system for 3D printing and rapid drug release. Copyright © 2017. Published by Elsevier Inc.

  16. Introducing rapid diagnostic tests for malaria into drug shops in Uganda

    DEFF Research Database (Denmark)

    Mbonye, Anthony K; Magnussen, Pascal; Chandler, Clare Ir

    2014-01-01

    BACKGROUND: An intervention was designed to introduce rapid diagnostics tests for malaria (mRDTs) into registered drug shops in Uganda to encourage rational and appropriate treatment of malaria with artemisinin-based combination therapy (ACT). We conducted participatory training of drug shop...... through a cluster randomized trial. In this paper, we present detailed design, implementation and evaluation experiences in order to help inform future studies of a complex nature. METHODS: Three preparatory studies (formative, baseline and willingness-to-pay) were conducted to explore perceptions...

  17. Rapid detoxification of benzodiazepine or Z-drugs dependence using acetylcholinesterase inhibitors.

    Science.gov (United States)

    Lin, Shih-Ku

    2014-07-01

    Dependence on benzodiazepines (BZDs) or Z-drugs (zolpidem, zopicline and zaleplon) is a common clinical phenomenon. Traditional detoxification of BZDs dependence includes tapering used dose gradually and using equivalent doses of long-acting BZDs as substitutes. This kind of regimen tends to take a long time (up to 4weeks) and may require hospitalization. Acetylcholinesterase inhibitors have been shown to reverse BZDs induced sedation. We propose that oral form acetylcholinesterase inhibitors (donepezil, galantamine and rivastigmine) also posses the effect of inhibiting GABA receptors, and act as indirect antagonist, to be applied in the rapid detoxification treatment of BZDs and Z-drug dependence. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. A Comparative Study of Molecular Structure, pKa, Lipophilicity, Solubility, Absorption and Polar Surface Area of Some Antiplatelet Drugs

    Directory of Open Access Journals (Sweden)

    Milan Remko

    2016-03-01

    Full Text Available Theoretical chemistry methods have been used to study the molecular properties of antiplatelet agents (ticlopidine, clopidogrel, prasugrel, elinogrel, ticagrelor and cangrelor and several thiol-containing active metabolites. The geometries and energies of most stable conformers of these drugs have been computed at the Becke3LYP/6-311++G(d,p level of density functional theory. Computed dissociation constants show that the active metabolites of prodrugs (ticlopidine, clopidogrel and prasugrel and drugs elinogrel and cangrelor are completely ionized at pH 7.4. Both ticagrelor and its active metabolite are present at pH = 7.4 in neutral undissociated form. The thienopyridine prodrugs ticlopidine, clopidogrel and prasugrel are lipophilic and insoluble in water. Their lipophilicity is very high (about 2.5–3.5 logP values. The polar surface area, with regard to the structurally-heterogeneous character of these antiplatelet drugs, is from very large interval of values of 3–255 Å2. Thienopyridine prodrugs, like ticlopidine, clopidogrel and prasugrel, with the lowest polar surface area (PSA values, exhibit the largest absorption. A high value of polar surface area (PSA of cangrelor (255 Å2 results in substantial worsening of the absorption in comparison with thienopyridine drugs.

  19. Feasibility Study of Carbon Nanotube Microneedles for Rapid Transdermal Drug Delivery

    OpenAIRE

    Lyon, Bradley J.; Aria, Adrianus I.; Gharib, Morteza

    2013-01-01

    We introduce a new approach for fabricating hollow microneedles using vertically-aligned carbon nanotubes (VA-CNTs) for rapid transdermal drug delivery. Here, we discuss the fabrication of the microneedles emphasizing the overall simplicity and flexibility of the method to allow for potential industrial application. By capitalizing on the nanoporosity of the CNT bundles, uncured polymer can be wicked into the needles ultimately creating a high strength composite of aligned nanotubes and polym...

  20. Influence of the intermediate digestion phases of common formulation lipids on the absorption of a poorly water-soluble drug.

    Science.gov (United States)

    Kossena, Greg A; Charman, William N; Boyd, Ben J; Porter, Christopher J H

    2005-03-01

    The influence of different model intestinal phases (modelled on those likely to be produced in vivo after the digestion of commonly used formulation lipids) on the absorption profile of cinnarizine has been studied. Combinations of C8, C12, or C18:1 fatty acid and monoglyceride and simulated endogenous intestinal fluid were formulated to provide examples of liquid (L1), lamellar (L(alpha)), and cubic (C) liquid crystalline phases. Phases containing cinnarizine were dosed intraduodenally and absorption was assessed in an anesthetized rat model. Bile duct ligation was performed to inhibit the effects of digestion/dilution on the phase structure. Absorption from the L(alpha) phases (C8 and C12 lipids) was statistically higher (p precipitation of solubilized drug) and increasing in the case of the C18:1 C phase, possibly through the coexistence of L1 and C upon dilution permitting more efficient transfer of solubilized drug. Copyright 2004 Wiley-Liss, Inc. and the American Pharmacists Association.

  1. Rapid determination of anti-tuberculosis drug resistance from whole-genome sequences

    KAUST Repository

    Coll, Francesc

    2015-05-27

    Mycobacterium tuberculosis drug resistance (DR) challenges effective tuberculosis disease control. Current molecular tests examine limited numbers of mutations, and although whole genome sequencing approaches could fully characterise DR, data complexity has restricted their clinical application. A library (1,325 mutations) predictive of DR for 15 anti-tuberculosis drugs was compiled and validated for 11 of them using genomic-phenotypic data from 792 strains. A rapid online ‘TB-Profiler’ tool was developed to report DR and strain-type profiles directly from raw sequences. Using our DR mutation library, in silico diagnostic accuracy was superior to some commercial diagnostics and alternative databases. The library will facilitate sequence-based drug-susceptibility testing.

  2. Rapid, serial, non-invasive assessment of drug efficacy in mice with autoluminescent Mycobacterium ulcerans infection.

    Directory of Open Access Journals (Sweden)

    Tianyu Zhang

    Full Text Available Buruli ulcer (BU caused by Mycobacterium ulcerans is the world's third most common mycobacterial infection. There is no vaccine against BU and surgery is needed for patients with large ulcers. Although recent experience indicates combination chemotherapy with streptomycin and rifampin improves cure rates, the utility of this regimen is limited by the 2-month duration of therapy, potential toxicity and required parenteral administration of streptomycin, and drug-drug interactions caused by rifampin. Discovery and development of drugs for BU is greatly hampered by the slow growth rate of M. ulcerans, requiring up to 3 months of incubation on solid media to produce colonies. Surrogate markers for evaluating antimicrobial activity in real-time which can be measured serially and non-invasively in infected footpads of live mice would accelerate pre-clinical evaluation of new drugs to treat BU. Previously, we developed bioluminescent M. ulcerans strains, demonstrating proof of concept for measuring luminescence as a surrogate marker for viable M. ulcerans in vitro and in vivo. However, the requirement of exogenous substrate limited the utility of such strains, especially for in vivo experiments.For this study, we engineered M. ulcerans strains that express the entire luxCDABE operon and therefore are autoluminescent due to endogenous substrate production. The selected reporter strain displayed a growth rate and virulence similar to the wild-type parent strain and enabled rapid, real-time monitoring of in vitro and in vivo drug activity, including serial, non-invasive assessments in live mice, producing results which correlated closely with colony-forming unit (CFU counts for a panel of drugs with various mechanisms of action.Our results indicate that autoluminescent reporter strains of M. ulcerans are exceptional tools for pre-clinical evaluation of new drugs to treat BU due to their potential to drastically reduce the time, effort, animals, compound

  3. Modeling gastrointestinal drug absorption requires more in vivo biopharmaceutical data: experience from in vivo dissolution and permeability studies in humans.

    Science.gov (United States)

    Lennernäs, Hans

    2007-10-01

    The majority (84%) of the 50 most-sold pharmaceutical products in the US and European markets are given orally. The dominating role of this route in drug therapy is a consequence of it being safe, efficient and easily accessible with minimal discomfort to the patient in comparison with other routes of drug administration. A successful drug discovery and development of oral pharmaceutical products require an in-depth understanding of multiple biochemical and physiological processes that determine the dissolution rate, intestinal permeability, gastrointestinal transit, first-pass extraction and systemic exposure-time profiles of drugs. It is crucial to realize that these basic biopharmaceutic and pharmacokinetic properties are crucial to focus on to allow successful drug development. Identification of the rate-limiting step(s) in order to overcome these barriers and understanding of the sources of variability are important in the selection of suitable candidate molecules in drug development. Several reports based on in vitro investigations in various cell models have suggested that carrier-mediated intestinal efflux may be a major reason for incomplete absorption and variable bioavailability of drugs, as well being a site for drug-drug and specific food-drug interactions. However, many drugs which were initially suggested to undergo significant efflux in vitro were later shown to be completely absorbed in vivo. This apparent discrepancy between in vitro and in vivo results may be due to several factors that will be discussed in this review. Novel data on solubility and dissolution in human gastrointestinal derived fluids will be reviewed. The effect of food intake on solubility and dissolution rate of a range of drugs including felodipine, danazol, griseofulvin, cyclosporine, probucol and ubiquinone in simulated and real intestinal fluids is discussed. The biopharmaceutic and physicochemical data discussed here can potentially be used as a benchmark set for

  4. Administration of a probiotic can change drug pharmacokinetics: effect of E. coli Nissle 1917 on amidarone absorption in rats.

    Directory of Open Access Journals (Sweden)

    Zuzana Matuskova

    Full Text Available The growing interest in the composition and effects of microbiota raised the question how drug pharmacokinetics could be influenced by concomitant application of probiotics. The aim of this study was to find whether probiotic E. coli strain Nissle 1917 (EcN influences the pharmacokinetics of concomitantly taken antiarrhythmic drug amiodarone (AMI. Live bacterial suspension of probiotic EcN (or non-probiotic E. coli strain ATCC 25922 was applied orally to male Wistar rats for seven days, while a control group of rats was treated with a saline solution. On the eighth day, the amiodarone hydrochloride was administered as one single oral dose (50 mg/kg to all rats (N = 60. After 0, 1, 2, 3, 4, 5.5, 7, 9, 14, 22, and 30 hours, blood samples were taken from the rat abdominal aorta. The plasma level of AMI and its metabolite N-desethylamiodarone (DEA was determined using the HPLC with UV detection. Administration of EcN led to a 43% increase of AMI AUC0-30 in comparison with control samples. However, this effect was not observed if EcN was replaced by a reference non-probiotic E. coli strain. Thus, EcN administration was most probably responsible for better drug absorption from the gastrointestinal tract. Plasma levels of DEA were also increased in plasma samples from animals treated with EcN. This change was again not found in the experiment with the reference non-probiotic strain. Higher DEA levels in samples from EcN-treated rats may be explained either by better absorption of AMI and/or by an increased activity of CYP2C forms, known to participate in metabolism of this drug, after EcN administration. In this paper, it is documented that concomitantly taken probiotic EcN may modulate pharmacokinetics of a drug; in this case, it led to an increased bioavailability of AMI.

  5. In Silico Prediction of Drug Dissolution and Absorption with variation in Intestinal pH for BCS Class II Weak Acid Drugs: Ibuprofen and Ketoprofen§

    Science.gov (United States)

    Tsume, Yasuhiro; Langguth, Peter; Garcia-Arieta, Alfredo; Amidon, Gordon L.

    2012-01-01

    The FDA Biopharmaceutical Classification System guidance allows waivers for in vivo bioavailability and bioequivalence studies for immediate-release solid oral dosage forms only for BCS class I. Extensions of the in vivo biowaiver for a number of drugs in BCS Class III and BCS class II have been proposed, particularly, BCS class II weak acids. However, a discrepancy between the in vivo- BE results and in vitro- dissolution results for a BCS class II acids was recently observed. The objectives of this study were to determine the oral absorption of BCS class II weak acids via simulation software and to determine if the in vitro dissolution test with various dissolution media could be sufficient for in vitro bioequivalence studies of ibuprofen and ketoprofen as models of carboxylic acid drugs. The oral absorption of these BCS class II acids from the gastrointestinal tract was predicted by GastroPlus™. Ibuprofen did not satisfy the bioequivalence criteria at lower settings of intestinal pH=6.0. Further the experimental dissolution of ibuprofen tablets in the low concentration phosphate buffer at pH 6.0 (the average buffer capacity 2.2 mmol L-1/pH) was dramatically reduced compared to the dissolution in SIF (the average buffer capacity 12.6 mmol L -1/pH). Thus these predictions for oral absorption of BCS class II acids indicate that the absorption patterns largely depend on the intestinal pH and buffer strength and must be carefully considered for a bioequivalence test. Simulation software may be very useful tool to aid the selection of dissolution media that may be useful in setting an in vitro bioequivalence dissolution standard. PMID:22815122

  6. Novel atomic absorption spectrometric and rapid spectrophotometric methods for the quantitation of paracetamol in saliva: application to pharmacokinetic studies.

    Science.gov (United States)

    Issa, M M; Nejem, R M; El-Abadla, N S; Al-Kholy, M; Saleh, Akila A

    2008-01-01

    A novel atomic absorption spectrometric method and two highly sensitive spectrophotometric methods were developed for the determination of paracetamol. These techniques based on the oxidation of paracetamol by iron (III) (method I); oxidation of p-aminophenol after the hydrolysis of paracetamol (method II). Iron (II) then reacts with potassium ferricyanide to form Prussian blue color with a maximum absorbance at 700 nm. The atomic absorption method was accomplished by extracting the excess iron (III) in method II and aspirates the aqueous layer into air-acetylene flame to measure the absorbance of iron (II) at 302.1 nm. The reactions have been spectrometrically evaluated to attain optimum experimental conditions. Linear responses were exhibited over the ranges 1.0-10, 0.2-2.0 and 0.1-1.0 mug/ml for method I, method II and atomic absorption spectrometric method, respectively. A high sensitivity is recorded for the proposed methods I and II and atomic absorption spectrometric method value indicate: 0.05, 0.022 and 0.012 mug/ml, respectively. The limit of quantitation of paracetamol by method II and atomic absorption spectrometric method were 0.20 and 0.10 mug/ml. Method II and the atomic absorption spectrometric method were applied to demonstrate a pharmacokinetic study by means of salivary samples in normal volunteers who received 1.0 g paracetamol. Intra and inter-day precision did not exceed 6.9%.

  7. Rapid Identification of Potential Drugs for Diabetic Nephropathy Using Whole-Genome Expression Profiles of Glomeruli

    Directory of Open Access Journals (Sweden)

    Jingsong Shi

    2016-01-01

    Full Text Available Objective. To investigate potential drugs for diabetic nephropathy (DN using whole-genome expression profiles and the Connectivity Map (CMAP. Methodology. Eighteen Chinese Han DN patients and six normal controls were included in this study. Whole-genome expression profiles of microdissected glomeruli were measured using the Affymetrix human U133 plus 2.0 chip. Differentially expressed genes (DEGs between late stage and early stage DN samples and the CMAP database were used to identify potential drugs for DN using bioinformatics methods. Results. (1 A total of 1065 DEGs (FDR 1.5 were found in late stage DN patients compared with early stage DN patients. (2 Piperlongumine, 15d-PGJ2 (15-delta prostaglandin J2, vorinostat, and trichostatin A were predicted to be the most promising potential drugs for DN, acting as NF-κB inhibitors, histone deacetylase inhibitors (HDACIs, PI3K pathway inhibitors, or PPARγ agonists, respectively. Conclusion. Using whole-genome expression profiles and the CMAP database, we rapidly predicted potential DN drugs, and therapeutic potential was confirmed by previously published studies. Animal experiments and clinical trials are needed to confirm both the safety and efficacy of these drugs in the treatment of DN.

  8. Melanin binding study of clinical drugs with cassette dosing and rapid equilibrium dialysis inserts.

    Science.gov (United States)

    Pelkonen, Laura; Tengvall-Unadike, Unni; Ruponen, Marika; Kidron, Heidi; Del Amo, Eva M; Reinisalo, Mika; Urtti, Arto

    2017-11-15

    Melanin pigment is a negatively charged polymer found in pigmented human tissues. In the eye, iris, ciliary body, choroid and retinal pigment epithelium (RPE) are heavily pigmented. Several drug molecules are known to bind to melanin, but larger sets of drugs have not been compared often in similar test conditions. In this study, we introduce a powerful tool for screening of melanin binding. The binding of a set of 34 compounds to isolated porcine RPE melanin was determined by cassette (n-in-one) dosing in rapid equilibrium dialysis inserts and the binding was quantitated with LC-MS/MS analytics. The compounds represented large variety in melanin binding (from 8.6%, ganciclovir) to over 95% bound (ampicillin and ciprofloxacin). The data provides information on melanin binding of small molecular weight compounds that are used for ocular (e.g. brinzolamide, ganciclovir) and systemic (e.g. tizanidine, indomethacin) therapy. Interestingly, competition among compounds was seen for melanin binding and the binding did not show any correlation with plasma protein binding. These results increase the understanding of melanin binding of ocular drugs and can be further exploited to predict pharmacokinetics in the eye. Pigment binding provides an interesting option for improved drug distribution to retina and choroid that are difficult target tissues in drug delivery. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Rapid identification of a Mycobacterium tuberculosis full genetic drug resistance profile through whole genome sequencing directly from sputum

    Directory of Open Access Journals (Sweden)

    Camus Nimmo

    2017-09-01

    Discussion: Compared to rapid molecular tests (which can only examine a limited number of mutations and WGS of culture isolates (which requires a culture step, WGS directly from sputum can quickly generate a complete genetic drug resistance profile. In this case, WGS altered the clinical management of drug-resistant tuberculosis and demonstrated potential for guiding individualized drug treatment where second-line drug resistance is common.

  10. The effects of cyclodextrins on drugs absorption. I. In vitro observations

    NARCIS (Netherlands)

    Frijlink, H.W.; Schoonen, A.J.M.; Lerk, C.F.

    1989-01-01

    A two-phase transfer system, water with organic solvent, was used to investigate the effect of cyclodextrins on transport of dissolved lipophilic drugs from the aqueous to the organic layer. Four model drugs, diazepam, medazepam, n-butyl-p-aminobenzoate and n-pentyl-p-aminobenzoate were used.

  11. A Platform for Rapid, Quantitative Assessment of Multiple Drug Combinations Simultaneously in Solid Tumors In Vivo.

    Directory of Open Access Journals (Sweden)

    Joyoti Dey

    Full Text Available While advances in high-throughput screening have resulted in increased ability to identify synergistic anti-cancer drug combinations, validation of drug synergy in the in vivo setting and prioritization of combinations for clinical development remain low-throughput and resource intensive. Furthermore, there is currently no viable method for prospectively assessing drug synergy directly in human patients in order to potentially tailor therapies. To address these issues we have employed the previously described CIVO platform and developed a quantitative approach for investigating multiple combination hypotheses simultaneously in single living tumors. This platform provides a rapid, quantitative and cost effective approach to compare and prioritize drug combinations based on evidence of synergistic tumor cell killing in the live tumor context. Using a gemcitabine resistant model of pancreatic cancer, we efficiently investigated nine rationally selected Abraxane-based combinations employing only 19 xenografted mice. Among the drugs tested, the BCL2/BCLxL inhibitor ABT-263 was identified as the one agent that synergized with Abraxane® to enhance acute induction of localized apoptosis in this model of human pancreatic cancer. Importantly, results obtained with CIVO accurately predicted the outcome of systemic dosing studies in the same model where superior tumor regression induced by the Abraxane/ABT-263 combination was observed compared to that induced by either single agent. This supports expanded use of CIVO as an in vivo platform for expedited in vivo drug combination validation and sets the stage for performing toxicity-sparing drug combination studies directly in cancer patients with solid malignancies.

  12. Metabolic and drug distribution studies do not support direct inhibitory effects of metformin on intestinal glucose absorption.

    Science.gov (United States)

    Cuber, J C; Bosshard, A; Vidal, H; Vega, F; Wiernsperger, N; Rapin, J R

    1994-01-01

    In an attempt to clarify the question of an involvement of the inhibition of intestinal glucose absorption in the mechanism of action of Metformin, we used several experimental approaches: 1 glucose/lactate measurement in rat portal blood in vivo and 2 in the venous effluent of an isolated perfused rat intestinal segment; 3 metabolism of freshly isolated enterocytes in vitro and tissue distribution of 3H-labeled Metformin was investigated both in vivo and in vitro. Metformin applied intraluminally had no significant effect on portal glycaemia after a glucose load, but lactate increased, whereas in vivo only a high Metformin dosage reduced portal glucose appearance significantly. Although high Metformin concentrations were found in gut biopsies, precise histological analysis in the isolated intestine revealed that it was absent from enterocytes; however the drug accumulated in villous lacteals. Intrarterially applied Metformin decreased glucose absorption in the isolated perfused ileo-jejunal segment. These data suggested that vascular Metformin boosted intestinal anaerobic glucose metabolism. Biochemical measurements performed on freshly isolated enterocytes showed that even high Metformin levels did not interfere with cell respiration or with Na+/K+ ATPase activity. Thus, our data agree with other recent reports, suggesting that even at nontherapeutic concentrations Metformin has no relevant inhibitory effect on intestinal glucose absorption. The data are discussed in the frame of previous divergent observations. The results suggest however that Metformin of vascular origin stimulates glucose consumption by the intestine, which then increases lactate output from the gut.

  13. Systematic review of the performance of rapid rifampicin resistance testing for drug-resistant tuberculosis.

    Directory of Open Access Journals (Sweden)

    Matthew Arentz

    Full Text Available INTRODUCTION: Rapid tests for rifampicin resistance may be useful for identifying isolates at high risk of drug resistance, including multidrug-resistant TB (MDR-TB. However, choice of diagnostic test and prevalence of rifampicin resistance may both impact a diagnostic strategy for identifying drug resistant-TB. We performed a systematic review to evaluate the performance of WHO-endorsed rapid tests for rifampicin resistance detection. METHODS: We searched MEDLINE, Embase and the Cochrane Library through January 1, 2012. For each rapid test, we determined pooled sensitivity and specificity estimates using a hierarchical random effects model. Predictive values of the tests were determined at different prevalence rates of rifampicin resistance and MDR-TB. RESULTS: We identified 60 publications involving six different tests (INNO-LiPA Rif. TB assay, Genotype MTBDR assay, Genotype MTBDRplus assay, Colorimetric Redox Indicator (CRI assay, Nitrate Reductase Assay (NRA and MODS tests: for all tests, negative predictive values were high when rifampicin resistance prevalence was ≤ 30%. However, positive predictive values were considerably reduced for the INNO-LiPA Rif. TB assay, the MTBDRplus assay and MODS when rifampicin resistance prevalence was < 5%. LIMITATIONS: In many studies, it was unclear whether patient selection or index test performance could have introduced bias. In addition, we were unable to evaluate critical concentration thresholds for the colorimetric tests. DISCUSSION: Rapid tests for rifampicin resistance alone cannot accurately predict rifampicin resistance or MDR-TB in areas with a low prevalence of rifampicin resistance. However, in areas with a high prevalence of rifampicin resistance and MDR-TB, these tests may be a valuable component of an MDR-TB management strategy.

  14. Rapidly Progrediating Aortic Valve Infective Endocarditis in an Intravenous Drug User Treated by Antibiotics and Surgery

    Directory of Open Access Journals (Sweden)

    Malkia S. Swedi

    2012-01-01

    Full Text Available We report the case of a 22-year old male, a self-confessed recreational drug user who developed cardiogenic shock because of severe destruction of the aortic valve by rapidly progressive aortic valve endocarditis. The disease progression was acute; in a matter of days, the clinical manifestations were life-threatening necessitating urgent aortic valve replacement surgery. Cultivation revealed Streptococcus viridans as the microbial agent. Subsequent recovery with antibiotic treatment was without complication. This case report shows that immediately performed transoesophageal echocardiography and early consultation with a cardiac surgeon has fundamental importance in diagnosis and management of acute infective endocarditis in haemodynamically instable patients.

  15. Use of preclinical dog studies and absorption modeling to facilitate late stage formulation bridging for a BCS II drug candidate.

    Science.gov (United States)

    Kesisoglou, Filippos

    2014-02-01

    Formulation changes are common during drug development either due to clinical or manufacturing considerations. These changes especially at later stages of drug development oftentimes raise questions on the potential impact of a new formulation on bioavailability. In this work, the preclinical assessment of formulation bridging risk for a Biopharmaceutics Classification System II development compound is presented. Early clinical studies were conducted using a liquid-filled capsule (LFC). To assess the feasibility of a conventional solid dosage form, an initial analysis was conducted using absorption modeling which indicated conventional formulation of micronized active pharmaceutical ingredient (API) could be a viable option. Subsequently, test formulations were prepared and tested in vivo in dogs. The solid formulations were able to match exposures of the LFC capsule in the dog model; in addition, a sensitivity to API PSD was observed in line with the modeling predictions. When tested in the clinic, the conventional solid formulation resulted in exposures of approximately 25% lower compared to the LFC on an equivalent dose basis; however, bridging with a small dose adjustment would be feasible. The outcome of the clinical study was better predicted by the modeling approach while the dog model appeared to somewhat overestimate absorption. Through the use of preclinical tools and modeling and simulation, a risk assessment around formulation bridging can be conducted and inform formulation decisions or subsequent clinical study designs.

  16. Enhanced absorption of the poorly soluble drug fenofibrate by tuning its release rate from ordered mesoporous silica.

    Science.gov (United States)

    Van Speybroeck, Michiel; Mellaerts, Randy; Mols, Raf; Thi, Thao Do; Martens, Johan Adriaan; Van Humbeeck, Jan; Annaert, Pieter; Van den Mooter, Guy; Augustijns, Patrick

    2010-12-23

    The aim of the present study was to evaluate the effect of release rate from ordered mesoporous silica materials on the rate and extent of absorption of the poorly soluble drug fenofibrate. Three ordered mesoporous silica materials with different pore diameter (7.3 nm, 4.4 nm and 2.7 nm) were synthesized and loaded with fenofibrate via impregnation. Release experiments were conducted under sink conditions and under supersaturating conditions in biorelevant media, simulating the fasted and the fed state. Subsequently, all silica-based formulations were evaluated in vivo (rat model). The release experiments under sink conditions indicated a clear increase in release rate with increasing pore size. However, under supersaturating conditions (FaSSIF), the, pharmaceutical performance (in terms of both the degree and duration of supersaturation), increased with decreasing pore size. The same trend was observed in vivo (fasted state): the area under the plasma concentration-time profile amounted to 102 ± 34 μMh, 86 ± 19 μMh and 20 ± 13 μMh for the materials with pore diameter of 2.7 nm, 4.4 nm and 7.3 nm, respectively. The results of this, study demonstrate that a decrease in drug release rate - and thus, a decrease of the rate at which supersaturation is created - is beneficial to the absorption of fenofibrate. Copyright © 2010 Elsevier B.V. All rights reserved.

  17. Colorimetric and atomic absorption spectrometric determination of mucolytic drug ambroxol through ion-pair formation with iron and thiocyanate.

    Science.gov (United States)

    Levent, Abdulkadir; Sentürk, Zühre

    2010-09-01

    Colorimetric and atomic absorption spectrometric methods have been developed for the determination of mucolytic drug Ambroxol. These procedures depend upon the reaction of iron(III) metal ion with the drug in the presence of thiocyanate ion to form stable ion-pair complex which extractable chloroform. The red-coloured complex was determined either colorimetrically at 510 nm or by indirect atomic absorption spectrometry (AAS) via the determination of the iron content in the formed complex. The optimum experimental conditions for pH, concentrations of Fe(3+) and SCN(-), shaking time, phase ratio, and the number of extractions were determined. Under the proposed conditions, linearity was obeyed in the concentration ranges 4.1x10(-6) - 5.7x10(-5) M (1.7-23.6 µg mL(-1)) using both methods, with detection limits of 4.6x10(-7) M (0.19 µg mL(-1)) for colorimetry and 1.1x10(-6) M (0.46 µg mL(-1)) for AAS. The proposed methods were applied for the determination of Ambroxol in tablet dosage forms. The results obtained were statistically analyzed and compared with those obtained by applying the high-performance liquid chromatographic method with diode-array detection.

  18. Recent Advances in Delivery Systems and Therapeutics of Cinnarizine: A Poorly Water Soluble Drug with Absorption Window in Stomach

    Directory of Open Access Journals (Sweden)

    Smita Raghuvanshi

    2014-01-01

    Full Text Available Low solubility causing low dissolution in gastrointestinal tract is the major problem for drugs meant for systemic action after oral administration, like cinnarizine. Pharmaceutical products of cinnarizine are commercialized globally as immediate release preparations presenting low absorption with low and erratic bioavailability. Approaches to enhance bioavailability are widely cited in the literature. An attempt has been made to review the bioavailability complications and clinical therapeutics of poorly water soluble drug: cinnarizine. The interest of writing this paper is to summarize the pharmacokinetic limitations of drug with special focus on strategies to improvise bioavailability along with effectiveness of novel dosage forms to circumvent the obstacle. The paper provides insight to the approaches to overcome low and erratic bioavailability of cinnarizine by cyclodextrin complexes and novel dosage forms: self-nanoemulsifying systems and buoyant microparticulates. Nanoformulations need to systematically explored in future, for their new clinical role in prophylaxis of migraine attacks in children. Clinical reports have affirmed the role of cinnarizine in migraine prophylaxis. Research needs to be dedicated to develop dosage forms for efficacious bioavailability and drug directly to brain.

  19. Site-specific drug delivery to the middle-to-lower region of the small intestine reduces food-drug interactions that are responsible for low drug absorption in the fed state.

    Science.gov (United States)

    Tanno, Fumié K; Sakuma, Shinji; Masaoka, Yoshie; Kataoka, Makoto; Kozaki, Toshio; Kamaguchi, Ryosei; Ikeda, Yutaka; Kokubo, Hiroyasu; Yamashita, Shinji

    2008-12-01

    Food-drug interactions may reduce the bioavailability of drugs taken after meals (negative food effects). We designed enteric-coated tablets that start to disintegrate when they reach the middle-to-lower region of the small intestine, and examined whether they could reduce negative food effects in dogs. Tablets containing trientine as a model drug were coated with hypromellose acetate succinate (HPMCAS) with various values of succinoyl group content. The time lag of drug dissolution from these enteric-coated tablets in simulated intestinal fluid of pH 6.8 increased as the succinoyl group content was decreased. The AUC of trientine after oral administration of its aqueous solution to fed dogs was one-eighth of that in fasted dogs. The low drug absorption in fed dogs was improved when trientine was administered as enteric-coated tablets. The average ratio of AUC in the fed state to that in the fasted state increased with decreasing succinoyl group content of HPMCAS. Negative food effects completely disappeared after oral administration of tablets coated with HPMCAS having a succinoyl group content of 6.2% or less, which probably disintegrated in the middle-to-lower small intestine. Our results indicated that food-drug interactions were avoided by separating the main absorption site of drugs from that of food components.

  20. Percutaneous absorption and antibacterial activities of lipid nanocarriers loaded with dual drugs for acne treatment.

    Science.gov (United States)

    Lin, Chih-Hung; Fang, Yi-Ping; Al-Suwayeh, Saleh Abdulah; Yang, Shih-Yung; Fang, Jia-You

    2013-01-01

    The aim of this study was to develop lipid nanocarriers that combine tretinoin and tetracycline for the efficient topical delivery to treat acne vulgaris. Two different nanocarriers, nanoemulsions (NEs) and nanostructured lipid carriers (NLCs), were prepared, and we examined their average size, zeta potential, drug encapsulation percentage, and drug permeation via the skin. The antibacterial activities of the nanosystems against Staphylococcus aureus, Pseudomonas aeruginosa, and Propionibacterium acnes were evaluated by an agar diffusion assay and the amount of total protein. A ca. 200-nm particle size was achieved with the prepared nanoparticles. The size increased when incorporating a cationic surfactant. Dual-drug loading did not largely affect the size of negatively charged nanoparticles, but significantly reduced the particle size of positively charged nanocarriers. NEs and NLCs exhibited high entrapment of tretinoin which ranged 60-100%. Tetracycline mainly resided in the aqueous phase, with ca. 10% of molecules located at the particulate interface. An in vitro skin permeation study showed that NLCs enhanced tetracycline flux by about 2-times over the control solution. Tretinoin permeation was generally unaffected after nanoparticulate encapsulation. There was no significant difference in tretinoin delivery before or after tetracycline incorporation, while tetracycline permeation significantly decreased by 2-fold in the dual-drug system. Nanoparticulate loading mostly maintained the antibacterial activity of tetracycline. Negatively charged NEs and NLCs even strengthened the antibacterial ability against S. aureus compared to the control solution. This is the first report examining skin permeation and antibacterial activities of dual-drug nanocarriers for acne treatment.

  1. Small molecule absorption by PDMS in the context of drug response bioassays

    NARCIS (Netherlands)

    van Meer, B.J.; de Vries, H.; Firth, K.S.A.; van Weerd, Jasper; Tertoolen, L.G.J.; Karperien, Hermanus Bernardus Johannes; Jonkheijm, Pascal; Denning, C.; IJzerman, A.P.; Mummery, Christine Lindsay

    2017-01-01

    The polymer polydimethylsiloxane (PDMS) is widely used to build microfluidic devices compatible with cell culture. Whilst convenient in manufacture, PDMS has the disadvantage that it can absorb small molecules such as drugs. In microfluidic devices like "Organs-on-Chip", designed to examine cell

  2. Applying green analytical chemistry for rapid analysis of drugs: Adding health to pharmaceutical industry

    Directory of Open Access Journals (Sweden)

    Nazrul Haq

    2017-02-01

    Full Text Available Green RP-HPLC method for a rapid analysis of olmesartan medoxomil (OLM in bulk drugs, self-microemulsifying drug delivery system (SMEDDS and marketed tablets was developed and validated in the present investigation. The chromatographic identification was achieved on Lichrosphere 250 × 4.0 mm RP C8 column having a 5 μm packing as a stationary phase using a combination of green solvents ethyl acetate:ethanol (50:50% v/v as a mobile phase, at a flow rate of 1.0 mL/min with UV detection at 250 nm. The proposed method was validated for linearity, selectivity, accuracy, precision, reproducibility, robustness, sensitivity and specificity. The utility of the proposed method was verified by an assay of OLM in SMEDDS and commercial tablets. The proposed method was found to be selective, precise, reproducible, accurate, robust, sensitive and specific. The amount of OLM in SMEDDS and commercial tablets was found to be 101.25% and 98.67% respectively. The proposed method successfully resolved OLM peak in the presence of its degradation products which indicated stability-indicating property of the proposed method. These results indicated that the proposed method can be successfully employed for a routine analysis of OLM in bulk drugs and commercial formulations.

  3. Real time PCR for the rapid identification and drug susceptibility of Mycobacteria present in Bronchial washings

    Directory of Open Access Journals (Sweden)

    Thilini Piushani Keerthirathne

    2016-10-01

    Full Text Available Abstract Background Mycobacteria have a spectrum of virulence and different susceptibilities to antibiotics. Distinguishing mycobacterial species is vital as patients with non-tuberculous mycobacterial (NTM infections present clinical features that are similar to those of patients with tuberculosis. Thus, rapid differentiation of Mycobacterium tuberculosis complex from NTM is critical to administer appropriate treatment. Hence the aim of the study was to rapid identification of mycobacterial species present in bronchial washings using multiplex real time Polymerase Chain Reaction (PCR and to determine the drug susceptibility in identified mycobacterial species. Methods Sputum smear negative bronchoscopy specimens (n = 150 were collected for a period of one year, from patients attending the General Hospital Kandy, Sri Lanka. The specimens were processed with modified Petroff’s method and were cultured on Löwenstein– Jensen medium. DNA, extracted from the mycobacterial isolates were subjected to a SYBR green mediated real time multiplex, PCR assay with primers specific for the M. tuberculosis complex, M. avium complex, M. chelonae-M.abscessus group and M. fortuitum group. DNA sequencing was performed for the species confirmation, by targeting the 16S rRNA gene and the drug susceptibility testing was performed for the molecularly identified isolates of M. tuberculosis and NTM. Results The optimized SYBR Green mediated multiplex real-time PCR assay was able to identify the presence of genus Mycobacterium in 25 out of 26 AFB positive isolates, two M. tuberculosis complex, three M. avium complex and two isolates belonging to M. chelonae-M. abscessus group. DNA sequencing confirmed the presence of M. tuberculosis, M. chelonae-M. abscessus, M. intracellulare, M. avium, Rhodococcus sp. and M. celatum. Remaining isolates were identified as Mycobacterium sp. All the NTM isolates were sensitive to amikacin and seven were resistant to ciproflaxacin

  4. Drug-Related Hyponatremic Encephalopathy: Rapid Clinical Response Averts Life-Threatening Acute Cerebral Edema.

    Science.gov (United States)

    Siegel, Arthur J; Forte, Sophie S; Bhatti, Nasir A; Gelda, Steven E

    2016-03-09

    Drug-induced hyponatremia characteristically presents with subtle psychomotor symptoms due to its slow onset, which permits compensatory volume adjustment to hypo-osmolality in the central nervous system. Due mainly to the syndrome of inappropriate antidiuretic hormone secretion (SIADH), this condition readily resolves following discontinuation of the responsible pharmacological agent. Here, we present an unusual case of life-threatening encephalopathy due to adverse drug-related effects, in which a rapid clinical response facilitated emergent treatment to avert life-threatening acute cerebral edema. A 63-year-old woman with refractory depression was admitted for inpatient psychiatric care with a normal physical examination and laboratory values, including a serum sodium [Na+] of 144 mEq/L. She had a grand mal seizure and became unresponsive on the fourth day of treatment with the dual serotonin and norepinephrine reuptake inhibitor [SNRI] duloxetine while being continued on a thiazide-containing diuretic for a hypertensive disorder. Emergent infusion of intravenous hypertonic (3%) saline was initiated after determination of a serum sodium [Na+] of 103 mEq/L with a urine osmolality of 314 mOsm/kg H20 and urine [Na+] of 12 mEq/L. Correction of hyposmolality in accordance with current guidelines resulted in progressive improvement over several days, and she returned to her baseline mental status. Seizures with life-threatening hyponatremic encephalopathy in this case likely resulted from co-occurring SIADH and sodium depletion due to duloxetine and hydrochlorothiazide, respectively. A rapid clinical response expedited diagnosis and emergent treatment to reverse life-threatening acute cerebral edema and facilitate a full recovery without neurological complications.

  5. Reply to "On the Effect of Common Excipients on the Oral Absorption of Class 3 Drugs".

    Science.gov (United States)

    Vaithianathan, Soundarya; Haidar, Sam H; Zhang, Xinyuan; Jiang, Wenlei; Avon, Christopher; Dowling, Thomas C; Shao, Changxing; Kane, Maureen; Hoag, Stephen W; Flasar, Mark H; Ting, Tricia Y; Polli, James E

    2016-04-01

    We previously concluded that 12 common excipients need not be qualitatively the same and quantitatively very similar to reference for Biopharmaceutics Classification System-based biowaivers. This conclusion for regulatory relief is based upon a series of bioequivalence studies in humans involving cimetidine and acyclovir. Limitations were also discussed. We understand the major concern of García-Arieta et al. is that "results obtained by Vaithianathan et al. should not be extrapolated to other drugs." We understand that individuals conducting their own risk/benefit analysis may reach that conclusion, and we reply to the concerns of García-Arieta et al. We continue to conclude that the 12 common excipients need not be qualitatively the same nor quantitatively very similar to reference, but rather, simply be not more than the quantities studied in our manuscript for cimetidine and acyclovir, and potentially other class 3 drugs with similar properties. Copyright © 2016 American Pharmacists Association®. All rights reserved.

  6. In silico and in vitro prediction of gastrointestinal absorption from potential drug eremantholide C.

    Science.gov (United States)

    Caldeira, Tamires G; Saúde-Guimarães, Dênia A; Dezani, André B; Serra, Cristina Helena Dos Reis; de Souza, Jacqueline

    2017-11-01

    Analysis of the biopharmaceutical properties of eremantholide C, sesquiterpene lactone with proven pharmacological activity and low toxicity, is required to evaluate its potential to become a drug. Preliminary analysis of the physicochemical characteristics of eremantholide C was performed in silico. Equilibrium solubility was evaluated using the shake-flask method, at 37.0 °C, 100 rpm during 72 h in biorelevant media. The permeability was analysed using parallel artificial membrane permeability assay, at 37.0 °C, 50 rpm for 5 h. The donor compartment was composed of an eremantholide C solution in intestinal fluid simulated without enzymes, while the acceptor compartment consisted of phosphate buffer. Physicochemical characteristics predicted in silico indicated that eremantholide C has a low solubility and high permeability. In-vitro data of eremantholide C showed low solubility, with values for the dose/solubility ratio (ml): 9448.82, 10 389.61 e 15 000.00 for buffers acetate (pH 4.5), intestinal fluid simulated without enzymes (pH 6.8) and phosphate (pH 7.4), respectively. Also, it showed high permeability, with effective permeability of 30.4 × 10(-6) cm/s, a higher result compared with propranolol hydrochloride (9.23 × 10(-6) cm/s). The high permeability combined with its solubility, pharmacological activity and low toxicity demonstrate the importance of eremantholide C as a potential drug candidate. © 2017 Royal Pharmaceutical Society.

  7. Potential drug – nanosensor conjugates: Raman, infrared absorption, surface – enhanced Raman, and density functional theory investigations of indolic molecules

    Energy Technology Data Exchange (ETDEWEB)

    Pięta, Ewa, E-mail: Ewa.Pieta@ifj.edu.pl [Institute of Nuclear Physics, Polish Academy of Sciences, PL-31342 Krakow (Poland); Paluszkiewicz, Czesława [Institute of Nuclear Physics, Polish Academy of Sciences, PL-31342 Krakow (Poland); Oćwieja, Magdalena [J. Haber Institute of Catalysis and Surface Chemistry, Polish Academy of Sciences, PL-30239 Krakow (Poland); Kwiatek, Wojciech M. [Institute of Nuclear Physics, Polish Academy of Sciences, PL-31342 Krakow (Poland)

    2017-05-15

    Highlights: • Molecular fragments involved in the adsorption process were determined. • Formation of hydrogen bonds with the negatively charged gold substrates was observed. • Indole moiety strongly interacts with gold nanosensors. • The synthesized sensors are characterized by high stability and reproducibility. • Chemical mechanism plays a crucial role in the enhancement of the Raman signal. - Abstract: An extremely important aspect of planning cancer treatment is not only the drug efficiency but also a number of challenges associated with the side effects and control of this process. That is why it is worth paying attention to the promising potential of the gold nanoparticles combined with a compound treated as a potential drug. This work presents Raman (RS), infrared absorption (IR) and surface–enhanced Raman scattering (SERS) spectroscopic investigations of N–acetyl–5–methoxytryptamine (melatonin) and α–methyl–DL–tryptophan, regarding as anti breast cancer agents. The experimental spectroscopic analysis was supported by the quantum-chemical calculations based on the B3LYP hybrid density functional theory (DFT) at the B3LYP 6–311G(d,p) level of theory. The studied compounds were adsorbed onto two colloidal gold nanosensors synthesized by a chemical reduction method using sodium borohydride (SB) and trisodium citrate (TC), respectively. Its morphology characteristics were obtained using transmission electron microscopy (TEM). It has been suggested that the NH moiety from the aromatic ring, a well-known proton donor, causes the formation of hydrogen bonds with the negatively charged gold surface.

  8. Potential drug - nanosensor conjugates: Raman, infrared absorption, surface - enhanced Raman, and density functional theory investigations of indolic molecules

    Science.gov (United States)

    Pięta, Ewa; Paluszkiewicz, Czesława; Oćwieja, Magdalena; Kwiatek, Wojciech M.

    2017-05-01

    An extremely important aspect of planning cancer treatment is not only the drug efficiency but also a number of challenges associated with the side effects and control of this process. That is why it is worth paying attention to the promising potential of the gold nanoparticles combined with a compound treated as a potential drug. This work presents Raman (RS), infrared absorption (IR) and surface-enhanced Raman scattering (SERS) spectroscopic investigations of N-acetyl-5-methoxytryptamine (melatonin) and α-methyl-DL-tryptophan, regarding as anti breast cancer agents. The experimental spectroscopic analysis was supported by the quantum-chemical calculations based on the B3LYP hybrid density functional theory (DFT) at the B3LYP 6-311G(d,p) level of theory. The studied compounds were adsorbed onto two colloidal gold nanosensors synthesized by a chemical reduction method using sodium borohydride (SB) and trisodium citrate (TC), respectively. Its morphology characteristics were obtained using transmission electron microscopy (TEM). It has been suggested that the NH moiety from the aromatic ring, a well-known proton donor, causes the formation of hydrogen bonds with the negatively charged gold surface.

  9. Luminal leptin induces rapid inhibition of active intestinal absorption of glucose mediated by sodium-glucose cotransporter 1.

    Science.gov (United States)

    Ducroc, Robert; Guilmeau, Sandra; Akasbi, Khalil; Devaud, Hélène; Buyse, Marion; Bado, André

    2005-02-01

    The effect of leptin on glucose transport was studied in rat jejunal mucosa in Ussing chambers. Leptin was added in the luminal or the serosal compartment before the tissues were challenged with 1, 10, or 50 mmol/l glucose. In response to 10 mmol/l glucose, the increase in short-circuit current (DeltaIsc) reached 26.8 +/- 2.1 microA/cm(2). Luminal addition of leptin dramatically decreased glucose-induced Isc (90.5% for 10 nmol/l leptin). Inhibition was maximal after 5 min and dose dependent (IC(50) = 0.13 nM). Western blot analysis showed that rapid inhibition of glucose-induced Isc by leptin was associated with a parallel decrease in the abundance of sodium-glucose transporter-1 in brush border membranes. Inhibition by luminal leptin of DeltaIsc was prevented by inhibitor of conventional protein kinase C isoforms. Serosal addition of leptin did not decrease glucose-induced Isc within 5 min and reached maximum after 10 min. The effect of leptin from serosal side was blocked by cholecystokinin (CCK) receptor-2 receptor antagonist YM022. Altogether, these data demonstrate that luminal leptin induces rapid inhibition of glucose entry into enterocyte. The slower action of leptin on the serosal side of mucosa seems indirect and is likely mediated by endogenous CCK. They demonstrate that gut leptin is a major regulator of rapid intestinal glucose transport.

  10. Treatment of fevers prior to introducing rapid diagnostic tests for malaria in registered drug shops in Uganda

    DEFF Research Database (Denmark)

    Mbonye, Anthony K.; Lal, Sham; Cundill, Bonnie

    2013-01-01

    shops on presenting symptoms, the consultation process, treatment received, and malaria diagnoses. Malaria diagnosis made by drug shop vendors were confirmed by the study team through microscopy examination of a blood slide to ascertain whether appropriate treatment was received. RESULTS: Among febrile......BACKGROUND: Since drug shops play an important role in treatment of fever, introducing rapid diagnostic tests (RDTs) for malaria at drug shops may have the potential of targeting anti-malarial drugs to those with malaria parasites and improve rational drug use. As part of a cluster randomized trial...... to examine impact on appropriate treatment of malaria in drug shops in Uganda and adherence to current malaria treatment policy guidelines, a survey was conducted to estimate baseline prevalence of, and factors associated with, appropriate treatment of malaria to enable effective design and implementation...

  11. Species differences in the dissolution and absorption of griseofulvin and albendazole, biopharmaceutics classification system class II drugs, in the gastrointestinal tract.

    Science.gov (United States)

    Tanaka, Yusuke; Waki, Ryoichi; Nagata, Shunji

    2013-01-01

    It is well known that large differences exist in the bioavailability of orally administered drugs between species. Dissolution is the first step in the oral absorption of solid drugs. In this study, we measured the in vivo luminal concentrations of griseofulvin (GF) and albendazole (AZ), Biopharmaceutics Classification System (BCS) class II drugs, and the GF fraction absorbed (Fa) in rats. Then, we compared the GF Fa in rat with that in other species reported previously to evaluate differences in drug dissolution and oral absorption. The Fa of GF has been reported to decrease from 80% to 40% with an increase in the oral dose in dogs and humans, because the rate-limiting step for absorption shifts from dissolution to solubility. However, such non-linearity was not observed in rats that were administered doses in the same ranges as those in humans, and the Fa values in rats were higher than those in dogs or humans. The in vivo luminal concentration of GF after oral administration in rats was much higher than the saturated solubility of GF in fasted-state simulated dog (FaSSIF(dog)) or human intestinal fluid (FaSSIF(human)). Furthermore, oral administration of AZ showed similar tendencies of interspecies differences in dissolution and oral absorption.

  12. Intestinal absorption of the antiepileptic drug substance vigabatrin in Göttingen mini-pigs is unaffected by co-administration of amino acids

    DEFF Research Database (Denmark)

    Nøhr, Martha Kampp; Holm, René; Thale, Zia Irene

    2014-01-01

    The anti-epileptic drug substance vigabatrin is used against infantile spasms. In vitro evidence suggests that vigabatrin is transported via the proton coupled amino acid transporter (PAT1). The aim of the present study was to investigate whether the intestinal absorption of vigabatrin in vivo wa...

  13. Evaluation of rapid alternative methods for drug susceptibility testing in clinical isolates of Mycobacterium tuberculosis

    Directory of Open Access Journals (Sweden)

    Luciano Mengatto

    2006-08-01

    Full Text Available A study was carried out to compare the performance of a commercial method (MGIT and four inexpensive drug susceptibility methods: nitrate reductase assay (NRA, microscopic observation drug susceptibility (MODS assay, MTT test, and broth microdilution method (BMM. A total of 64 clinical isolates of Mycobacterium tuberculosis were studied. The Lowenstein-Jensen proportion method (PM was used as gold standard. MGIT, NRA, MODS, and MTT results were available on an average of less than 10 days, whereas BMM results could be reported in about 20 days. Most of the evaluated tests showed excellent performance for isoniazid and rifampicin, with sensitivity and specificity values > 90%. With most of the assays, sensitivity for ethambutol was low (62-87% whereas for streptomycin, sensitivity values ranged from 84 to 100%; NRA-discrepancies were associated with cultures with a low proportion of EMB-resistant organisms while most discrepancies with quantitative tests (MMT and BMM were seen with isolates whose minimal inhibitory concentrations fell close the cutoff. MGIT is reliable but still expensive. NRA is the most inexpensive and easiest method to perform without changing the organization of the routine PM laboratory performance. While MODS, MTT, and BMM, have the disadvantage from the point of view of biosafety, they offer the possibility of detecting partial resistant strains. This study shows a very good level of agreement of the four low-cost methods compared to the PM for rapid detection of isoniazid, rifampicin and streptomycin resistance (Kappa values > 0.8; more standardization is needed for ethambutol.

  14. Veterinary drug residues in meat: Concerns and rapid methods for detection.

    Science.gov (United States)

    Reig, Milagro; Toldrá, Fidel

    2008-01-01

    The use of substances having hormonal or thyreostatic action as well as β-agonists is banned in the European Union. However, sometimes forbidden drugs may be added to feeds for illegal administration to farm animals for promoting increased muscle development or increased water retention and thus obtain an economical benefit. The result is a fraudulent overweight of meat but, what is worse, residues of these substances may remain in meat and may pose a real threat to the consumer either through exposure to the residues, transfer of antibiotic resistance or allergy risk. This has exerted a great concern among European consumers. The control of the absence of these forbidden substances in animal foods and feeds is regulated in the European Union by Directive96/23/EC on measures to monitor certain substances and residues in live animals and animal products. Analytical methodology, including criteria for identification and confirmation, for the monitoring of compliance was also given in Decisions 93/256/EEC and 93/257/EEC. More recently, Decision 2002/657/EC provided rules for the analytical methods to be used in testing of official samples. A crucial step is the screening of veterinary drug residues in live animals, feeds and animal products in view of the remarkable number of samples and large variety of residues to be analysed. In recent years, different rapid methods having easy performance, high sensitivity and high throughput have been proposed and are being extensively used. These methods as well as other new methods are reviewed in this manuscript.

  15. Curcumin-carboxymethyl chitosan (CNC) conjugate and CNC/LHR mixed polymeric micelles as new approaches to improve the oral absorption of P-gp substrate drugs.

    Science.gov (United States)

    Ni, Jiang; Tian, Fengchun; Dahmani, Fatima Zohra; Yang, Hui; Yue, Deren; He, Shuwang; Zhou, Jianping; Yao, Jing

    2016-11-01

    The low oral bioavailability of numerous drugs has been mostly attributed to the significant effect of P-gp-mediated efflux on intestinal drug transport. Herein, we developed mixed polymeric micelles (MPMs) comprised of curcumin-carboxymethyl chitosan (CNC) conjugate, as a potential inhibitor of P-gp-mediated efflux and gastrointestinal absorption enhancer, and low-molecular-weight heparin-all-trans-retinoid acid (LHR) conjugate, as loading material, with the aim to improve the oral absorption of P-gp substrate drugs. CNC conjugate was synthesized by chemical bonding of curcumin (Cur) and carboxymethyl chitosan (CMCS) taking advantage of the inhibition of intestinal P-gp-mediated secretion by Cur and the intestinal absorption enhancement by CMCS. The chemical structure of CNC conjugate was characterized by (1)H NMR with a degree of substitution of Cur of 4.52-10.20%. More importantly, CNC conjugate markedly improved the stability of Cur in physiological pH. Cyclosporine A-loaded CNC/LHR MPMs (CsA-CNC/LHR MPMs) were prepared by dialysis method, with high drug loading 25.45% and nanoscaled particle size (∼200 nm). In situ single-pass perfusion studies in rats showed that both CsA + CNC mixture and CsA-CNC/LHR MPMs achieved significantly higher Ka and Peff than CsA suspension in the duodenum and jejunum segments (p CNC mixture and CsA-CNC/LHR MPMs significantly increased the oral bioavailability of CsA as compared to CsA suspension. These results suggest that CNC conjugate might be considered as a promising gastrointestinal absorption enhancer, while CNC/LHR MPMs had the potential to improve the oral absorption of P-gp substrate drugs.

  16. Investigation of the effect of solubility increase at the main absorption site on bioavailability of BCS class II drug (risperidone) using liquisolid technique.

    Science.gov (United States)

    Khames, Ahmed

    2017-11-01

    BCS class II drugs usually suffer inadequate bioavailability as dissolution step is the absorption rate limiting step. In this work, the effect of solubility increase at the main absorption site for these drugs was investigated using risperidone as a drug model. Liquisolid technique was applied to prepare risperidone per-oral tablets of high dissolution rate at intestinal pH (6.8) using versatile nonionic surfactants of high solubilizing ability [Transcutol HP, Labrasol and Labrasol/Labrafil (1:1) mixture] as liquid vehicles at different drug concentrations (10-30%) and fixed (R). The prepared liquisolid tablets were fully evaluated and the dissolution rate at pH 6.8 was investigated. The formulae that showed significantly different release rate were selected and subjected to mathematical modeling using DE 25 , MDT and similarity factor (f2). Depending on mathematical modeling results, formula of higher dissolution rate was subjected to solid state characterization using differential scanning calorimetric (DSC), infrared spectroscopy (IR) and X-ray diffraction (XRD). Finally, the drug bioavailability was studied in comparison to conventional tablets in rabbits. Results showed that liquisolid tablet prepared using Labrasol/Labrafil (1:1) mixture as liquid vehicle containing 10% risperidone is a compatible formula with law drug crystallinity and higher dissolution rate (100% in 25 min). The drug bioavailability was significantly increased in comparison to the conventional tablets (1441.711 μg h/mL and 137.518 μg/mL in comparison to 321.011 μg h/mL and 38.673 μg/mL for AUC and Cp max , respectively). This led to the conclusion that liquisolid technique was efficiently improved drug solubility and solubility increase of BCS class II drugs at their main absorption site significantly increases their bioavailability.

  17. Acceptability of rapid oral fluid HIV testing among male injection drug users in Taiwan, 1997 and 2007.

    Science.gov (United States)

    Lyu, Shu-Yu; Morisky, Donald E; Yeh, Ching-Ying; Twu, Shiing-Jer; Peng, Eugene Yu-Chang; Malow, Robert M

    2011-04-01

    Rapid oral fluid HIV testing (rapid oral testing) is in the process of being adapted in Taiwan and elsewhere given its advantages over prior HIV testing methods. To guide this process, we examined the acceptability of rapid oral testing at two time points (i.e., 1997 and 2007) among one of the highest risk populations, male injection drug users (IDUs). For this purpose, an anonymous self-administered survey was completed by HIV-negative IDUs involved in the criminal justice system in 1997 (N (1)=137 parolees) and 2007 (N (2)=106 prisoners). A social marketing model helped guide the design of our questionnaire to assess the acceptability of rapid oral testing. This included assessing a new product, across four marketing dimensions: product, price, promotion, and place. Results revealed that in both 1997 and 2007, over 90% indicated that rapid oral testing would be highly acceptable, particularly if the cost was under US$6, and that a pharmacy would be the most appropriate and accessible venue for selling the rapid oral testing kits. The vast majority of survey respondents believed that the cost of rapid oral testing should be federally subsidized and that television and newspaper advertisements would be the most effective media to advertise for rapid oral testing. Both the 1997 and 2007 surveys suggested that rapid oral HIV testing would be particularly accepted in Taiwan by IDUs after release from the criminal justice system.

  18. Rapid detection of drug resistance and mutational patterns of extensively drug-resistant strains by a novel GenoType® MTBDRsl assay.

    Science.gov (United States)

    Singh, A K; Maurya, A K; Kant, S; Umrao, J; Kushwaha, R A S; Nag, V L; Dhole, T N

    2013-01-01

    The emergence of extensively drug-resistant tuberculosis (XDR-TB) is a major concern in the India. The burden of XDR-TB is increasing due to inadequate monitoring, lack of proper diagnosis, and treatment. The GenoType ® Mycobacterium tuberculosis drug resistance second line (MTBDRsl) assay is a novel line probe assay used for the rapid detection of mutational patterns conferring resistance to XDR-TB. The aim of this study was to study the rapid detection of drug resistance and mutational patterns of the XDR-TB by a novel GenoType ® MTBDRsl assay. We evaluated 98 multidrug-resistant (MDR) M. tuberculosis isolates for second line drugs susceptibility testing by 1% proportion method (BacT/ALERT 3D system) and GenoType ® MTBDRsl assay for rapid detection of conferring drug resistance to XDR-TB. A total of seven (17.4%) were identified as XDR-TB by using standard phenotypic method. The concordance between phenotypic and GenoType ® MTBDRsl assay was 91.7-100% for different antibiotics. The sensitivity and specificity of the MTBDRsl assay were 100% and 100% for aminoglycosides; 100% and 100% for fluoroquinolones; 91.7% and 100% for ethambutol. The most frequent mutations and patterns were gyrA MUT1 (A90V) in seven (41.2%) and gyrA + WT1-3 + MUT1 in four (23.5%); rrs MUT1 (A1401G) in 11 (64.7%), and rrs WT1-2 + MUT1 in eight (47.1%); and embB MUT1B (M306V) in 11 (64.7%) strains. These data suggest that the GenoType ® MTBDRsl assay is rapid, novel test for detection of resistance to second line anti-tubercular drugs. This assay provides additional information about the frequency and mutational patterns responsible for XDR-TB resistance.

  19. Polymer combination increased both physical stability and oral absorption of solid dispersions containing a low glass transition temperature drug: physicochemical characterization and in vivo study.

    Science.gov (United States)

    Sakurai, Atsushi; Sakai, Toshiro; Sako, Kazuhiro; Maitani, Yoshie

    2012-01-01

    The purpose of this study was establishing a solid dispersion formulation containing a low glass transition temperature (T(g)) and poorly water-soluble drug. Drug/polymer blends with differing physicochemical stabilities and oral absorption were prepared from copolyvidone (PVP-VA), polyvinylpyrrolidone (PVP) or hydroxypropylmethylcellulose (HPMC) by a hot melt extrusion. HPMC drastically increased the drug oral absorption property, while PVP-VA or PVP stabilized solid dispersions during storage by increasing the T(g) in proportion to polymer concentration. Experimental T(g) values corresponded closely with theoretical T(g) values; indeed, the T(g) values of solid dispersion with HPMC did not increase significantly compared to the T(g) value for the drug alone. A solid dispersion formulation incorporating two different polymers-HPMC and either PVP-VA or PVP-maintained increased T(g), physicochemical stability, solubility, and bioavailability of the solid dispresions owing to each polymer. These findings suggested that both oral absorption and physicochemical stability of low-T(g) drug will be improved using less amount of solid dispersion of combined two polymers than polymer alone.

  20. Loco-regional cancer drug therapy: present approaches and rapidly reversible hydrophobization (RRH) of therapeutic agents as the future direction.

    Science.gov (United States)

    Budker, Vladimir G; Monahan, Sean D; Subbotin, Vladimir M

    2014-12-01

    Insufficient drug uptake by solid tumors remains the major problem for systemic chemotherapy. Many studies have demonstrated anticancer drug effects to be dose-dependent, although dose-escalation studies have resulted in limited survival benefit with increased systemic toxicities. One solution to this has been the idea of loco-regional drug treatments, which offer dramatically higher drug concentrations in tumor tissues while minimizing systemic toxicity. Although loco-regional delivery has been most prominent in cancers of the liver, soft tissues and serosal peritoneal malignancies, survival benefits are very far from desirable. This review discusses the evolution of loco-regional treatments, the present approaches and offers rapidly reversible hydrophobization of drugs as the new future direction. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  1. Rapid assessment of drug use and sexual HIV risk patterns among ...

    African Journals Online (AJOL)

    This exploratory study examines the links between drug use and high-risk sexual practices and HIV in vulnerable drug-using populations in South Africa, including commercial sex workers (CSWs), men who have sex with men (MSM), injecting drug users (IDUs) and non-injecting drug users who are not CSWs or MSM ...

  2. Justification of Drug Product Dissolution Rate and Drug Substance Particle Size Specifications Based on Absorption PBPK Modeling for Lesinurad Immediate Release Tablets.

    Science.gov (United States)

    Pepin, Xavier J H; Flanagan, Talia R; Holt, David J; Eidelman, Anna; Treacy, Don; Rowlings, Colin E

    2016-09-06

    In silico absorption modeling has been performed, to assess the impact of in vitro dissolution on in vivo performance for ZURAMPIC (lesinurad) tablets. The dissolution profiles of lesinurad tablets generated using the quality control method were used as an input to a GastroPlus model to estimate in vivo dissolution in the various parts of the GI tract and predict human exposure. A model was set up, which accounts for differences of dosage form transit, dissolution, local pH in the GI tract, and fluid volumes available for dissolution. The predictive ability of the model was demonstrated by confirming that it can reproduce the Cmax observed for independent clinical trial. The model also indicated that drug product batches that pass the proposed dissolution specification of Q = 80% in 30 min are anticipated to be bioequivalent to the clinical reference batch. To further explore the dissolution space, additional simulations were performed using a theoretical dissolution profile below the proposed specification. The GastroPlus modeling indicates that such a batch will also be bioequivalent to standard clinical batches despite having a dissolution profile, which would fail the proposed dissolution specification of Q = 80% in 30 min. This demonstrates that the proposed dissolution specification sits comfortably within a region of dissolution performance where bioequivalence is anticipated and is not near an edge of failure for dissolution, providing additional confidence to the proposed specifications. Finally, simulations were performed using a virtual drug substance batch with a particle size distribution at the limit of the proposed specification for particle size. Based on these simulations, such a batch is also anticipated to be bioequivalent to clinical reference, demonstrating that the proposed specification limits for particle size distribution would give products bioequivalent to the pivotal clinical batches.

  3. Prediction of oral absorption of griseofulvin, a BCS class II drug, based on GITA model: utilization of a more suitable medium for in-vitro dissolution study.

    Science.gov (United States)

    Fujioka, Yoshitsugu; Kadono, Keitaro; Fujie, Yasuko; Metsugi, Yukiko; Ogawara, Ken-ichi; Higaki, Kazutaka; Kimura, Toshikiro

    2007-06-04

    The in-vivo absorbability of drugs categorized into the biopharmaceutics classification system (BCS) class II is very difficult to be predicted because of the large variability in the absorption and/or dissolution kinetics and the lack of an adequate in-vitro system for evaluating the dissolution behavior. We tried to predict the in-vivo absorption kinetics of griseofulvin, categorized into BCS class II, orally administrated as powders into rats, based on Gastrointestinal-Transit-Absorption model (GITA model), consisting of the absorption, dissolution and GI-transit processes. Using the dissolution rate constants (k(dis)) of griseofulvin obtained with JP 1st solution, JP 2nd solution, FaSSIF, FeSSIF and modified SIBLM as a medium, simulation lines were not able to describe the observed mean plasma profile at all. On the other hand, a calculated line provided by employing k(dis) obtained with MREVID 2 (medium reflecting in-vivo dissolution 2), a new medium, was in better agreement with the observed mean plasma profile than existing media, indicating that the utilization of adequate k(dis) value made it possible to predict the in-vivo absorption kinetics of drugs classified into BCS class II based on GITA model and that MREVID 2 could be a useful medium for describing the in-vivo dissolution kinetics.

  4. Rapid response of leaf photosynthesis in two fern species Pteridium aquilinum and Thelypteris dentata to changes in CO2 measured by tunable diode laser absorption spectroscopy.

    Science.gov (United States)

    Nishida, Keisuke; Kodama, Naomi; Yonemura, Seiichiro; Hanba, Yuko T

    2015-09-01

    We investigated stomatal conductance (g(s)) and mesophyll conductance (g(m)) in response to atmospheric CO2 concentration [CO2] in two primitive land plants, the fern species Pteridium aquilinum and Thelypteris dentata, using the concurrent measurement of leaf gas exchange and carbon isotope discrimination. [CO2] was initially decreased from 400 to 200 μmol mol(-1), and then increased from 200 to 700 μmol mol(-1), and finally decreased from 700 to 400 μmol mol(-1). Analysis by tunable diode laser absorption spectroscopy (TDLAS) revealed a rapid and continuous response in g m within a few minutes. In most cases, both ferns showed rapid and significant responses of g m to changes in [CO2]. The largest changes (quote % decrease) were obtained when [CO2] was decreased from 400 to 200 μmol mol(-1). This is in contrast to angiosperms where an increase in g(m) is commonly observed at low [CO2]. Similarly, fern species observed little or no response of g(s) to changes in [CO2] whereas, a concomitant decline of g(m) and g(s) with [CO2] is often reported in angiosperms. Together, these results suggest that regulation of g(m) to [CO2] may differ between angiosperms and ferns.

  5. The effect of rapid detoxification method with Naltrexone on drug abuse quitting in drug abusers referred to Khorramabad Psychiatric hospital during the first half of the year 2005

    Directory of Open Access Journals (Sweden)

    hedayat Nazari

    2009-03-01

    Full Text Available Background: About 8 percent of Iranian adult population are illicit drug abusers. Affected persons grow more each day. Ominous consequences such as divorce, prostitution, murder and other crimes and infectious diseases such as AIDS and hepatitis take place following drug abuse, as well as a loss equall to 29% of national income for our country. Traditional treatment methods wasted too much time and cost. professional inpatient clinics are not adequate for admission of all care seekers. Rapid detoxification methods are supposed to be better alternatives. Materials and Methods: 140 male drug abusers in two matched groups were assessed from March to September, 2005. They used heroin or opium. Both groups were scheduled for detoxification and were closely observed for 3 months thereafter. First group received Clonidine, Benzodiazepine and Naltrexone besides symptom relieving modalities in first 4 days of treatment. Naltrexone was continued in maintenance dose for one month. Second group received Methadone for one month. Results: Clients age was between 18 to 73 years, with mean age 34 years old. Their intelligence quotients were above the lower limit of normal range. There was no significant difference according to these parameters between two groups. Success rate in rapid detoxification group was 55 % and in Methadone group was 50 %. Relapse in rapid detoxification method occurred less frequent and slower (45 % vs. 50%. In Naltrexone group, better success rate was due to less duration of drug abuse and heroin dependency. In Methadone group, therapy had better results in patients with longer drug abuse history and opium addiction. There was no significant difference between success rate and either drug kind or job, marital status or education level. The most serious adverse effect in both groups was hypotension (10% in Naltrexone and 5 % in Methadone groups.

  6. DissolvIt: An In Vitro Method for Simulating the Dissolution and Absorption of Inhaled Dry Powder Drugs in the Lungs.

    Science.gov (United States)

    Gerde, Per; Malmlöf, Maria; Havsborn, Lina; Sjöberg, Carl-Olof; Ewing, Pär; Eirefelt, Stefan; Ekelund, Katarina

    The main purpose of this work was to develop an in vitro method for simulating the dissolution and absorption of inhaled dry powder drugs that also mimics systemic pharmacokinetic data. A second purpose was to evaluate this method. DissolvIt(®) was developed as a simulation of the air-blood barrier of the upper airways, constituting: "airborne" particles deposited on a glass cover slip, a mucus simulant, a polycarbonate (basal) membrane, and a pumped albumin buffer simulating the pulmonary blood flow. The PreciseInhale(®) exposure system was used to aerosolize and deposit test formulations onto cover slips. The particle dissolution was observed by optical microscopy as particle disappearance, and it was started directly when the particles came into contact with the mucus simulant. Solute from the dissolving particles diffused through the barrier and was absorbed into the perfusate. The drug concentration in the perfusate over time and the remaining drug in the barrier at the end of the experiment were quantitated by using liquid chromatography-tandem mass spectrometry. Budesonide and fluticasone propionate generated different pharmacokinetic dissolution/absorption profiles in DissolvIt. This study indicates that DissolvIt simulates dissolution and absorption of drugs in the lung, and that DissolvIt also mimics pharmacokinetic profiles and parameters.

  7. Comparative Genomic Analysis of Rapid Evolution of an Extreme-Drug-Resistant Acinetobacter baumannii Clone

    Science.gov (United States)

    Tan, Sean Yang-Yi; Chua, Song Lin; Liu, Yang; Høiby, Niels; Andersen, Leif Percival; Givskov, Michael; Song, Zhijun; Yang, Liang

    2013-01-01

    The emergence of extreme-drug-resistant (EDR) bacterial strains in hospital and nonhospital clinical settings is a big and growing public health threat. Understanding the antibiotic resistance mechanisms at the genomic levels can facilitate the development of next-generation agents. Here, comparative genomics has been employed to analyze the rapid evolution of an EDR Acinetobacter baumannii clone from the intensive care unit (ICU) of Rigshospitalet at Copenhagen. Two resistant A. baumannii strains, 48055 and 53264, were sequentially isolated from two individuals who had been admitted to ICU within a 1-month interval. Multilocus sequence typing indicates that these two isolates belonged to ST208. The A. baumannii 53264 strain gained colistin resistance compared with the 48055 strain and became an EDR strain. Genome sequencing indicates that A. baumannii 53264 and 48055 have almost identical genomes—61 single-nucleotide polymorphisms (SNPs) were found between them. The A. baumannii 53264 strain was assembled into 130 contigs, with a total length of 3,976,592 bp with 38.93% GC content. The A. baumannii 48055 strain was assembled into 135 contigs, with a total length of 4,049,562 bp with 39.00% GC content. Genome comparisons showed that this A. baumannii clone is classified as an International clone II strain and has 94% synteny with the A. baumannii ACICU strain. The ResFinder server identified a total of 14 antibiotic resistance genes in the A. baumannii clone. Proteomic analyses revealed that a putative porin protein was down-regulated when A. baumannii 53264 was exposed to antimicrobials, which may reduce the entry of antibiotics into the bacterial cell. PMID:23538992

  8. Rapid expansion of intravitreal drug injection procedures, 2000 to 2008: a population-based analysis.

    Science.gov (United States)

    Campbell, Robert J; Bronskill, Susan E; Bell, Chaim M; Paterson, J Michael; Whitehead, Marlo; Gill, Sudeep S

    2010-03-01

    To evaluate patterns of care for age-related macular degeneration following the introduction of vascular endothelial growth factor inhibitors. Using a population-based retrospective design, we studied monthly fee claims for intravitreal injections submitted to the Ontario Health Insurance Plan between January 1, 2000, and March 30, 2008, and linked procedures to the physicians who performed them. This database records physician services provided as part of universal health care insurance coverage in Ontario, Canada. This program covers all residents of Ontario, which had an average population of 12.1 million during the study period. Following regulatory approval of bevacizumab for colorectal cancer in 2005, off-label use of this drug for the treatment of retinal disease, particularly age-related macular degeneration, became increasingly common. The rate of intravitreal injections in Ontario rapidly grew 8-fold, and this growth preceded the availability of ranibizumab by more than a year. Moreover, in 2007, more than 50% of intravitreal injections in Ontario were performed by 3% of ophthalmologists. The development of vascular endothelial growth factor inhibitors has revolutionized the treatment of age-related macular degeneration. To our knowledge, this study is the first to quantify the dramatic uptake of these treatments at a population level. Our findings also suggest that off-label injection of bevacizumab was highly prevalent in Ontario. Serial intravitreal injections requiring direct physician administration and the concentration of injection procedures in the hands of a small number of ophthalmologists have the potential to affect services for other vision-threatening conditions.

  9. Protein tethering enables rapid and label-free SERS platform for screening drugs of abuse (Conference Presentation)

    Science.gov (United States)

    Siddhanta, Soumik; Wróbel, Maciej S.; Barman, Ishan

    2017-02-01

    A quick, cost-effective method for detection of drugs of abuse in biological fluids would be of great value in healthcare, law enforcement, and home testing applications. The alarming rise in narcotics abuse has led to considerable focus on developing potent and versatile analytical tools that can address this societal problem. While laboratory testing plays a key role in the current detection of drug misuse and the evaluation of patients with drug induced intoxication, these typically require expensive reagents and trained personnel, and may take hours to complete. Thus, a significant unmet need is to engineer a facile method that can rapidly detect drugs with little sample preparation, especially the bound fraction that is typically dominant in the blood stream. Here we report an approach that combines the exquisite sensitivity of surface enhanced Raman spectroscopy (SERS) and a facile protein tethering mechanism to reliably detect four different classes of drugs, barbiturate, benzodiazepine, amphetamine and benzoylecgonine. The proposed approach harnesses the reliable and specific attachment of proteins to both drugs and nanoparticle to facilitate the enhancement of spectral markers that are sensitive to the presence of the drugs. In conjunction with chemometric tools, we have shown the ability to quantify these drugs lower than levels achievable by existing clinical immunoassays. Through molecular docking simulations, we also probe the mechanistic underpinnings of the protein tethering approach, opening the door to detection of a broad class of narcotics in biological fluids within a few minutes as well as for groundwater analysis and toxin detection.

  10. Rapid antimicrobial susceptibility test for identification of new therapeutics and drug combinations against multidrug-resistant bacteria

    Science.gov (United States)

    Sun, Wei; Weingarten, Rebecca A; Xu, Miao; Southall, Noel; Dai, Sheng; Shinn, Paul; Sanderson, Philip E; Williamson, Peter R; Frank, Karen M; Zheng, Wei

    2016-01-01

    Current antimicrobial susceptibility testing has limited screening capability for identifying empirical antibiotic combinations to treat severe bacterial infections with multidrug-resistant (MDR) organisms. We developed a new antimicrobial susceptibility assay using automated ultra-high-throughput screen technology in combination with a simple bacterial growth assay. A rapid screening of 5170 approved drugs and other compounds identified 25 compounds with activities against MDR Klebsiella pneumoniae. To further improve the efficacy and reduce the effective drug concentrations, we applied a targeted drug combination approach that integrates drugs' clinical antimicrobial susceptibility breakpoints, achievable plasma concentrations, clinical toxicities and mechanisms of action to identify optimal drug combinations. Three sets of three-drug combinations were identified with broad-spectrum activities against 10 MDR clinical isolates including K. pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Citrobacter freundii, Enterobacter cloacae and Escherichia coli. Colistin–auranofin–ceftazidime and colistin–auranofin–rifabutin suppressed >80% growth of all 10 MDR strains; while rifabutin–colistin–imipenem inhibited >75% of these strains except two Acinetobacter baumannii isolates. The results demonstrate this new assay has potential as a real-time method to identify new drugs and effective drug combinations to combat severe clinical infections with MDR organisms. PMID:27826141

  11. Up-cycling waste glass to minimal water adsorption/absorption lightweight aggregate by rapid low temperature sintering: optimization by dual process-mixture response surface methodology.

    Science.gov (United States)

    Velis, Costas A; Franco-Salinas, Claudia; O'Sullivan, Catherine; Najorka, Jens; Boccaccini, Aldo R; Cheeseman, Christopher R

    2014-07-01

    Mixed color waste glass extracted from municipal solid waste is either not recycled, in which case it is an environmental and financial liability, or it is used in relatively low value applications such as normal weight aggregate. Here, we report on converting it into a novel glass-ceramic lightweight aggregate (LWA), potentially suitable for high added value applications in structural concrete (upcycling). The artificial LWA particles were formed by rapidly sintering (glass powder with clay mixes using sodium silicate as binder and borate salt as flux. Composition and processing were optimized using response surface methodology (RSM) modeling, and specifically (i) a combined process-mixture dual RSM, and (ii) multiobjective optimization functions. The optimization considered raw materials and energy costs. Mineralogical and physical transformations occur during sintering and a cellular vesicular glass-ceramic composite microstructure is formed, with strong correlations existing between bloating/shrinkage during sintering, density and water adsorption/absorption. The diametrical expansion could be effectively modeled via the RSM and controlled to meet a wide range of specifications; here we optimized for LWA structural concrete. The optimally designed LWA is sintered in comparatively low temperatures (825-835 °C), thus potentially saving costs and lowering emissions; it had exceptionally low water adsorption/absorption (6.1-7.2% w/wd; optimization target: 1.5-7.5% w/wd); while remaining substantially lightweight (density: 1.24-1.28 g.cm(-3); target: 0.9-1.3 g.cm(-3)). This is a considerable advancement for designing effective environmentally friendly lightweight concrete constructions, and boosting resource efficiency of waste glass flows.

  12. Evaluation of the use of Göttingen minipigs to predict food effects on the oral absorption of drugs in humans

    DEFF Research Database (Denmark)

    Christiansen, Martin Lau; Müllertz, Anette; Garmer, Mats

    2015-01-01

    This study investigated the oral absorption of drugs in minipigs to predict food effects in man. The protocol was based on a previously described model in dogs and further investigated the food source (i.e., US FDA breakfast or a nutritional drink) and food quantities. Two poorly soluble compounds...... in minipigs when compared with humans, within a range from 2.3 to 8.4 h dependent on the food regimen. There were no significant differences in drug absorption between fed and fasted state for the two compounds. The study showed that the dog protocol could not be transferred directly to minipigs, but needs...... were investigated [pravastatin (negative food effect) and atazanavir (positive food effect)] in Göttingen minipigs after seven different food regimens. The gastric emptying rate was evaluated by coadministration of acetaminophen. In short, the results demonstrated longer gastric emptying times...

  13. Rapid, automated, nonradiometric susceptibility testing of Mycobacterium tuberculosis complex to four first-line antituberculous drugs used in standard short-course chemotherapy

    DEFF Research Database (Denmark)

    Johansen, Isik Somuncu; Thomsen, Vibeke Østergaard; Marjamäki, Merja

    2004-01-01

    The increasing prevalence of drug-resistant tuberculosis necessitates rapid and accurate susceptibility testing. The nonradiometric BACTEC Mycobacteria Growth Indicator Tube 960 (MGIT) system for susceptibility testing was evaluated on 222 clinical Mycobacterium tuberculosis complex isolates...... MGIT system is a rapid and reliable alternative for susceptibility testing of M. tuberculosis complex to first-line drugs....

  14. Carboxylesterase 1A2 encoding gene with increased transcription and potential rapid drug metabolism in Asian populations

    DEFF Research Database (Denmark)

    Rasmussen, Henrik Berg; Madsen, Majbritt Busk; Lyauk, Yassine Kamal

    2017-01-01

    The carboxylesterase 1 gene (CES1) encodes a hydrolase implicated in the metabolism of commonly used drugs. CES1A2, a hybrid of CES1 and a CES1-like pseudogene, has a promoter that is weak in most individuals. However, some individuals harbor a promoter haplotype of this gene with two overlapping...... Sp1 sites that confer significantly increased transcription potentially leading to rapid drug metabolism. This CES1A2 haplotype has previously been reported to be common among Asians. Using polymerase chain reaction followed by sequencing, the present study examined variation in the promoter and 5...

  15. A rapid ex vivo tissue model for optimising drug detection and ionisation in MALDI imaging studies.

    Science.gov (United States)

    Huber, K; Aichler, M; Sun, N; Buck, A; Li, Z; Fernandez, I E; Hauck, S M; Zitzelsberger, H; Eickelberg, O; Janssen, K P; Keller, U; Walch, A

    2014-10-01

    The aim of this study was to establish an ex vivo model for a faster optimisation of sample preparation procedures, for example matrix choice, in matrix-assisted laser desorption/ionisation (MALDI) drug imaging studies. The ionisation properties of four drugs, afatinib, erlotinib, irinotecan and pirfenidone, were determined in an ex vivo tissue experiment by spotting decreasing dilution series onto liver sections. Hereby, the drug signals were distinctly detectable using different matrix compounds, which allowed the selection of the optimal matrix for each drug. The analysis of afatinib and erlotinib yielded high drug signals with α-cyano-4-hydroxycinnamic acid matrix, whereas 2,3-dihydroxybenzoic acid was identified as optimal matrix for irinotecan and pirfenidone detection. Our method was validated by a MALDI drug imaging approach of in vivo treated mouse tissue resulting in corresponding findings, indicating the spotting method as an appropriate approach to determine the matrix of choice. The present study shows the accordance between the detection of ex vivo spotted drugs and in vivo administered drugs by MALDI-TOF and MALDI-FT-ICR imaging, which has not been demonstrated so far. Our data suggest the ex vivo tissue spotting method as an easy and reliable model to optimise MALDI imaging measurements and to predict drug detection in tissue sections derived from treated mice prior to the recruitment of laboratory animals, which helps to save animals, time and costs.

  16. Rapid antimicrobial susceptibility test for identification of new therapeutics and drug combinations against multidrug-resistant bacteria

    OpenAIRE

    Sun, Wei; Weingarten, Rebecca A; Xu, Miao; Southall, Noel; Dai, Sheng; Shinn, Paul; Sanderson, Philip E; Williamson, Peter R; Frank, Karen M; Zheng, Wei

    2016-01-01

    Current antimicrobial susceptibility testing has limited screening capability for identifying empirical antibiotic combinations to treat severe bacterial infections with multidrug-resistant (MDR) organisms. We developed a new antimicrobial susceptibility assay using automated ultra-high-throughput screen technology in combination with a simple bacterial growth assay. A rapid screening of 5170 approved drugs and other compounds identified 25 compounds with activities against MDR Klebsiella pne...

  17. Rapid detection of drug resistance and mutational patterns of extensively drug-resistant strains by a novel GenoType® MTBDRsl assay

    Directory of Open Access Journals (Sweden)

    A K Singh

    2013-01-01

    Full Text Available Background: The emergence of extensively drug-resistant tuberculosis (XDR-TB is a major concern in the India. The burden of XDR-TB is increasing due to inadequate monitoring, lack of proper diagnosis, and treatment. The GenoType ® Mycobacterium tuberculosis drug resistance second line (MTBDRsl assay is a novel line probe assay used for the rapid detection of mutational patterns conferring resistance to XDR-TB. Aim: The aim of this study was to study the rapid detection of drug resistance and mutational patterns of the XDR-TB by a novel GenoType ® MTBDRsl assay. Materials and Methods: We evaluated 98 multidrug-resistant (MDR M. tuberculosis isolates for second line drugs susceptibility testing by 1% proportion method (BacT/ALERT 3D system and GenoType ® MTBDRsl assay for rapid detection of conferring drug resistance to XDR-TB. Results: A total of seven (17.4% were identified as XDR-TB by using standard phenotypic method. The concordance between phenotypic and GenoType ® MTBDRsl assay was 91.7-100% for different antibiotics. The sensitivity and specificity of the MTBDRsl assay were 100% and 100% for aminoglycosides; 100% and 100% for fluoroquinolones; 91.7% and 100% for ethambutol. The most frequent mutations and patterns were gyrA MUT1 (A90V in seven (41.2% and gyrA + WT1-3 + MUT1 in four (23.5%; rrs MUT1 (A1401G in 11 (64.7%, and rrs WT1-2 + MUT1 in eight (47.1%; and embB MUT1B (M306V in 11 (64.7% strains. Conclusions: These data suggest that the GenoType ® MTBDRsl assay is rapid, novel test for detection of resistance to second line anti-tubercular drugs. This assay provides additional information about the frequency and mutational patterns responsible for XDR-TB resistance.

  18. Flow analysis-hydride generation-gas phase derivative molecular absorption spectrophotometric determination of antimony in antileishmanial drugs

    Directory of Open Access Journals (Sweden)

    Máximo Gallignani

    2009-01-01

    Full Text Available In the present work, the development of a method based on the coupling of flow analysis (FA, hydride generation (HG, and derivative molecular absorption spectrophotometry (D-EAM in gas phase (GP, is described in order to determine total antimony in antileishmanial products. Second derivative order (D²224nm of the absorption spectrum (190 - 300 nm is utilized as measurement criterion. Each one of the parameters involved in the development of the proposed method was examined and optimized. The utilization of the EAM in GP as detection system in a continuous mode instead of atomic absorption spectrometry represents the great potential of the analytic proposal.

  19. The impact of supersaturation level for oral absorption of BCS class IIb drugs, dipyridamole and ketoconazole, using in vivo predictive dissolution system: Gastrointestinal Simulator (GIS).

    Science.gov (United States)

    Tsume, Yasuhiro; Matsui, Kazuki; Searls, Amanda L; Takeuchi, Susumu; Amidon, Gregory E; Sun, Duxin; Amidon, Gordon L

    2017-05-01

    The development of formulations and the assessment of oral drug absorption for Biopharmaceutical Classification System (BCS) class IIb drugs is often a difficult issue due to the potential for supersaturation and precipitation in the gastrointestinal (GI) tract. The physiological environment in the GI tract largely influences in vivo drug dissolution rates of those drugs. Thus, those physiological factors should be incorporated into the in vitro system to better assess in vivo performance of BCS class IIb drugs. In order to predict oral bioperformance, an in vitro dissolution system with multiple compartments incorporating physiologically relevant factors would be expected to more accurately predict in vivo phenomena than a one-compartment dissolution system like USP Apparatus 2 because, for example, the pH change occurring in the human GI tract can be better replicated in a multi-compartmental platform. The Gastrointestinal Simulator (GIS) consists of three compartments, the gastric, duodenal and jejunal chambers, and is a practical in vitro dissolution apparatus to predict in vivo dissolution for oral dosage forms. This system can demonstrate supersaturation and precipitation and, therefore, has the potential to predict in vivo bioperformance of oral dosage forms where this phenomenon may occur. In this report, in vitro studies were performed with dipyridamole and ketoconazole to evaluate the precipitation rates and the relationship between the supersaturation levels and oral absorption of BCS class II weak base drugs. To evaluate the impact of observed supersaturation levels on oral absorption, a study utilizing the GIS in combination with mouse intestinal infusion was conducted. Supersaturation levels observed in the GIS enhanced dipyridamole and ketoconazole absorption in mouse, and a good correlation between their supersaturation levels and their concentration in plasma was observed. The GIS, therefore, appears to represent in vivo dissolution phenomena and

  20. Rapid freeze-drying cycle optimization using computer programs developed based on heat and mass transfer models and facilitated by tunable diode laser absorption spectroscopy (TDLAS).

    Science.gov (United States)

    Kuu, Wei Y; Nail, Steven L

    2009-09-01

    Computer programs in FORTRAN were developed to rapidly determine the optimal shelf temperature, T(f), and chamber pressure, P(c), to achieve the shortest primary drying time. The constraint for the optimization is to ensure that the product temperature profile, T(b), is below the target temperature, T(target). Five percent mannitol was chosen as the model formulation. After obtaining the optimal sets of T(f) and P(c), each cycle was assigned with a cycle rank number in terms of the length of drying time. Further optimization was achieved by dividing the drying time into a series of ramping steps for T(f), in a cascading manner (termed the cascading T(f) cycle), to further shorten the cycle time. For the purpose of demonstrating the validity of the optimized T(f) and P(c), four cycles with different predicted lengths of drying time, along with the cascading T(f) cycle, were chosen for experimental cycle runs. Tunable diode laser absorption spectroscopy (TDLAS) was used to continuously measure the sublimation rate. As predicted, maximum product temperatures were controlled slightly below the target temperature of -25 degrees C, and the cascading T(f)-ramping cycle is the most efficient cycle design. In addition, the experimental cycle rank order closely matches with that determined by modeling.

  1. Rapid and simultaneous determination of essential minerals and trace elements in human milk by improved flame atomic absorption spectroscopy (FAAS) with microwave digestion.

    Science.gov (United States)

    Luo, Yang; Zhang, Bo; Chen, Ming; Wang, Jue; Zhang, Xue; Gao, Wei-Yin; Huang, Jun-Fu; Fu, Wei-Ling

    2010-09-08

    A method for the simultaneous and economical determination of many trace elements in human milk is developed. Two multi-element hollow cathode lamps (HCLs) were used instead of single-element HCLs to improve the sample throughput of flame atomic absorption spectroscopy (FAAS). The microwave digestion of milk is optimized prior to detection, and the performance characteristics of the improved analysis method are identified. Clinical samples are detected by both FAAS and inductively coupled plasma-optical emission spectroscopy (ICP-OES) for methodology evaluation. Results reveal that the proposed FAAS with multi-element HCLs could determine six essential minerals and trace elements within 15 min. This method provides a linear analytical range of 0.01-10 mg L(-1). For Ca, Cu, Fe, Mg, Mn, and Zn, the limits of determination are 1.5, 3, 1.8, 2.2, 2.1, and 1.3 microg L(-1), respectively. The mean relative standard deviations (RSDs) of intra- and interassays are lower than 7%. Excellent operational characteristics of rapidity, simplicity, and economy make the proposed method a promising one for the quantification of trace elements in human milk in clinics of underdeveloped areas.

  2. Rapid analysis of the interactions between drugs and human serum albumin (HSA) using high-performance affinity chromatography (HPAC).

    Science.gov (United States)

    Kim, Hee Seung; Wainer, Irving W

    2008-07-01

    This study used a combination of zonal elution and frontal affinity chromatography on immobilized human serum albumin (HSA) high-performance affinity chromatography (HPAC) column to examine the association constants of various compounds that have been studied by equilibrium dialysis or ultra filtration. A standard plot was generated from retention factors of reference compounds using zonal elution chromatography against association constants of reference compounds using frontal affinity chromatography. The linear relationship was established (r2=0.9993) between retention factors and association constants of reference compounds. This standard plot was later used for rapid determination of association constants of various drugs which show low to medium binding affinity to HSA. Association constants of those drugs from this study were compared to that of more generally used methods (i.e., equilibrium dialysis or ultra filtration) from literature and resulted in a relatively high correlation (r2=0.945) value. This combination of zonal elution and frontal affinity chromatography method for determining association constants showed several advantages against traditional methods. Depending on drugs of interest, an association constant of drug to HSA can be measured as fast as 1.5 min. Other notable advantages include an ease of automation and its ability to distinguish association constants of chiral compounds at the same time. The same approach could be used for studying interaction of other drugs and proteins and should further improve overall drug screening process.

  3. Rapid Detection and Identification of Overdose Drugs in Saliva by Surface-Enhanced Raman Scattering Using Fused Gold Colloids

    Directory of Open Access Journals (Sweden)

    Frank Inscore

    2011-07-01

    Full Text Available The number of drug-related emergency room visits in the United States doubled from 2004 to 2009 to 4.6 million. Consequently there is a critical need to rapidly identify the offending drug(s, so that the appropriate medical care can be administered. In an effort to meet this need we have been investigating the ability of surface-enhanced Raman spectroscopy (SERS to detect and identify numerous drugs in saliva at ng/mL concentrations within 10 minutes. Identification is provided by matching measured spectra to a SERS library comprised of over 150 different drugs, each of which possess a unique spectrum. Trace detection is provided by fused gold colloids trapped within a porous glass matrix that generate SERS. Speed is provided by a syringe-driven sample system that uses a solid-phase extraction capillary combined with a SERS-active capillary in series. Spectral collection is provided by a portable Raman analyzer. Here we describe successful measurement of representative illicit, prescribed, and over-the-counter drugs by SERS, and 50 ng/mL cocaine in saliva as part of a focused study.

  4. Intestinal absorption of the antiepileptic drug substance vigabatrin is altered by infant formula in vitro and in vivo

    DEFF Research Database (Denmark)

    Nielsen, Carsten Uhd

    2014-01-01

    in Caco-2 cells. Oral coadministration of vigabatrin and infant formula significantly reduced Cmax and prolonged tmax of vigabatrin absorption. Ligands for the proton-coupled amino acid transporter PAT1, sarcosine, and proline/l-tryptophan had similar effects on the pharmacokinetic profile of vigabatrin....... The infant formula decreased the rate of gastric emptying. Here we provide experimental evidence for an in vivo role of PAT1 in the intestinal absorption of vigabatrin. The effect of infant formula on the oral absorption of vigabatrin was found to be due to delayed gastric emptying, however, it seems...... reasonable that infant formula may also directly affect the intestinal absorption rate of vigabatrin possibly via PAT1....

  5. Adenovirus-vectored drug-vaccine duo as a rapid-response tool for conferring seamless protection against influenza.

    Directory of Open Access Journals (Sweden)

    Jianfeng Zhang

    Full Text Available Few other diseases exert such a huge toll of suffering as influenza. We report here that intranasal (i.n. administration of E1/E3-defective (ΔE1E3 adenovirus serotype 5 (Ad5 particles rapidly induced an anti-influenza state as a means of prophylactic therapy which persisted for several weeks in mice. By encoding an influenza virus (IFV hemagglutinin (HA HA1 domain, an Ad5-HA1 vector conferred rapid protection as a prophylactic drug followed by elicitation of sustained protective immunity as a vaccine for inducing seamless protection against influenza as a drug-vaccine duo (DVD in a single package. Since Ad5 particles induce a complex web of host responses, which could arrest influenza by activating a specific arm of innate immunity to impede IFV growth in the airway, it is conceivable that this multi-pronged influenza DVD may escape the fate of drug resistance that impairs the current influenza drugs.

  6. Embryonic Zebrafish Model - A Well-Established Method for Rapidly Assessing the Toxicity of Homeopathic Drugs - Toxicity Evaluation of Homeopathic Drugs Using Zebrafish Embryo Model -

    Directory of Open Access Journals (Sweden)

    Himanshu R Gupta

    2016-12-01

    exposure times used in this study. The embryonic zebrafish model is recommended as a well-established method for rapidly assessing the toxicity of homeopathic drugs.

  7. Rapid identification of drug-type strains in Cannabis sativa using loop-mediated isothermal amplification assay.

    Science.gov (United States)

    Kitamura, Masashi; Aragane, Masako; Nakamura, Kou; Watanabe, Kazuhito; Sasaki, Yohei

    2017-01-01

    In Cannabis sativa L., tetrahydrocannabinol (THC) is the primary psychoactive compound and exists as the carboxylated form, tetrahydrocannabinolic acid (THCA). C. sativa is divided into two strains based on THCA content-THCA-rich (drug-type) strains and THCA-poor (fiber-type) strains. Both strains are prohibited by law in many countries including Japan, whereas the drug-type strains are regulated in Canada and some European countries. As the two strains cannot be discriminated by morphological analysis, a simple method for identifying the drug-type strains is required for quality control in legal cultivation and forensic investigation. We have developed a novel loop-mediated isothermal amplification (LAMP) assay for identifying the drug-type strains of C. sativa. We designed two selective LAMP primer sets for on-site or laboratory use, which target the drug-type THCA synthase gene. The LAMP assay was accomplished within approximately 40 min. The assay showed high specificity for the drug-type strains and its sensitivity was the same as or higher than that of conventional polymerase chain reaction. We also showed the effectiveness of melting curve analysis that was conducted after the LAMP assay. The melting temperature values of the drug-type strains corresponded to those of the cloned drug-type THCA synthase gene, and were clearly different from those of the cloned fiber-type THCA synthase gene. Moreover, the LAMP assay with simple sample preparation could be accomplished within 1 h from sample treatment to identification without the need for special devices or techniques. Our rapid, sensitive, specific, and simple assay is expected to be applicable to laboratory and on-site detection.

  8. Introducing rapid diagnostic tests for malaria into registered drug shops in Uganda: lessons learned and policy implications.

    Science.gov (United States)

    Mbonye, Anthony K; Clarke, Sîan E; Lal, Sham; Chandler, Clare I; Hutchinson, Eleanor; Hansen, Kristian S; Magnussen, Pascal

    2015-11-14

    Malaria is a major public health problem in Uganda and the current policy recommends introduction of rapid diagnostic tests for malaria (RDTs) to facilitate effective case management. However, provision of RDTs in drug shops potentially raises a new set of issues, such as adherence to RDTs results, management of severe illnesses, referral of patients, and relationship with caretakers. The main objective of the study was to examine the impact of introducing RDTs in registered drug shops in Uganda and document lessons and policy implications for future scale-up of malaria control in the private health sector. A cluster-randomized trial introducing RDTs into registered drug shops was implemented in central Uganda from October 2010 to July 2012. An evaluation was undertaken to assess the impact and the processes involved with the introduction of RDTs into drug shops, the lessons learned and policy implications. Introducing RDTs into drug shops was feasible. To scale-up this intervention however, drug shop practices need to be regulated since the registration process was not clear, supervision was inadequate and record keeping was poor. Although initially it was anticipated that introducing a new practice of record keeping would be cumbersome, but at evaluation this was not found to be a constraint. This presents an important lesson for introducing health management information system into drug shops. Involving stakeholders, especially the district health team, in the design was important for ownership and sustainability. The involvement of village health teams in community sensitization to the new malaria treatment and diagnosis policy was a success and this strategy is recommended for future interventions. Introducing RDTs into drug shops was feasible and it increased appropriate treatment of malaria with artemisinin-based combination therapy. It is anticipated that the lessons presented will help better implementation of similar interventions in the private sector.

  9. Application of lean manufacturing concepts to drug discovery: rapid analogue library synthesis.

    Science.gov (United States)

    Weller, Harold N; Nirschl, David S; Petrillo, Edward W; Poss, Michael A; Andres, Charles J; Cavallaro, Cullen L; Echols, Martin M; Grant-Young, Katherine A; Houston, John G; Miller, Arthur V; Swann, R Thomas

    2006-01-01

    The application of parallel synthesis to lead optimization programs in drug discovery has been an ongoing challenge since the first reports of library synthesis. A number of approaches to the application of parallel array synthesis to lead optimization have been attempted over the years, ranging from widespread deployment by (and support of) individual medicinal chemists to centralization as a service by an expert core team. This manuscript describes our experience with the latter approach, which was undertaken as part of a larger initiative to optimize drug discovery. In particular, we highlight how concepts taken from the manufacturing sector can be applied to drug discovery and parallel synthesis to improve the timeliness and thus the impact of arrays on drug discovery.

  10. Drug-Related Hyponatremic Encephalopathy: Rapid Clinical Response Averts Life-Threatening Acute Cerebral Edema

    OpenAIRE

    Siegel, Arthur J; Forte, Sophie S.; Bhatti, Nasir A.; Gelda, Steven E.

    2016-01-01

    Patient: Female, 63 Final Diagnosis: Drug-induced hyponatremic encephalopathy Symptoms: Seizures ? coma Medication: Hypertonic 3% saline infusion Clinical Procedure: ? Specialty: Internal Medicine Objective: Unusual clinical course Background: Drug-induced hyponatremia characteristically presents with subtle psychomotor symptoms due to its slow onset, which permits compensatory volume adjustment to hypo-osmolality in the central nervous system. Due mainly to the syndrome of inappropriate anti...

  11. Studies on effective atomic numbers for photon energy absorption and electron density of some narcotic drugs in the energy range 1 keV-20 MeV

    Science.gov (United States)

    Gounhalli, Shivraj G.; Shantappa, Anil; Hanagodimath, S. M.

    2013-04-01

    Effective atomic numbers for photon energy absorption ZPEA,eff, photon interaction ZPI,eff and for electron density Nel, have been calculated by a direct method in the photon-energy region from 1 keV to 20 MeV for narcotic drugs, such as Heroin (H), Cocaine (CO), Caffeine (CA), Tetrahydrocannabinol (THC), Cannabinol (CBD), Tetrahydrocannabivarin (THCV). The ZPEA,eff, ZPI,eff and Nel values have been found to change with energy and composition of the narcotic drugs. The energy dependence ZPEA,eff, ZPI,eff and Nel is shown graphically. The maximum difference between the values of ZPEA,eff, and ZPI,eff occurs at 30 keV and the significant difference of 2 to 33% for the energy region 5-100 keV for all drugs. The reason for these differences is discussed.

  12. Surface-stress sensors for rapid and ultrasensitive detection of active free drugs in human serum

    Science.gov (United States)

    Ndieyira, Joseph W.; Kappeler, Natascha; Logan, Stephen; Cooper, Matthew A.; Abell, Chris; McKendry, Rachel A.; Aeppli, Gabriel

    2014-03-01

    There is a growing appreciation that mechanical signals can be as important as chemical and electrical signals in biology. To include such signals in a systems biology description for understanding pathobiology and developing therapies, quantitative experiments on how solution-phase and surface chemistry together produce biologically relevant mechanical signals are needed. Because of the appearance of drug-resistant hospital `superbugs', there is currently great interest in the destruction of bacteria by bound drug-target complexes that stress bacterial cell membranes. Here, we use nanomechanical cantilevers as surface-stress sensors, together with equilibrium theory, to describe quantitatively the mechanical response of a surface receptor to different antibiotics in the presence of competing ligands in solution. The antibiotics examined are the standard, Food and Drug Administration-approved drug of last resort, vancomycin, and the yet-to-be approved oritavancin, which shows promise for controlling vancomycin-resistant infections. The work reveals variations among strong and weak competing ligands, such as proteins in human serum, that determine dosages in drug therapies. The findings further enhance our understanding of the biophysical mode of action of the antibiotics and will help develop better treatments, including choice of drugs as well as dosages, against pathogens.

  13. Absorption-desorption of drugs in porous polymers obtained by plasma; Absorcion-desorcion de farmacos en polimeros porosos obtenidos por plasma

    Energy Technology Data Exchange (ETDEWEB)

    Gonzalez T, M.

    2016-07-01

    A study about drug absorption and release in plasma polymers is presented in this work, these materials can be used as implants in the human body. In these applications the polymer should be biocompatible and/or biodegradable. Poly pyrroles and poly allylamine s synthesized by plasma have amine groups in their structure which makes them biocompatible with potential as drug carriers. In this function, the polymers were lyophilized to induce pores where the drug can be hosted. Drug-polymer mixtures with 1:10 ratio were prepared. The mixture morphology was studied by Scanning Electron Microscopy while their chemical structure was studied by Infrared Spectroscopy and X-ray Photoelectron Spectroscopy. Two models were studied to assess drug release, dynamic and static, in two solutions: water and Krebs Ringer (Kr) using the UV characteristic absorbance of each drug. In the static model release, 5 mg of the mixture were placed in 10 ml of solution. In the dynamic model, the release was performed with 5 mg of the mixture in 10 ml of solution, 1.5 ml of release medium was removed for UV analysis and replaced with an equal volume of fresh medium. The results indicate that the morphology of the polymers was modified with the lyophilization, in Poly pyrrole pores were induced with diameter in the range of 0.7 to 19 μm, while in Polyallyl amine the surface changed from smooth to rough. Drugs were absorbed in Poly pyrrole by filling the pores first and then coating the polymer with a drug layer. In Poly allylamine the drugs adhered to the polymer surface. Analyzing the atomic orbitals of the mixtures, it was found that the drugs interacted with the polymer. The most affected orbital was S2p, whose separation between 1/2 and 3/2 sub orbitals increased from 0.9 eV in Dapsone and Heparin to 4 eV in the mixtures, where the oxidation state changed from valence 6 to 6 and 2 in the mixtures. This suggests physicochemical interaction between drug and polymer. The drugs were released

  14. Delayed absorption of many (paracetamol, aspirin, other NSAIDs and zolmitriptan) but not all (sumatriptan, rizatriptan) drugs during migraine attacks and most likely normal gastric emptying outside attacks. A review

    DEFF Research Database (Denmark)

    Tfelt-Hansen, Peer Carsten

    2017-01-01

    . Results In seven studies, mainly investigating NSAIDs and analgesics, the early absorption of the drugs during 112 migraine attacks was delayed. The absorption of sumatriptan is usual in therapeutic doses, and rizatriptan was normal during 131 migraine attacks. The interictal gastric stasis observed using...

  15. A high throughput solubility assay for drug discovery using microscale shake-flask and rapid UHPLC-UV-CLND quantification.

    Science.gov (United States)

    Lin, Baiwei; Pease, Joseph H

    2016-04-15

    The rapid determination of key physical properties of lead compounds is essential to the drug discovery process. Solubility is one of the most important properties since good solubility is needed not only for obtaining reliable in vitro and in vivo assay results in early discovery but also to ensure sufficient concentration of the drug being in circulation to get the desired therapeutic exposure at the target of interest. In order for medicinal chemists to tune solubility of lead compounds, a rapid assay is needed to provide solubility data that is accurate and predictive so that it can be reliably used for designing the next generation of compounds with improved properties. To ensure speed and data quality, we developed a high throughput solubility assay that utilizes a single calibration UHPLC-UV-CLND method and a 24h shake-flask format for rapid quantification. A set of 46 model compounds was used to demonstrate that the method is accurate, reproducible and predictive. Here we present development of the assay, including evaluation of quantification method, filtration membranes, equilibrium times, DMSO concentrations, and buffer conditions. A comparison of thermodynamic solubility results to our high throughput 24h shake-flask solubility assay results is also discussed. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. sup 51 Cr-ethylenediaminetetraacetic acid absorption test; Effects of naproxen, a non-steroidal antiinflammatory drug

    Energy Technology Data Exchange (ETDEWEB)

    Aabakken, L.; Osnes, M. (Ullevaal Sykehus, Oslo (Norway))

    1990-01-01

    Eighty volunteers were studied to determine the effects of 750 or 1000 mg naproxen daily for a week on intestinal permeability, by means of the {sup 51}Cr-ethylenediaminetetraacetic acid (EDTA) absorption test. With 750 mg naproxen the median urinary excretion increased from 2.44% to 3.51%, and with 1000 mg from 2.26% to 3.39%. When the individual pretreatment absorption was included in the analysis, a statistically significant difference was found between the two doses. Similar results were found in 27 subjects who were given both doses of naproxen. Intraduodenal instillation of the test dose in 18 subjects showed that gastric absorption was negligible, and no correlation was found with upper endoscopy findings, changes in orocoecal transit time, or reported symptoms. 25 refs., 3 figs., 3 tabs.

  17. Prospective multicentre evaluation of the direct nitrate reductase assay for the rapid detection of extensively drug-resistant tuberculosis.

    Science.gov (United States)

    Martin, Anandi; Imperiale, Belen; Ravolonandriana, Pascaline; Coban, Ahmet Yilmaz; Akgunes, Alper; Ikram, Aamer; Satti, Luqman; Odoun, Mathieu; Pandey, Pooja; Mishra, Manvi; Affolabi, Dissou; Singh, Urvashi; Rasolofo, Voahangy; Morcillo, Nora; Vandamme, Peter; Palomino, Juan Carlos

    2014-02-01

    To perform a multicentre study evaluating the performance of the direct nitrate reductase assay (NRA) for the detection of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis in sputum samples. The study was conducted in six laboratories performing tuberculosis diagnosis that were located in six different countries. The NRA was performed directly on sputum samples in parallel with the reference method used at each site. Detection of resistance was performed for rifampicin, isoniazid, ofloxacin and kanamycin. Excellent agreement was obtained for all drugs tested at the majority of sites. The accuracy was 93.7%-100% for rifampicin, 88.2%-100% for isoniazid, 94.6%-100% for ofloxacin and 100% for kanamycin. The majority of NRA results were available at day 21 for sites 1, 2 and 5. Site 3 had a turnaround time of 13.9 days, at site 4 it was 18.4 days and at site 6 it was 16.2 days. The contamination rate ranged between 2.5% and 12%. Rapid detection of drug resistance by the direct NRA on sputum smear-positive samples was accurate and easy to implement in clinical diagnostic laboratories, making it a good alternative for rapid screening for MDR and XDR tuberculosis.

  18. Comparative Genomic Analysis of Rapid Evolution of an Extreme-Drug-Resistant Acinetobacter baumannii Clone

    DEFF Research Database (Denmark)

    Tan, Sean Yang-Yi; Chua, Song Lin; Liu, Yang

    2013-01-01

    , comparative genomics has been employed to analyze the rapid evolution of an EDR Acinetobacter baumannii clone from the intensive care unit (ICU) of Rigshospitalet at Copenhagen. Two resistant A. baumannii strains, 48055 and 53264, were sequentially isolated from two individuals who had been admitted to ICU...

  19. A heuristic model to quantify the impact of excess cyclodextrin on oral drug absorption from aqueous solution

    DEFF Research Database (Denmark)

    Olesen, Niels Erik; Westh, Peter; Holm, René

    2016-01-01

    The intestinal drug solubilising capacity View the MathML source(DtotSC) of a drug formulated as an aqueous cyclodextrin solution is a recently proposed quantity to predict the cyclodextrin concentration needed to fully solubilise the drug in the intestinal lumen. According to this concept......, the cyclodextrin concentration in the drug product must be higher than the amount needed to solubilise the compound, due to the displacement of the drug from the cyclodextrin cavity by bile salts in the intestinal lumen. On the other hand, dosing cyclodextrin at View the MathML source>DtotSC is expected to result...... in decreased free intestinal drug concentrations and thus potentially a lower fraction absorbed. In this study, data from three previous in vivo studies in rats with fixed concentrations of three compounds (danazol, cinnarizine and benzo[A]pyrene) and various cyclodextrin concentrations View the MathML source...

  20. Drug quantification in turbid media by fluorescence imaging combined with light-absorption correction using white Monte Carlo simulations

    DEFF Research Database (Denmark)

    Xie, Haiyan; Liu, Haichun; Svenmarker, Pontus

    2011-01-01

    Accurate quantification of photosensitizers is in many cases a critical issue in photodynamic therapy. As a noninvasive and sensitive tool, fluorescence imaging has attracted particular interest for quantification in pre-clinical research. However, due to the absorption of excitation and emission...

  1. Ionic Liquid Forms of Weakly Acidic Drugs in Oral Lipid Formulations: Preparation, Characterization, in Vitro Digestion, and in Vivo Absorption Studies.

    Science.gov (United States)

    Sahbaz, Yasemin; Nguyen, Tri-Hung; Ford, Leigh; McEvoy, Claire L; Williams, Hywel D; Scammells, Peter J; Porter, Christopher J H

    2017-11-06

    This study aimed to transform weakly acidic poorly water-soluble drugs (PWSD) into ionic liquids (ILs) to promote solubility in, and the utility of, lipid-based formulations. Ionic liquids (ILs) were formed directly from tolfenamic acid (Tolf), meclofenamic acid, diclofenac, and ibuprofen by pairing with lipophilic counterions. The drug-ILs were obtained as liquids or low melting solids and were significantly more soluble (either completely miscible or highly soluble) in lipid based, self-emulsifying drug delivery systems (SEDDS) when compared to the equivalent free acid. In vivo assessment of a SEDDS lipid solution formulation of Tolf didecyldimethylammonium salt and the same formulation of Tolf free acid at low dose (18 mg/kg, where the free acid was soluble in the SEDDS), resulted in similar absorption profiles and overall exposure. At high dose (100 mg/kg), solution SEDDS formulations of the Tolf ILs (didecyldimethylammonium, butyldodecyldimethylammonium or didecylmethylammonium salts) were possible, but the lower lipid solubility of Tolf free acid dictated that administration of the free acid was only possible as a suspension in the SEDDS formulation or as an aqueous suspension. Under these conditions, total drug plasma exposure was similar for the IL formulations and the free acid, but the plasma profiles were markedly different, resulting in flatter, more prolonged exposure profiles and reduced Cmax for the IL formulations. Isolation of a weakly acidic drug as an IL may therefore provide advantage as it allows formulation as a solution SEDDS rather than a lipid suspension, and in some cases may provide a means of slowing or sustaining absorption. The current studies compliment previous studies with weakly basic PWSD and demonstrate that transformation into highly lipophilic ILs is also possible for weakly acidic compounds.

  2. Rhabdomyolysis in MDMA intoxication : A rapid and underestimated killer. "clean" Ecstasy, a safe party drug?

    NARCIS (Netherlands)

    Eede, Herve Vanden; Montenij, Leon J.; Touw, Daan J.; Norris, Elizabeth M.

    Background: Ecstasy is a popular drug among young adults. It is often thought to be safe. The dose of methylenedioxymethamphetamine (MDMA) in a tablet of Ecstasy varies greatly, and there is also a difference in individual response to a dose of MDMA. Objectives: To increase the awareness of

  3. Direct nitrate reductase assay versus microscopic observation drug susceptibility test for rapid detection of MDR-TB in Uganda.

    Directory of Open Access Journals (Sweden)

    Freddie Bwanga

    Full Text Available The most common method for detection of drug resistant (DR TB in resource-limited settings (RLSs is indirect susceptibility testing on Lowenstein-Jensen medium (LJ which is very time consuming with results available only after 2-3 months. Effective therapy of DR TB is therefore markedly delayed and patients can transmit resistant strains. Rapid and accurate tests suitable for RLSs in the diagnosis of DR TB are thus highly needed. In this study we compared two direct techniques--Nitrate Reductase Assay (NRA and Microscopic Observation Drug Susceptibility (MODS for rapid detection of MDR-TB in a high burden RLS. The sensitivity, specificity, and proportion of interpretable results were studied. Smear positive sputum was collected from 245 consecutive re-treatment TB patients attending a TB clinic in Kampala, Uganda. Samples were processed at the national reference laboratory and tested for susceptibility to rifampicin and isoniazid with direct NRA, direct MODS and the indirect LJ proportion method as reference. A total of 229 specimens were confirmed as M. tuberculosis, of these interpretable results were obtained in 217 (95% with either the NRA or MODS. Sensitivity, specificity and kappa agreement for MDR-TB diagnosis was 97%, 98% and 0.93 with the NRA; and 87%, 95% and 0.78 with the MODS, respectively. The median time to results was 10, 7 and 64 days with NRA, MODS and the reference technique, respectively. The cost of laboratory supplies per sample was low, around 5 USD, for the rapid tests. The direct NRA and MODS offered rapid detection of resistance almost eight weeks earlier than with the reference method. In the study settings, the direct NRA was highly sensitive and specific. We consider it to have a strong potential for timely detection of MDR-TB in RLS.

  4. Discrimination and quantification of two isomeric antineoplastic drugs by rapid and non-invasive analytical control using a handheld Raman spectrometer.

    Science.gov (United States)

    Lê, L M M; Tfayli, A; Zhou, J; Prognon, P; Baillet-Guffroy, A; Caudron, E

    2016-12-01

    Raman spectroscopy is a rapid, non-destructive and non-invasive method that is a promising tool for real-time analytical control of drug concentrations. This study evaluated a handheld Raman device to discriminate and quantify two isomeric drugs used to treat cancer. Doxorubicin (DOXO) and epirubicin (EPIR) samples were analyzed at therapeutic concentrations from 0.1 to 2mg/mL (n=90) and 0.08-2mg/mL (n=90) by non-invasive measurements using a portable Raman spectrometer. The discrimination of these two molecules was demonstrated for all concentrations (n=180) by qualitative analysis using partial least square discriminant analysis (PLS-DA) with 100% classification accuracy, sensitivity and specificity and 0% error rate. For each molecule, quantitative analyses were performed using PLS regression. The validity of the model was evaluated using root mean square error of cross validation (RMSECV) and prediction (RMSEP) that furnished 0.05 and 0.02mg/mL for DOXO and 0.17 and 0.16mg/mL for EPIR after pretreatment optimization. Based on the accuracy profile, the linearity range was from 1.256 to 2.000mg/mL for DOXO (R2=0.9988) and from 0.553 to 2.000mg/Ml for EPIR (R2=0.9240) and repeatability (CV% max of 1.8% for DOXO and 3.2% for EPIR) and intermediate precision (CV% max of 2.8% for DOXO and 4.5% for EPIR) were both acceptable. Despite the narrow validated concentration range for quantitative analysis, this study shows the potential of a handheld Raman spectrometer coupled to chemometric approaches for real-time quantification of cytotoxic drugs, as well for discriminating between two drugs with similar UV absorption profiles. Finally, the use of a handheld spectrometer with the possibility of a direct measurement of substances in containers is a potentially valuable tool for combining patient safety with security of healthcare workers. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Assessment of veterinary drugs in plants using pharmacokinetic approaches: The absorption, distribution and elimination of tetracycline and sulfamethoxazole in ephemeral vegetables.

    Directory of Open Access Journals (Sweden)

    Hui-Ru Chen

    Full Text Available The present study was carried out to demonstrate novel use of pharmacokinetic approaches to characterize drug behaviors/movements in the vegetables with implications to food safety. The absorption, distribution, metabolism and most importantly, the elimination of tetracycline (TC and sulfamethoxazole (SMX in edible plants Brassica rapa chinensis and Ipomoea aquatica grown hydroponically were demonstrated and studied using non-compartmental pharmacokinetic analysis. The results revealed drug-dependent and vegetable-dependent pharmacokinetic differences and indicated that ephemeral vegetables could have high capacity accumulating antibiotics (up to 160 μg g-1 for TC and 38 μg g-1 for SMX within hours. TC concentration in the root (Cmax could reach 11 times higher than that in the cultivation fluid and 3-28 times higher than the petioles/stems. Based on the volume of distribution (Vss, SMX was 3-6 times more extensively distributed than TC. Both antibiotics showed evident, albeit slow elimination phase with elimination half-lives ranging from 22 to 88 hours. For the first time drug elimination through the roots of a plant was demonstrated, and by viewing the root as a central compartment and continuous infusion without a loading dose as drug administration mode, it is possible to pharmacokinetically monitor the movement of antibiotics and their fate in the vegetables with more detailed information not previously available. Phyto-pharmacokinetic could be a new area worth developing new models for the assessment of veterinary drugs in edible plants.

  6. Evaluation of GenoType® MTBDRplus assay for rapid detection of drug susceptibility testing of multi-drug resistance tuberculosis in Northern India.

    Science.gov (United States)

    Maurya, Anand Kumar; Umrao, Jyoti; Singh, Amresh Kumar; Kant, Surya; Kushwaha, Ram Awadh Singh; Dhole, Tapan N

    2013-01-01

    The problem of multi-drug resistance tuberculosis (MDR-TB) is growing in several hotspots throughout the world. Rapid and accurate diagnosis of MDR-TB is crucial to facilitate early treatment and to reduce its spread in the community. The aim of the present study was to evaluate the new, novel GenoType® MTBDRplus assay for rapid detection of drug susceptibility testing (DST) of MDR-TB cases in Northern India. A total of 550 specimens were collected from highly suspected drug resistant from pulmonary and extra-pulmonary TB cases. All the specimens were processed by Ziehl- Neelsen staining, culture, differentiation by the GenoType® CM assay, first line DST using BacT/ALERT 3D system and GenoType® MTBDRplus assay. The concordance of the GenoType® MTBDRplus assay was calculated in comparison with conventional DST results. Overall the sensitivity for detection of rifampicin, isoniazid and MDR-TB resistance by GenoType® MTBDRplus assay was 98.0%, 98.4% and 98.2% respectively. Out of 55 MDR-TB strains, 45 (81.8%), 52 (94.5%) and 17 (30.9%) strains showed mutation in rpoB, katG and inhA genes respectively (P < 0.05). The most prominent mutations in rpoB, katG and inhA genes were; 37 (67.3%) in S531L, 52 (94.5%) in S315T1 and 11 (20%) in C15T regions respectively (P < 0.05). Our study demonstrated a high concordance between the GenoType® MTBDRplus assay resistance patterns and those were observed by conventional DST with good sensitivity, specificity with short turnaround times and to control new cases of MDR-TB in countries with a high prevalence of MDR-TB.

  7. An Implantable MEMS Drug Delivery Device for Rapid Delivery in Ambulatory Emergency Care

    Science.gov (United States)

    2009-06-01

    vol. 32, pp. 377-379, 2000. I. Singer and H. L. Edmonds, "Head-up tilt testing predicts syncope during ventricular tachycardia in implantable... pulse through it, as has been demonstrated in the past (Maloney, 2005). The limitations of this solution are: the significant increase in current to...H. Brem, M. J. Cima, and R. Langer, "Multi- pulse drug delivery from a resorbable polymeric microchip device," Nature Materials, vol. 2, pp. 767-772

  8. Combining in vitro and in silico methods for better prediction of surfactant effects on the absorption of poorly water soluble drugs-a fenofibrate case example.

    Science.gov (United States)

    Berthelsen, Ragna; Sjögren, Erik; Jacobsen, Jette; Kristensen, Jakob; Holm, René; Abrahamsson, Bertil; Müllertz, Anette

    2014-10-01

    The aim of this study was to develop a sensitive and discriminative in vitro-in silico model able to simulate the in vivo performance of three fenofibrate immediate release formulations containing different surfactants. In addition, the study was designed to investigate the effect of dissolution volume when predicting the oral bioavailability of the formulations. In vitro dissolution studies were carried out using the USP apparatus 2 or a mini paddle assembly, containing 1000 mL or 100mL fasted state biorelevant medium, respectively. In silico simulations of small intestinal absorption were performed using the GI-Sim absorption model. All simulation runs were performed twice adopting either a total small intestinal volume of 533 mL or 105 mL, in order to examine the implication of free luminal water volumes for the in silico predictions. For the tested formulations, the use of a small biorelevant dissolution volume was critical for in vitro-in silico prediction of drug absorption. Good predictions, demonstrating rank order in vivo-in vitro-in silico correlations for Cmax, were obtained with in silico predictions utilizing a 105 mL estimate for the human intestinal water content combined with solubility and dissolution data performed in a mini paddle apparatus with 100mL fasted state simulated media. Copyright © 2014. Published by Elsevier B.V.

  9. Ultra-fast X-ray absorption spectroscopy for the study of matter in transient regime; Spectroscopie d'absorption ultra-rapide de rayonnement X pour l'etude de la matiere en regime transitoire

    Energy Technology Data Exchange (ETDEWEB)

    Lecherbourg, L

    2007-12-15

    In this work, we study the physics of dense matter, plasmas or solids, using X-ray absorption spectroscopy. Through the use of sources produced by laser-matter interaction, we have measured the absorption spectra of aluminum and bromine plasmas, as well as those of vanadium dioxide (VO{sub 2}). The measurement of absorption coefficients allows us to probe the dense matter and to study its properties. The experiments are carried out following the same principle: they use the same experimental set-up, called pump-probe. When the matter is dense, the absorption properties of an atom are modified by the surrounding environment. In a plasma, it is mainly the bound- bound transitions which are altered: the shapes of those spectral rays are modified. In a solid, the position of the neighbouring atoms in relation to the absorbing atom modify the structure of absorption levels (bound-free transition). The study of this structure allows us to measure the parameters of the material, and provides information such as the state of the electronic band or the interatomic gaps. The experiments carried out at the LULI have allowed us to probe plasmas in the relatively unknown regime of the Warm Dense Matter. One of the key parameters is that the plasma is characterised independently (FDI diagnostic). It allows for a better comparison of the measured absorption against a calculation made with the numerical model OPA-S. The experiments carried out at INRS have led to the realisation of an experimental system having the characteristics which allow the study of the dynamics of solids showing ultra-fast phase transition. For those experiments, we have used vanadium dioxide as a model system allowing us to test the feasibility of the method. (author)

  10. Common ocular effects reported to a poison control center after systemic absorption of drugs in therapeutic and toxic doses.

    Science.gov (United States)

    Slattery, Ann; Liebelt, Erica; Gaines, LaDonna A

    2014-11-01

    Ocular effects resulting from medications assist toxicologists in determining substances involved when treating a poisoned patient. The intention of this review is to discuss the most common ocular effects, the medications that cause them, and the mechanisms by which they occur. According to National Poison Data System, the most common reported ocular effects following a drug ingestion/injection/inhalation are mydriasis, miosis, and nystagmus. The most common drug/drug classes reported to a regional poison control center causing these ocular effects include the following: first, mydriasis - amphetamines and diphenhydramine; second, miosis - clonidine and opioids; third, nystagmus - dextromethorphan. However, many other drugs/substances can cause these effects along with other systemic effects. Ocular findings are a pertinent component of any patient assessment involving therapeutic and/or toxic exposure to medications and other substances.

  11. Secreted phospholipase A(2) as a new enzymatic trigger mechanism for localised liposomal drug release and absorption in diseased tissue

    DEFF Research Database (Denmark)

    Davidsen, Jesper; Jørgensen, K.; Andresen, Thomas Lars

    2003-01-01

    Polymer-coated liposomes can act as versatile drug-delivery systems due to long vascular circulation time and passive targeting by leaky blood vessels in diseased tissue. We present an experimental model system illustrating a new principle for improved and programmable drug-delivery, which takes ......-based proenhancers or prodestabilisers into the liposome carrier, which automatically becomes activated by PLA2 only at the diseased target sites, such as inflamed or cancerous tissue....

  12. A heuristic model to quantify the impact of excess cyclodextrin on oral drug absorption from aqueous solution

    DEFF Research Database (Denmark)

    Olesen, Niels Erik; Westh, Peter; Holm, René

    2016-01-01

    , the cyclodextrin concentration in the drug product must be higher than the amount needed to solubilise the compound, due to the displacement of the drug from the cyclodextrin cavity by bile salts in the intestinal lumen. On the other hand, dosing cyclodextrin at View the MathML source>DtotSC is expected to result...... the implication of having excess cyclodextrin in an oral solution....

  13. Has introduction of rapid drug susceptibility testing at diagnosis impacted treatment outcomes among previously treated tuberculosis patients in Gujarat, India?

    Science.gov (United States)

    Dave, Paresh; Vadera, Bhavin; Kumar, Ajay M V; Chinnakali, Palanivel; Modi, Bhavesh; Solanki, Rajesh; Patel, Pranav; Patel, Prakash; Pujara, Kirit; Nimavat, Pankaj; Shah, Amar; Bharaswadkar, Sandeep; Rade, Kiran; Parmar, Malik; Nair, Sreenivas Achuthan

    2015-01-01

    Revised National TB Control Programme (RNTCP) in India recommends that all previously-treated TB (PT) patients are offered drug susceptibility testing (DST) at diagnosis, using rapid diagnostics and screened out for rifampicin resistance before being treated with standardized, eight-month, retreatment regimen. This is intended to improve the early diagnosis of rifampicin resistance and its appropriate management and improve the treatment outcomes among the rest of the patients. In this state-wide study from Gujarat, India, we assess proportion of PT patients underwent rapid DST at diagnosis and the impact of this intervention on their treatment outcomes. This is a retrospective cohort study involving review of electronic patient-records maintained routinely under RNTCP. All PT patients registered for treatment in Gujarat during January-June 2013 were included. Information on DST and treatment outcomes were extracted from 'presumptive DR-TB patient register' and TB treatment register respectively. We performed a multivariate analysis to assess if getting tested is independently associated with unfavourable outcomes (death, loss-to-follow-up, failure, transfer out). Of 5,829 PT patients, 5306(91%) were tested for drug susceptibility with rapid diagnostics. Overall, 71% (4,113) TB patients were successfully treated - 72% among tested versus 60% among non-tested. Patients who did not get tested at diagnosis had a 34% higher risk of unsuccessful outcomes as compared to those who got tested (aRR - 1.34; 95% CI 1.20-1.50) after adjusting for age, sex, HIV status and type of TB. Unfavourable outcomes (particularly failure and switched to category IV) were higher among INH-resistant patients (39%) as compared to INH-sensitive (29%). Offering DST at diagnosis improved the treatment outcomes among PT patients. However, even among tested, treatment outcomes remained suboptimal and were related to INH resistance and high loss-to-follow-up. These need to be addressed urgently

  14. Virtual target screening to rapidly identify potential protein targets of natural products in drug discovery

    Directory of Open Access Journals (Sweden)

    Yuri Pevzner

    2015-08-01

    Full Text Available Inherent biological viability and diversity of natural products make them a potentially rich source for new therapeutics. However, identification of bioactive compounds with desired therapeutic effects and identification of their protein targets is a laborious, expensive process. Extracts from organism samples may show desired activity in phenotypic assays but specific bioactive compounds must be isolated through further separation methods and protein targets must be identified by more specific phenotypic and in vitro experimental assays. Still, questions remain as to whether all relevant protein targets for a compound have been identified. The desire is to understand breadth of purposing for the compound to maximize its use and intellectual property, and to avoid further development of compounds with insurmountable adverse effects. Previously we developed a Virtual Target Screening system that computationally screens one or more compounds against a collection of virtual protein structures. By scoring each compound-protein interaction, we can compare against averaged scores of synthetic drug-like compounds to determine if a particular protein would be a potential target of a compound of interest. Here we provide examples of natural products screened through our system as we assess advantages and shortcomings of our current system in regards to natural product drug discovery.

  15. Virtual target screening to rapidly identify potential protein targets of natural products in drug discovery

    Directory of Open Access Journals (Sweden)

    Yuri Pevzner

    2014-05-01

    Full Text Available Inherent biological viability and diversity of natural products make them a potentially rich source for new therapeutics. However, identification of bioactive compounds with desired therapeutic effects and identification of their protein targets is a laborious, expensive process. Extracts from organism samples may show desired activity in phenotypic assays but specific bioactive compounds must be isolated through further separation methods and protein targets must be identified by more specific phenotypic and in vitro experimental assays. Still, questions remain as to whether all relevant protein targets for a compound have been identified. The desire is to understand breadth of purposing for the compound to maximize its use and intellectual property, and to avoid further development of compounds with insurmountable adverse effects. Previously we developed a Virtual Target Screening system that computationally screens one or more compounds against a collection of virtual protein structures. By scoring each compound-protein interaction, we can compare against averaged scores of synthetic drug-like compounds to determine if a particular protein would be a potential target of a compound of interest. Here we provide examples of natural products screened through our system as we assess advantages and shortcomings of our current system in regards to natural product drug discovery.

  16. First Time Rapid and Accurate Detection of Massive Number of Metal Absorption Lines in the Early Universe Using Deep Neural Network

    Science.gov (United States)

    Zhao, Yinan; Ge, Jian; Yuan, Xiaoyong; Li, Xiaolin; Zhao, Tiffany; Wang, Cindy

    2018-01-01

    Metal absorption line systems in the distant quasar spectra have been used as one of the most powerful tools to probe gas content in the early Universe. The MgII λλ 2796, 2803 doublet is one of the most popular metal absorption lines and has been used to trace gas and global star formation at redshifts between ~0.5 to 2.5. In the past, machine learning algorithms have been used to detect absorption lines systems in the large sky survey, such as Principle Component Analysis, Gaussian Process and decision tree, but the overall detection process is not only complicated, but also time consuming. It usually takes a few months to go through the entire quasar spectral dataset from each of the Sloan Digital Sky Survey (SDSS) data release. In this work, we applied the deep neural network, or “ deep learning” algorithms, in the most recently SDSS DR14 quasar spectra and were able to randomly search 20000 quasar spectra and detect 2887 strong Mg II absorption features in just 9 seconds. Our detection algorithms were verified with previously released DR12 and DR7 data and published Mg II catalog and the detection accuracy is 90%. This is the first time that deep neural network has demonstrated its promising power in both speed and accuracy in replacing tedious, repetitive human work in searching for narrow absorption patterns in a big dataset. We will present our detection algorithms and also statistical results of the newly detected Mg II absorption lines.

  17. Desorption electrospray ionisation mass spectrometry: A rapid screening tool for veterinary drug preparations and forensic samples from hormone crime investigations

    Energy Technology Data Exchange (ETDEWEB)

    Nielen, M.W.F. [RIKILT Institute of Food Safety, P.O. Box 230, 6700 AE Wageningen (Netherlands); Wageningen University, Laboratory of Organic Chemistry, Dreijenplein 8, 6703 HB Wageningen (Netherlands)], E-mail: michel.nielen@wur.nl; Hooijerink, H. [RIKILT Institute of Food Safety, P.O. Box 230, 6700 AE Wageningen (Netherlands); Claassen, F.C. [Wageningen University, Laboratory of Organic Chemistry, Dreijenplein 8, 6703 HB Wageningen (Netherlands); Engelen, M.C. van [RIKILT Institute of Food Safety, P.O. Box 230, 6700 AE Wageningen (Netherlands); Beek, T.A. van [Wageningen University, Laboratory of Organic Chemistry, Dreijenplein 8, 6703 HB Wageningen (Netherlands)

    2009-04-01

    Hormone and veterinary drug screening and forensics can benefit from the recent developments in desorption electrospray ionisation (DESI) mass spectrometry (MS). In this work the feasibility of DESI application has been studied. Using a linear ion trap or quadrupole time-of-flight (TOF) MS instrument both full-scan and data-dependent collision-induced dissociation MS{sup n} spectra were acquired in seconds without sample preparation. Preliminary data are presented for the rapid screening of (pro)hormone supplement samples, an illegal steroid cocktail and forensic samples from veterinary drug investigations. The potential of this DESI approach is clearly demonstrated since compounds observed could be independently confirmed by liquid chromatography/TOFMS with accurate mass measurement, and/or proton nuclear magnetic resonance spectroscopy. Specific concerns related to false-positive and false-negative findings due to limitations in quantification and memory-effects are briefly discussed. It is envisaged that DESI will achieve a prominent role in hormone and veterinary drug analysis in the near future.

  18. The effect of E. coli STa enterotoxin on the absorption of weakly dissociable drugs from rat proximal jejunum in vivo.

    OpenAIRE

    McEwan, G. T.; Lucas, M. L.

    1990-01-01

    1. The effect of E. coli heat stable (STa) enterotoxin on the absorption of radio-labelled weak electrolytes and their appearance in peripheral blood was assessed in vivo by use of an intestinal recirculation procedure. 2. STa reduced the luminal disappearance (P less than 0.02) and peripheral blood appearance (P less than 0.02) of label from salicylic acid as well as the luminal disappearance (P less than 0.02) of diphenylhydantoin. 3. In contrast, STa increased the appearance in peripheral ...

  19. Effect of pH and comedication on gastrointestinal absorption of posaconazole: monitoring of intraluminal and plasma drug concentrations.

    Science.gov (United States)

    Walravens, Jeroen; Brouwers, Joachim; Spriet, Isabel; Tack, Jan; Annaert, Pieter; Augustijns, Patrick

    2011-11-01

    Posaconazole (Noxafil®) is an extended-spectrum triazole antifungal agent for prevention and treatment of invasive fungal infections. An inadequate dietary intake and abnormal gastric pH levels are common in critically ill patients receiving antifungal treatment with posaconazole, resulting in unpredictable bioavailability and sub-therapeutic plasma concentrations. This study was carried out to elucidate the impact of pH on posaconazole absorption and to explore the underlying mechanisms of enhanced intestinal absorption when coadministering an acidic carbonated beverage. In contrast to previously published studies, in which only plasma concentrations were determined, we also explored the gastric and intestinal behaviour of posaconazole after a single oral dose. A crossover study was performed in five healthy subjects. A single dose (10 mL) of posaconazole suspension (40 mg/mL) was administered orally in four different conditions: with 330 mL of water (condition 1); with 330 mL of a cola beverage [Coca-Cola®] (condition 2); with 330 mL of water following intake of the proton pump inhibitor esomeprazole 40 mg once daily for 3 days (condition 3); or with 330 mL of Coca-Cola® following intake of esomeprazole 40 mg once daily for 3 days (condition 4). After administration, gastrointestinal fluid and plasma samples were collected at regular time points, and posaconazole concentrations were determined. Compared with administration with water, coadministration of Coca-Cola® did not alter the pH of the intraluminal environment but did significantly increase posaconazole gastric concentrations (+102%; p Coca-Cola® and prolonged gastric residence. Coadministration of esomeprazole led to an increased gastric pH, which was accompanied by decreased posaconazole absorption; the mean plasma and gastric area under the concentration-time curve (AUC) values decreased by 37% and 84%, respectively. Simultaneous intake of Coca-Cola® could not completely compensate for the

  20. Elongation of fibers from highly viscous dextran solutions enables fabrication of rapidly dissolving drug carrying fabrics.

    Science.gov (United States)

    Frampton, John P; Lai, David; Lounds, Maxwell; Chung, Kyeongwoon; Kim, Jinsang; Mansfield, John F; Takayama, Shuichi

    2015-01-28

    A simple method is presented for forming thread-like fibers from highly viscous dextran solutions. Based on the cohesive and adhesive forces between a dextran solution and the substrate to which it is applied, multiple fibers of approximately 10 μm in diameter can be elongated simultaneously. These fibers can be woven into multiple layers to produce fabrics of varying fiber orientations and mechanical properties. Various bioactive agents can be incorporated into the dextran solution prior to fiber formation, including hemostatic and antibiotic agents. Fabrics containing thrombin are capable of coagulating human platelet poor plasma in vitro. Fabrics containing antibiotics are capable of suppressing bacterial growth in a disk diffusion assay. These data suggest that this new material composed entirely of dextran has promise as a drug delivery component in wound dressings. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Rapid evolution of virulence and drug resistance in the emerging zoonotic pathogen Streptococcus suis.

    Directory of Open Access Journals (Sweden)

    Matthew T G Holden

    2009-07-01

    Full Text Available Streptococcus suis is a zoonotic pathogen that infects pigs and can occasionally cause serious infections in humans. S. suis infections occur sporadically in human Europe and North America, but a recent major outbreak has been described in China with high levels of mortality. The mechanisms of S. suis pathogenesis in humans and pigs are poorly understood.The sequencing of whole genomes of S. suis isolates provides opportunities to investigate the genetic basis of infection. Here we describe whole genome sequences of three S. suis strains from the same lineage: one from European pigs, and two from human cases from China and Vietnam. Comparative genomic analysis was used to investigate the variability of these strains. S. suis is phylogenetically distinct from other Streptococcus species for which genome sequences are currently available. Accordingly, approximately 40% of the approximately 2 Mb genome is unique in comparison to other Streptococcus species. Finer genomic comparisons within the species showed a high level of sequence conservation; virtually all of the genome is common to the S. suis strains. The only exceptions are three approximately 90 kb regions, present in the two isolates from humans, composed of integrative conjugative elements and transposons. Carried in these regions are coding sequences associated with drug resistance. In addition, small-scale sequence variation has generated pseudogenes in putative virulence and colonization factors.The genomic inventories of genetically related S. suis strains, isolated from distinct hosts and diseases, exhibit high levels of conservation. However, the genomes provide evidence that horizontal gene transfer has contributed to the evolution of drug resistance.

  2. Rapid evolution of virulence and drug resistance in the emerging zoonotic pathogen Streptococcus suis.

    Science.gov (United States)

    Holden, Matthew T G; Hauser, Heidi; Sanders, Mandy; Ngo, Thi Hoa; Cherevach, Inna; Cronin, Ann; Goodhead, Ian; Mungall, Karen; Quail, Michael A; Price, Claire; Rabbinowitsch, Ester; Sharp, Sarah; Croucher, Nicholas J; Chieu, Tran Bich; Mai, Nguyen Thi Hoang; Diep, To Song; Chinh, Nguyen Tran; Kehoe, Michael; Leigh, James A; Ward, Philip N; Dowson, Christopher G; Whatmore, Adrian M; Chanter, Neil; Iversen, Pernille; Gottschalk, Marcelo; Slater, Josh D; Smith, Hilde E; Spratt, Brian G; Xu, Jianguo; Ye, Changyun; Bentley, Stephen; Barrell, Barclay G; Schultsz, Constance; Maskell, Duncan J; Parkhill, Julian

    2009-07-15

    Streptococcus suis is a zoonotic pathogen that infects pigs and can occasionally cause serious infections in humans. S. suis infections occur sporadically in human Europe and North America, but a recent major outbreak has been described in China with high levels of mortality. The mechanisms of S. suis pathogenesis in humans and pigs are poorly understood. The sequencing of whole genomes of S. suis isolates provides opportunities to investigate the genetic basis of infection. Here we describe whole genome sequences of three S. suis strains from the same lineage: one from European pigs, and two from human cases from China and Vietnam. Comparative genomic analysis was used to investigate the variability of these strains. S. suis is phylogenetically distinct from other Streptococcus species for which genome sequences are currently available. Accordingly, approximately 40% of the approximately 2 Mb genome is unique in comparison to other Streptococcus species. Finer genomic comparisons within the species showed a high level of sequence conservation; virtually all of the genome is common to the S. suis strains. The only exceptions are three approximately 90 kb regions, present in the two isolates from humans, composed of integrative conjugative elements and transposons. Carried in these regions are coding sequences associated with drug resistance. In addition, small-scale sequence variation has generated pseudogenes in putative virulence and colonization factors. The genomic inventories of genetically related S. suis strains, isolated from distinct hosts and diseases, exhibit high levels of conservation. However, the genomes provide evidence that horizontal gene transfer has contributed to the evolution of drug resistance.

  3. Property profiling of biosimilar mucus in a novel mucus-containing in vitro model for assessment of intestinal drug absorption

    DEFF Research Database (Denmark)

    Bøgh, Marie; Baldursdóttir, Stefania G; Müllertz, Anette

    2014-01-01

    Oral delivery of drugs, including peptide and protein therapeutics, can be impeded by the presence of the mucus surface-lining the intestinal epithelium. The aim of the present project was to design and characterize biosimilar mucus compatible with Caco-2 cell monolayers cultured in vitro...... the Caco-2 cell monolayer. When combined with the Caco-2 cell monolayers, the final biosimilar mucus was found to significantly affect the permeability profiles for hydrophobic and hydrophilic small and large model drug compounds in different ways. In conclusion, the present study describes an improvement...... of the biorelevance of the Caco-2 cell culture model by application of mucus, resulting in an in vitro model of oral mucosa suitable for future assessment of innovative drug delivery approaches....

  4. Rapid analysis of interaction between six drugs and β2 -adrenergic receptor by injection amount-dependent method.

    Science.gov (United States)

    Zeng, Kaizhu; Wang, Jing; Sun, Zhenyu; Li, Qian; Liao, Sha; Zhao, Xinfeng; Zheng, Xiaohui

    2017-06-01

    Drug-protein interaction analysis has become a considerable topic in life science which includes clarifying protein functions, explaining drug action mechanisms and uncovering novel drug candidates. This work was to determine the association constants (KA ) of six drugs to β2 -adrenergic receptor by injection amount-dependent method using stationary phase containing the immobilized receptor. The values of KA were calculated to be (25.85 ± 0.035) × 104  m-1 for clorprenaline, (42.51 ± 0.054) × 104  m-1 for clenbuterol, (6.67 ± 0.008) × 104  m-1 for terbutaline, (33.99 ± 0.025) × 104  m-1 for tulobuterol, (7.59 ± 0.011) × 104  m-1 for salbutamol and (78.52 ± 0.087) × 104  m-1 for bambuterol. This rank order agreed well with the data determined by zonal elution, frontal analysis and nonlinear chromatography, even using different batches of β2 -AR column. A good correlation was found between the association constants by the current method and radio-ligand binding assay. Our data indicates that the injection amount-dependent method is a powerful alternative for rapid analysis of ligand-receptor interactions. Copyright © 2016 John Wiley & Sons, Ltd.

  5. Introducing rapid diagnostic tests for malaria into drug shops in Uganda: design and implementation of a cluster randomized trial.

    Science.gov (United States)

    Mbonye, Anthony K; Magnussen, Pascal; Chandler, Clare I R; Hansen, Kristian S; Lal, Sham; Cundill, Bonnie; Lynch, Caroline A; Clarke, Siân E

    2014-07-29

    An intervention was designed to introduce rapid diagnostics tests for malaria (mRDTs) into registered drug shops in Uganda to encourage rational and appropriate treatment of malaria with artemisinin-based combination therapy (ACT). We conducted participatory training of drug shop vendors and implemented supporting interventions to orientate local communities (patients) and the public sector (health facility staff and district officials) to the behavioral changes in diagnosis, treatment and referral being introduced in drug shops. The intervention was designed to be evaluated through a cluster randomized trial. In this paper, we present detailed design, implementation and evaluation experiences in order to help inform future studies of a complex nature. Three preparatory studies (formative, baseline and willingness-to-pay) were conducted to explore perceptions on diagnosis and treatment of malaria at drug shops, and affordable prices for mRDTs and ACTs in order to inform the design of the intervention and implementation modalities. The intervention required careful design with the intention to be acceptable, sustainable and effective. Critical components of intervention were: community sensitization and creating awareness, training of drug shop vendors to diagnose malaria with mRDTs, treat and refer customers to formal health facilities, giving pre-referral rectal artesunate and improved record-keeping. The primary outcome was the proportion of patients receiving appropriately-targeted treatment with ACT, evaluated against microscopy on a research blood slide. Introducing mRDTs in drug shops may seem simple, but our experience of intervention design, conduct and evaluation showed this to be a complex process requiring multiple interventions and evaluation components drawing from a combination of epidemiological, social science and health economics methodologies. The trial was conducted in phases sequenced such that each benefited from the other. The main challenges

  6. Neurophysiological basis of rapid eye movement sleep behavior disorder: informing future drug development

    Directory of Open Access Journals (Sweden)

    Jennum P

    2016-04-01

    Full Text Available Poul Jennum, Julie AE Christensen, Marielle Zoetmulder Department of Clinical Neurophysiology, Faculty of Health Sciences, Danish Center for Sleep Medicine, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark Abstract: Rapid eye movement (REM sleep behavior disorder (RBD is a parasomnia characterized by a history of recurrent nocturnal dream enactment behavior and loss of skeletal muscle atonia and increased phasic muscle activity during REM sleep: REM sleep without atonia. RBD and associated comorbidities have recently been identified as one of the most specific and potentially sensitive risk factors for later development of any of the alpha-synucleinopathies: Parkinson’s disease, dementia with Lewy bodies, and other atypical parkinsonian syndromes. Several other sleep-related abnormalities have recently been identified in patients with RBD/Parkinson’s disease who experience abnormalities in sleep electroencephalographic frequencies, sleep–wake transitions, wake and sleep stability, occurrence and morphology of sleep spindles, and electrooculography measures. These findings suggest a gradual involvement of the brainstem and other structures, which is in line with the gradual involvement known in these disorders. We propose that these findings may help identify biomarkers of individuals at high risk of subsequent conversion to parkinsonism. Keywords: motor control, brain stem, hypothalamus, hypocretin

  7. Rapid detection of drugs of abuse in saliva using surface enhanced Raman spectroscopy and microfluidics.

    Science.gov (United States)

    Andreou, Chrysafis; Hoonejani, Mehran R; Barmi, Meysam R; Moskovits, Martin; Meinhart, Carl D

    2013-08-27

    We present a microfluidic device that detects trace concentrations of drugs of abuse in saliva within minutes using surface-enhanced Raman spectroscopy (SERS). Its operation is demonstrated using methamphetamine. The detection scheme exploits concentration gradients of chemicals, fostered by the laminar flow in the device, to control the interactions between the analyte, silver nanoparticles (Ag-NPs), and a salt. Also, since all species interact while advecting downstream, the relevant reaction coordinates occur with respect to the position in the channel. The system was designed to allow the analyte first to diffuse into the side stream containing the Ag-NPs, on which it is allowed to adsorb, before salt ions are introduced, causing the Ag-NPs to aggregate, and so creating species with strong SERS signal. The device allows partial separation via diffusion of the analyte from the complex mixture. Also, the reproducible salt-induced NP aggregation decouples the aggregation reaction (necessary for strong SERS) from the analyte concentration or charge. This method enables the creation of a region where detection of the analyte of interest via SERS is optimal, and dramatically extends the classes of molecules and quality of signals that can be measured using SERS, compared to bulk solution methods. The spatial distribution of the SERS signals was used to map the degree of nanoparticle aggregation and species diffusion in the channel, which, together with numerical simulations, was used to describe the kinetics of the colloid aggregation reaction, and to determine the optimal location in the channel for SERS interrogation.

  8. The use of recently described ionisation techniques for the rapid analysis of some common drugs and samples of biological origin.

    Science.gov (United States)

    Williams, Jonathan P; Patel, Vibhuti J; Holland, Richard; Scrivens, James H

    2006-01-01

    Three ionisation techniques that require no sample preparation or extraction prior to mass analysis have been used for the rapid analysis of pharmaceutical tablets and ointments. These methods were (i) the novel direct analysis in real time (DART), (ii) desorption electrospray ionisation (DESI), and (iii) desorption atmospheric pressure chemical ionisation (DAPCI). The performance of the three techniques was investigated for a number of common drugs. Significant differences between these approaches were observed. For compounds of moderate to low polarity DAPCI produced more effective ionisation. Accurate DESI and DAPCI tandem mass spectra were obtained and these greatly enhance the selectivity and information content of the experiment. The detection from human skin of the active ingredients from ointments is reported together with the detection of ibuprofen metabolites in human urine. Copyright 2006 John Wiley & Sons, Ltd.

  9. Fast mouse PK (Fast PK): a rapid screening method to increase pharmacokinetic throughput in pre-clinical drug discovery.

    Science.gov (United States)

    Reddy, Jitendar; Madishetti, Sreedhar; Vachaspati, Prakash R

    2012-09-29

    We describe a rapid screening methodology for performing pharmacokinetic (PK) studies in mice called Fast PK. In this Fast PK method, two mice were used per compound and four blood samples were collected from each mouse. The sampling times were staggered (sparse sampling) between the two mice, thus yielding complete PK profile in singlicate across eight time points. The plasma PK parameters from Fast PK were comparable to that obtained from conventional PK methods. This method has been used to rapidly screen compounds in the early stages of drug discovery and about 600 compounds have been profiled in the last 3 years, which has resulted in reduction in the usage of mice by 800 per year in compliance with the 3R principles of animal ethics. In addition, this Fast PK method can also help in evaluating the PK parameters from the same set of animals used in safety/toxicology/efficacy studies without the need for satellite groups. Copyright © 2012 Elsevier B.V. All rights reserved.

  10. Polypyrrole solid phase microextraction: A new approach to rapid sample preparation for the monitoring of antibiotic drugs

    Energy Technology Data Exchange (ETDEWEB)

    Szultka, Malgorzata [Department of Environmental Chemistry and Bioanalytics, Faculty of Chemistry, Nicolaus, Copernicus University, Gagarin 7, 87-100 Torun (Poland); Kegler, Ricarda [Institute of Clinical Pharmacology, University of Rostock, Schillingallee 70, D-18057 Rostock (Germany); Fuchs, Patricia [Department of Anaesthesia and Intensive Care, University of Rostock, Schillingallee 35, D-18057 Rostock (Germany); Olszowy, Pawel [Department of Environmental Chemistry and Bioanalytics, Faculty of Chemistry, Nicolaus, Copernicus University, Gagarin 7, 87-100 Torun (Poland); Miekisch, Wolfram; Schubert, Jochen K. [Department of Anaesthesia and Intensive Care, University of Rostock, Schillingallee 35, D-18057 Rostock (Germany); Buszewski, Boguslaw [Department of Environmental Chemistry and Bioanalytics, Faculty of Chemistry, Nicolaus, Copernicus University, Gagarin 7, 87-100 Torun (Poland); Mundkowski, Ralf G., E-mail: ralf.mundkowski@med.uni-rostock.de [Institute of Clinical Pharmacology, University of Rostock, Schillingallee 70, D-18057 Rostock (Germany)

    2010-05-14

    Simple or even rapid bioanalytical methods are rare, since they generally involve complicated, time-consuming sample preparation from the biological matrices like LLE or SPE. SPME provides a promising approach to overcome these limitations. The full potential of this innovative technique for medical diagnostics, pharmacotherapy or biochemistry has not been tapped yet. In-house manufactured SPME probes with polypyrrole (PPy) coating were evaluated using three antibiotics of high clinical relevance - linezolid, daptomycin, and moxifloxacin - from PBS, plasma, and whole blood. The PPy coating was characterised by scanning electron microscopy. Influences of pH, inorganic salt, and blood anticoagulants were studied for optimum performance. Extraction yields were determined from stagnant media as well as re-circulating human blood using the heart-and-lung machine model system. The PPy-SPME fibres showed high extraction yields, particularly regarding linezolid. The reproducibility of the method was optimised to achieve RSDs of 9% or 17% and 7% for SPME from stagnant or re-circulating blood using fresh and re-used fibres, respectively. The PPy-SPME approach was demonstrated to meet the requirements of therapeutic monitoring of the drugs tested, even from re-circulating blood at physiological flow rates. SPME represents a rapid and simple dual-step procedure with potency to significantly reduce the effort and expenditure of complicated sample preparations in biomedical analysis.

  11. Comparison of the rates of disintegration, gastric emptying, and drug absorption following administration of a new and a conventional paracetamol formulation, using gamma scintigraphy.

    Science.gov (United States)

    Kelly, Kilian; O'Mahony, Bridget; Lindsay, Blythe; Jones, Tamara; Grattan, Tim J; Rostami-Hodjegan, Amin; Stevens, Howard N E; Wilson, Clive G

    2003-10-01

    To investigate the hypothesis that faster drug absorption from a new paracetamol formulation containing sodium bicarbonate compared to that from a conventional formulation results from a combination of enhanced gastric emptying and disintegration/dissolution. Each formulation was administered in both fasted and fed states to 12 healthy volunteers. Gastric emptying and disintegration times were assessed by gamma scintigraphy, and serum paracetamol concentrations were determined by HPLC. The mean time to complete disintegration of the new tablets was faster than that for conventional tablets in both fasted (10.2 min vs. 22.5 min) and fed (14.3 min vs. 46.4 min) states, although this difference was statistically significant in the fed state only (p = 0.0053). Mean gastric emptying times for the new tablets, as measured by t50 and t90, were also faster than those for conventional tablets in both fasted (t50 = 22.4 min vs. 47.5 min, t90 = 30.9 min vs. 64.1 min) and fed (t50 = 76.9 min vs. 106.4 min, t90 = 152.7 min vs. 155.5 min) states, although these differences were not statistically significant. Two subjects showed dramatically retarded gastric emptying of the new tablets in the fasted state: if these atypical data are excluded, the differences in both t50 and t90 in the fasted state are significant (p = 0.0110 and 0.0035, respectively). Rate of paracetamol absorption reflected the gastric emptying profiles as shown by significant correlation of emptying times with partial AUC. It would seem that a combination of faster disintegration and gastric emptying of the new tablets is responsible for the faster rate of absorption of paracetamol from PA compared to P observed in both this study and in previous studies. The differences in gastric emptying are more pronounced in the fasted state, and the differences in disintegration are more pronounced in the fed state.

  12. Effect of piperine, a major component of black pepper, on the intestinal absorption of fexofenadine and its implication on food-drug interaction.

    Science.gov (United States)

    Jin, Ming-Ji; Han, Hyo-Kyung

    2010-04-01

    The present study aimed to investigate the effect of piperine, a major component of black pepper, on the oral exposure of fexofenadine in rats. Pharmacokinetic parameters of fexofenadine were determined in rats following an oral (10 mg/kg) or intravenous (5 mg/kg) administration of fexofenadine in the presence and absence of piperine (10 or 20 mg/kg, given orally). Compared to the control group given fexofenadine alone, the combined use of piperine increased the oral exposure (AUC) of fexofenadine by 180% to 190% while there was no significant change in C(max) and T(1/2) of fexofenadine in rats. The bioavailability of fexofenadine was increased by approximately 2-folds via the concomitant use of piperine. Furthermore, T(max) tends to be increased which might be attributed to the delayed gastric emptying in the presence of piperine. In contrast, piperine did not alter the intravenous pharmacokinetics of fexofenadine, implying that piperine may increase mainly the gastrointestinal absorption of fexofenadine rather than reducing hepatic extraction. In conclusion, piperine significantly enhanced the oral exposure of fexofenadine in rats likely by the inhibition of P-glycoprotein-mediated cellular efflux during the intestinal absorption, suggesting that the combined use of piperine or piperine-containing diet with fexofenadine may require close monitoring for potential drug-diet interactions.

  13. Biorelevant media for transport experiments in the Caco-2 model to evaluate drug absorption in the fasted and the fed state and their usefulness.

    Science.gov (United States)

    Markopoulos, C; Thoenen, F; Preisig, D; Symillides, M; Vertzoni, M; Parrott, N; Reppas, C; Imanidis, G

    2014-04-01

    In this work we developed and characterized transport media that simulate the composition of micellar phase of intestinal fluids in the fasted and, especially, in the fed state and are appropriate for evaluating intestinal drug permeability characteristics using the Caco-2 model (FaSSIF-TM(Caco) and FeSSIF-TM(Caco), respectively). Media composition was based on FaSSIF-V2 and FeSSIF-V2 and recently reported data on total lipid concentrations in the micellar phase of contents of the upper small intestine in the fasted and the fed state and was adapted for cell culture compatibility. Permeation data were evaluated by compartmental kinetic modeling. Permeability coefficients, P, of hydrophilic drugs were not affected by media composition. In contrast, P values of a series of lipophilic compounds measured with FaSSIF-TM(Caco) and FeSSIF-TM(Caco), and reflecting transport by diffusion were smaller than those obtained with a purely aqueous reference transport medium, aq-TM(Caco), following the rank order aq-TM(Caco)>FaSSIF-TM(Caco)>FeSSIF-TM(Caco). The decline of permeability values was stronger as lipophilicity of the compounds increased. Compared with values estimated using aq-TM(Caco), permeability was reduced, depending on the compound, by more than 20- to 100-fold when measured with FeSSIF-TM(Caco) whereas compound ranking in regard to the permeability characteristics was also affected. The impact of reduced P value on flux through the mucosa, hence on drug absorption, in combination with the drug amount loaded on colloidal particles needs to be taken into consideration in PBPK modeling especially when the food effect is evaluated. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. In Situ Perfusion Model in Rat Colon for Drug Absorption Studies: Comparison with Small Intestine and Caco-2 Cell Model.

    Science.gov (United States)

    Lozoya-Agullo, Isabel; González-Álvarez, Isabel; González-Álvarez, Marta; Merino-Sanjuán, Matilde; Bermejo, Marival

    2015-09-01

    Our aim is to develop and to validate the in situ closed loop perfusion method in rat colon and to compare with small intestine and Caco-2 cell models. Correlations with human oral fraction absorbed (Fa) and human colon fraction absorbed (Fa_colon) were developed to check the applicability of the rat colon model for controlled release (CR) drug screening. Sixteen model drugs were selected and their permeabilities assessed in rat small intestine and colon, and in Caco-2 monolayers. Correlations between colon/intestine/Caco-2 permeabilities versus human Fa and human Fa_colon have been explored to check model predictability and to apply a BCS approach in order to propose a cut off value for CR screening. Rat intestine perfusion with Doluisio's method and single-pass technique provided a similar range of permeabilities demonstrating the possibility of combining data from different laboratories. Rat colon permeability was well correlated with Caco-2 cell-4 days model reflecting a higher paracellular permeability. Rat colon permeabilities were also higher than human colon ones. In spite of the magnitude differences, a good sigmoidal relationship has been shown between rat colon permeabilities and human colon fractions absorbed, indicating that rat colon perfusion can be used for compound classification and screening of CR candidates. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  15. Designing and comparison study of rapid detection methods of resistance to injectable drugs in clinical strains of Mycobacterium tuberculosis

    Directory of Open Access Journals (Sweden)

    Fatemeh Salehi

    2012-01-01

    Full Text Available Introduction: In this study, some molecular methods were designed for rapid detection of resistance to kanamycin and amikacin.Materials and methods: Among 120 clinical isolates of mycobacterium tuberculosis, 70 strains were selected for evaluation of possible mutations. A PCR-RFLP method was designed for detection of wild type (using enzyme ajii and mutant from (BstFNI enzyme of the isolates. Furthermore, allele specific method (as PCR was designed for detection mutations in codons 1401 and 1402 gene rrs. Some selected isolates were sequenced.Results: In PCR-RFLP method, among the 70 strains examined by BstFNI enzyme, could detect 17 mutant strains among 24 phenotypicaly resistant and 44 non-mutant isolates from 46 susceptible isolates. The sensitivity of this method was %70.83 and specificity was %95.65 on the other hand, 12 mutant from 20 resistant strains and 29 non-mutant strains from 32 susceptible strains were detected by AjiI enzyme. The sensitivity and specificity of this method was 60 and %90.62, respectively. In MAS PCR, 3 mutants from 6 resistant strains and 12 non-mutants from 17 resistant strains were detected. The sensitivity of this method was 50 and specificity was 70.58. Results of sequencing method confirmed the results of molecular methods.Discussion and conclusion: PCR-RFLP method by BstFNI enzyme was the best method for rapid detection of Mycobacterium tuberculosis resistant to second-line injectable drugs and was recommended for routine use.

  16. Database Extraction of Metabolite Information of Drug Candidates: Analysis of 27 AstraZeneca Compounds with Human Absorption, Distribution, Metabolism, and Excretion Data.

    Science.gov (United States)

    Iegre, Jessica; Hayes, Martin A; Thompson, Richard A; Weidolf, Lars; Isin, Emre M

    2016-05-01

    As part of the drug discovery and development process, it is important to understand the human metabolism of a candidate drug prior to clinical studies. Preclinical in vitro and in vivo experiments across species are conducted to build knowledge concerning human circulating metabolites in preparation for clinical studies; therefore, the quality of these experiments is critical. Within AstraZeneca, all metabolite identification (Met-ID) information is stored in a global database using ACDLabs software. In this study, the Met-ID information derived from in vitro and in vivo studies for 27 AstraZeneca drug candidates that underwent human absorption, distribution, metabolism, and excretion studies was extracted from the database. The retrospective analysis showed that 81% of human circulating metabolites were previously observed in preclinical in vitro and/or in vivo experiments. A detailed analysis was carried out to understand which human circulating metabolites were not captured in the preclinical experiments. Metabolites observed in human hepatocytes and rat plasma but not seen in circulation in humans (extraneous metabolites) were also investigated. The majority of human specific circulating metabolites derive from multistep biotransformation reactions that may not be observed in in vitro studies within the limited time frame in which cryopreserved hepatocytes are active. Factors leading to the formation of extraneous metabolites in preclinical studies seemed to be related to species differences with respect to transporter activity, secondary metabolism, and enzyme kinetics. This retrospective analysis assesses the predictive value of Met-ID experiments and improves our ability to discriminate between metabolites expected to circulate in humans and irrelevant metabolites seen in preclinical studies. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  17. Country-wide surveillance of molecular markers of antimalarial drug resistance in Senegal by use of positive Malaria Rapid Diagnostic Tests

    DEFF Research Database (Denmark)

    Ndiaye, Magatte; Sow, Doudou; Nag, Sidsel

    2017-01-01

    of drug resistance. Therefore, surveillance of drug resistance in the malaria parasites is essential. The objective of this pilot study was to test the feasibility of routinely sampled malaria rapid diagnostic tests (RDTs) at a national scale to assess the temporal changes in the molecular profiles...... of antimalarial drug resistance markers of Plasmodium falciparum parasites. Overall, 9,549 positive malaria RDTs were collected from 14 health facilities across the country. A limited random set of RDTs were analyzed regarding Pfcrt gene polymorphisms at codon 72-76. Overall, a high but varied prevalence (> 50...

  18. Major reduction in anti-malarial drug consumption in Senegal after nation-wide introduction of malaria rapid diagnostic tests.

    Directory of Open Access Journals (Sweden)

    Sylla Thiam

    Full Text Available BACKGROUND: While WHO recently recommended universal parasitological confirmation of suspected malaria prior to treatment, debate has continued as to whether wide-scale use of rapid diagnostic tests (RDTs can achieve this goal. Adherence of health service personnel to RDT results has been poor in some settings, with little impact on anti-malarial drug consumption. The Senegal national malaria control programme introduced universal parasite-based diagnosis using malaria RDTs from late 2007 in all public health facilities. This paper assesses the impact of this programme on anti-malarial drug consumption and disease reporting. METHODS AND FINDINGS: Nationally-collated programme data from 2007 to 2009 including malaria diagnostic outcomes, prescription of artemisinin-based combination therapy (ACT and consumption of RDTs in public health facilities, were reviewed and compared. Against a marked seasonal variation in all-cause out-patient visits, non-malarial fever and confirmed malaria, parasite-based diagnosis increased nationally from 3.9% of reported malaria-like febrile illness to 86.0% over a 3 year period. The prescription of ACT dropped throughout this period from 72.9% of malaria-like febrile illness to 31.5%, reaching close equivalence to confirmed malaria (29.9% of 584,873 suspect fever cases. An estimated 516,576 courses of inappropriate ACT prescription were averted. CONCLUSIONS: The data indicate high adherence of anti-malarial prescribing practice to RDT results after an initial run-in period. The large reduction in ACT consumption enabled by the move from symptom-based to parasite-based diagnosis demonstrates that effective roll-out and use of malaria RDTs is achievable on a national scale through well planned and structured implementation. While more detailed information on management of parasite-negative cases is required at point of care level to assess overall cost-benefits to the health sector, considerable cost-savings were

  19. Major reduction in anti-malarial drug consumption in Senegal after nation-wide introduction of malaria rapid diagnostic tests.

    Science.gov (United States)

    Thiam, Sylla; Thior, Moussa; Faye, Babacar; Ndiop, Médoune; Diouf, Mamadou Lamine; Diouf, Mame Birame; Diallo, Ibrahima; Fall, Fatou Ba; Ndiaye, Jean Louis; Albertini, Audrey; Lee, Evan; Jorgensen, Pernille; Gaye, Oumar; Bell, David

    2011-04-06

    While WHO recently recommended universal parasitological confirmation of suspected malaria prior to treatment, debate has continued as to whether wide-scale use of rapid diagnostic tests (RDTs) can achieve this goal. Adherence of health service personnel to RDT results has been poor in some settings, with little impact on anti-malarial drug consumption. The Senegal national malaria control programme introduced universal parasite-based diagnosis using malaria RDTs from late 2007 in all public health facilities. This paper assesses the impact of this programme on anti-malarial drug consumption and disease reporting. Nationally-collated programme data from 2007 to 2009 including malaria diagnostic outcomes, prescription of artemisinin-based combination therapy (ACT) and consumption of RDTs in public health facilities, were reviewed and compared. Against a marked seasonal variation in all-cause out-patient visits, non-malarial fever and confirmed malaria, parasite-based diagnosis increased nationally from 3.9% of reported malaria-like febrile illness to 86.0% over a 3 year period. The prescription of ACT dropped throughout this period from 72.9% of malaria-like febrile illness to 31.5%, reaching close equivalence to confirmed malaria (29.9% of 584,873 suspect fever cases). An estimated 516,576 courses of inappropriate ACT prescription were averted. The data indicate high adherence of anti-malarial prescribing practice to RDT results after an initial run-in period. The large reduction in ACT consumption enabled by the move from symptom-based to parasite-based diagnosis demonstrates that effective roll-out and use of malaria RDTs is achievable on a national scale through well planned and structured implementation. While more detailed information on management of parasite-negative cases is required at point of care level to assess overall cost-benefits to the health sector, considerable cost-savings were achieved in ACT procurement. Programmes need to be allowed

  20. Evidence That P-glycoprotein Inhibitor (Elacridar)-Loaded Nanocarriers Improve Epidermal Targeting of an Anticancer Drug via Absorptive Cutaneous Transporters Inhibition.

    Science.gov (United States)

    Giacone, Daniela V; Carvalho, Vanessa F M; Costa, Soraia K P; Lopes, Luciana B

    2017-09-19

    Because P-glycoprotein (P-gp) plays an absorptive role in the skin, its pharmacological inhibition represents a strategy to promote cutaneous localization of anticancer agents that serve as its substrates, improving local efficacy while reducing systemic exposure. Here, we evaluated the ability of a nanoemulsion (NE) coencapsulating a P-gp inhibitor (elacridar) with the antitumor drug paclitaxel to promote epidermal targeting. Loaded NE displayed a nanometric size (45.2 ± 4.0 nm) and negative zeta potential (-4.2 ± 0.8 mV). Elacridar improved NE ability to inhibit verapamil-induced ATPase activity of P-gp; unloaded NE-inhibited P-gp when used at a concentration of 1500 μM, while elacridar encapsulation decreased this concentration by 3-fold (p p p P-gp inhibition and enabled epidermal targeting of paclitaxel, which in turn, can potentially reduce adverse effects associated with systemic exposure to anticancer therapy. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  1. Nonlinear system identification by Gustafson-Kessel fuzzy clustering and supervised local model network learning for the drug absorption spectra process.

    Science.gov (United States)

    Teslic, Luka; Hartmann, Benjamin; Nelles, Oliver; Skrjanc, Igor

    2011-12-01

    This paper deals with the problem of fuzzy nonlinear model identification in the framework of a local model network (LMN). A new iterative identification approach is proposed, where supervised and unsupervised learning are combined to optimize the structure of the LMN. For the purpose of fitting the cluster-centers to the process nonlinearity, the Gustafsson-Kessel (GK) fuzzy clustering, i.e., unsupervised learning, is applied. In combination with the LMN learning procedure, a new incremental method to define the number and the initial locations of the cluster centers for the GK clustering algorithm is proposed. Each data cluster corresponds to a local region of the process and is modeled with a local linear model. Since the validity functions are calculated from the fuzzy covariance matrices of the clusters, they are highly adaptable and thus the process can be described with a very sparse amount of local models, i.e., with a parsimonious LMN model. The proposed method for constructing the LMN is finally tested on a drug absorption spectral process and compared to two other methods, namely, Lolimot and Hilomot. The comparison between the experimental results when using each method shows the usefulness of the proposed identification algorithm.

  2. Application of volumetric absorptive microsampling device for quantification of tacrolimus in human blood as a model drug of high blood cell partition.

    Science.gov (United States)

    Kita, Kenji; Mano, Yuji

    2017-09-05

    Volumetric absorptive microsampling device (VAMS) was evaluated for bioanalysis of tacrolimus, which was used as a model drug with high blood cell partition. Aliquots of blood (ca. 10μL) with different hematocrits and fortified with tacrolimus were wicked up by VAMS and tacrolimus was extracted with a methanol-water mixture (1:1, v/v) via sonication. After chromatography on an AQUITY UPLC HSS T3 column (100×2.1 i.d., mm, 1.8μm), tacrolimus and the internal standard ascomycin, were detected in the positive ion mode with electrospray ionization by monitoring of transitions m/z 826.6→616.4 and m/z 814.6→604.0, respectively. An assay method to quantify tacrolimus from 1 to 250ng/mL in whole blood was qualified by ensuring that linearity, selectivity, intra- and inter-batch reproducibility, and stability were within the acceptance criteria. Consistent and high extraction recovery of tacrolimus was ensured from blood with low- (20%), mid- (45%), and high-hematocrit (65%) levels with minimal matrix effects. Apparent instability at ambient temperature or 4°C possibly due to reduced recovery suggests that tacrolimus in VAMS should be stored at -25°C until assay. Potential reduced recovery over time from VAMS should be taken into consideration in method optimization. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Fabrication and characterization of a rapid prototyped tissue engineering scaffold with embedded multicomponent matrix for controlled drug release

    DEFF Research Database (Denmark)

    Chen, Muwan; Le, Dang Q S; Hein, San

    2012-01-01

    showed that the scaffold was osteoinductive. The drug-release kinetics was investigated by loading doxorubicin into the scaffold. The scaffolds comprising nanoclay released up to 45% of the drug for up to 2 months, while the scaffold without nanoclay released 95% of the drug within 4 days. Therefore...

  4. Simultaneous Rapid Determination of the Solubility and Diffusion Coefficients of a Poorly Water-Soluble Drug Based on a Novel UV Imaging System.

    Science.gov (United States)

    Lu, Yan; Li, Mingzhong

    2016-01-01

    The solubility and diffusion coefficient are two of the most important physicochemical properties of a drug compound. In practice, both have been measured separately, which is time consuming. This work utilizes a novel technique of UV imaging to determine the solubility and diffusion coefficients of poorly water-soluble drugs simultaneously. A 2-step optimal method is proposed to determine the solubility and diffusion coefficients of a poorly water-soluble pharmaceutical substance based on the Fick's second law of diffusion and UV imaging measurements. Experimental results demonstrate that the proposed method can be used to determine the solubility and diffusion coefficients of a drug with reasonable accuracy, indicating that UV imaging may provide a new opportunity to accurately measure the solubility and diffusion coefficients of a poorly water-soluble drug simultaneously and rapidly. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  5. Rapid and Efficient Self-Assembly of Au@ZnO Core-Shell Nanoparticle Arrays with an Enhanced and Tunable Plasmonic Absorption for Photoelectrochemical Hydrogen Generation.

    Science.gov (United States)

    Sun, Yiqiang; Xu, Bo; Shen, Qi; Hang, Lifeng; Men, Dandan; Zhang, Tao; Li, Huilin; Li, Cuncheng; Li, Yue

    2017-09-20

    High-quality Au@ZnO core-shell nanoparticle (NP) array films were easily and efficiently fabricated through an air/water interfacial self-assembly. These materials have remarkable visible light absorption capacity and fascinating performance in photoelectrochemical (PEC) water splitting with a photocurrent density of ∼3.08 mA/cm2 at 0.4 V, which is superior to most ZnO-based photoelectrodes in studies. Additionally, the interesting PEC performance could be effectively adjusted by altering the thickness of the ZnO shell and/or the layer number of the array films. Results indicated that the bilayer film based on Au@ZnO NPs with 25 nm shell thickness displayed optimal behavior. The remarkable PEC capability could be ascribed to the enhanced light-harvesting ability of the Au@ZnO structured NPs by the SPR effect and the optimum film thickness. This work demonstrates a desirable paradigm for preparing photoelectrodes based on the synergistic effect of plasmatic NPs as the core and a visible optical absorbent and semiconductor as the shell. Moreover, this work provides a new approach for fabricating optoelectronic anode thin film devices through a self-assembly method.

  6. RAPID AND SENSITIVE DETERMINATION OF PALLADIUM USING HOMOGENEOUS LIQUID-LIQUID MICROEXTRACTION VIA FLOTATION ASSISTANCE FOLLOWED BY GRAPHITE FURNACE ATOMIC ABSORPTION SPECTROMETRY

    Directory of Open Access Journals (Sweden)

    Mohammad Rezaee

    2015-05-01

    Full Text Available A method for the determination of trace amounts of palladium was developed using homogeneous liquid-liquid microextraction via flotation assistance (HLLME-FA followed by graphite furnace atomic absorption spectrometry (GFAAS. Ammonium pyrrolidine dithiocarbamate (APDC was used as a complexing agent. This was applied to determine palladium in three types of water samples. In this study, a special extraction cell was designed to facilitate collection of the low-density solvent extraction. No centrifugation was required in this procedure. The water sample solution was added to the extraction cell which contained an appropriate mixture of extraction and homogeneous solvents. By using air flotation, the organic solvent was collected at the conical part of the designed cell. Parameters affecting extraction efficiency were investigated and optimized. Under the optimum conditions, the calibration graph was linear in the range of 1.0-200 µg L-1 with a limit of detection of 0.3 µg L-1. The performance of the method was evaluated for the extraction and determination of palladium in water samples and satisfactory results were obtained. In order to verify the accuracy of the approach, the standard addition method was applied for the determination of palladium in spiked synthetic samples and satisfactory results were obtained.

  7. The use of tunable diode laser absorption spectroscopy for rapid measurements of the delta13C of animal breath for physiological and ecological studies.

    Science.gov (United States)

    Engel, Sophia; Lease, Hilary M; McDowell, Nate G; Corbett, Alyssa H; Wolf, Blair O

    2009-05-01

    In this study we introduce the use of tunable diode laser absorption spectroscopy (TDLAS) as a technique for making measurements of the delta13C of animal 'breath' in near real time. The carbon isotope ratios (delta13C) of breath CO2 trace the carbon source of the materials being metabolized, which can provide insight into the use of specific food resources, e.g. those derived from plants using C3 versus C4 or CAM photosynthetic pathways. For physiological studies, labeled substrates and breath analyses provide direct evidence of specific physiological (e.g. fermentative digestion) or enzymatic (e.g. sucrase activity) processes. Although potentially very informative, this approach has rarely been taken in animal physiological or ecological research. In this study we quantify the utilization of different plant resources (photosynthetic types--C3 or C4) in arthropod herbivores by measuring the delta13C of their 'breath' and comparing it with bulk tissue values. We show that breath delta13C values are highly correlated with bulk tissues and for insect herbivores reflect their dietary guild, in our case C3-specialists, C4-specialists, or generalists. TDLAS has a number of advantages that will make it an important tool for physiologists, ecologists and behaviorists: it is non-invasive, fast, very sensitive, accurate, works on animals of a wide range of body sizes, per-sample costs are small, and it is potentially field-deployable. Copyright (c) 2009 John Wiley & Sons, Ltd.

  8. Rapid confirmatory analysis of non-steroidal anti-inflammatory drugs in bovine milk by rapid resolution liquid chromatography tandem mass spectrometry.

    Science.gov (United States)

    Dowling, Geraldine; Gallo, Pasquale; Malone, Edward; Regan, Liam

    2009-11-13

    A rapid method has been developed to analyse carprofen (CPF), diclofenac (DCF), mefenamic acid (MFN), niflumic acid (NIFLU), naproxen (NAP), oxyphenylbutazone (OXYPHEN), phenylbutazone (PBZ) and suxibuzone (SUXI) residues in bovine milk. Milk samples are extracted with acetonitrile and sample extracts were purified on Evolute ABN solid phase extraction cartridges. Aliquots were analysed by rapid resolution liquid chromatography tandem mass spectrometry (RRLC-MS/MS) with a runtime of 6.5 min. The method was validated in bovine milk, according to the criteria defined in Commission Decision 2002/657/EC. CCalpha values of 0.46, 1.08, 0.92, 1.26, 1.29, 2.12, 0.55 and 2.86 ng mL(-1) were determined for CPF, DCF, MFN, NIFLU, NAP, OXYPHEN, PBZ and SUXI, respectively. CCbeta values of 0.79, 1.85, 1.56, 2.15, 2.19, 3.62, 0.94 and 4.87 ng mL(-1) were determined for CPF, DCF, MFN, NIFLU, NAP, OXYPHEN, PBZ and SUXI, respectively. The measurement uncertainty of the method was estimated at 9, 28, 28, 45, 46, 45, 10 and 39% for CPF, DCF, MFN, NIFLU, NAP, OXYPHEN, PBZ and SUXI. Fortifying bovine milk samples (n=18) in three separate assays, show the accuracy of the method to be between 82 and 108%. The precision of the method, expressed as RSD values for the within-lab reproducibility at the three levels of fortification (5, 7.5 and 10 ng mL(-1)) was less than 16%, respectively. The advantage of the method is that low ng mL(-1) levels can be detected and quantitatively confirmed rapidly in milk and that 3 batches of samples can be analysed within a single day using RRLC-MS/MS with a runtime of 6.5 min.

  9. Model-Based Analysis of Biopharmaceutic Experiments To Improve Mechanistic Oral Absorption Modeling: An Integrated in Vitro in Vivo Extrapolation Perspective Using Ketoconazole as a Model Drug.

    Science.gov (United States)

    Pathak, Shriram M; Ruff, Aaron; Kostewicz, Edmund S; Patel, Nikunjkumar; Turner, David B; Jamei, Masoud

    2017-12-04

    KTZ for 200, 300, and 400 mg doses. These results demonstrate that IVIV_E applied to biopharmaceutical experiments can be used to understand and build confidence in the quality of the input parameters and mechanistic models used for mechanistic oral absorption simulations in vivo, thereby improving the prediction performance of PBPK models. Moreover, this approach can inform the selection and design of in vitro experiments, potentially eliminating redundant experiments and thus helping to reduce the cost and time of drug product development.

  10. Fully validated method for rapid and simultaneous measurement of six antiepileptic drugs in serum and plasma using ultra-performance liquid chromatography-electrospray ionization tandem mass spectrometry.

    Science.gov (United States)

    Kuhn, Joachim; Knabbe, Cornelius

    2013-06-15

    Therapeutic drug monitoring (TDM) may be very useful in the clinical management of antiepileptic drug therapy for multiple reasons, such as individual variability, metabolism, genetic factors or drug-drug or drug-food interactions. In addition, TDM is helpful to study the variation in pharmacokinetics that occurs between individuals. Here, we describe a rapid assay using ultra-performance liquid chromatography-electrospray ionization tandem mass spectrometry to measure the antiepileptic drugs lacosamide, lamotrigine, levetiracetam, primidone, topiramate, and zonisamide. After the addition of internal standards (ISs) and protein precipitation of serum or plasma, 1 μl of sample was separated on a 2.1×50 mm reverse phase column (Waters, Acquity UPLC BEH Phenyl, 1.7 μm). Analytes were then ionized and detected by electrospray ionization mass spectrometry with multiple reaction monitoring. Runtime was 2.5 min per injection. Matrix effects were investigated by systematical ion suppression and in-source fragmentation experiments. The calibration curves of the 6 antiepileptic drugs were linear over the working range between 0.05 and 50 mg/L (r>0.99). The limit of detection (LOD) was measured in the assay. The intraassay and interassay coefficients of variation for all compounds were 1.0 mg/L). Mean recoveries were between 87.8 and 98.6% for all drugs. There were no significant ion suppressions detected at the elution times of the analytes. The mean differences between serum and heparinized plasma values were less than 6% for the 6 antiepileptic drugs. All drugs were stable in serum at -20°C, 4°C, and even at RT for at least 1 month. In summary, a specific and sensitive stable isotope dilution UPLC-MS/MS method was developed and validated for routine clinical monitoring of lacosamide, lamotrigine, levetiracetam, primidone, topiramate, and zonisamide. Copyright © 2013 Elsevier B.V. All rights reserved.

  11. Rapid determination of yunaconitine and related alkaloids in aconites and aconite-containing drugs by ultra high-performance liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Song, Long; Zhang, Hong; Liu, Xin; Zhao, Zhi-Li; Chen, Shi-Lin; Wang, Zheng-Tao; Xu, Hong-Xi

    2012-12-01

    Yunaconitine (YAC) is a toxic aconite alkaloid that is considered to be a hidden aconite poison since it is frequently found in body fluids from aconite poisoning patients, but has not been well studied in commonly used herbal drugs. In this paper, a rapid and sensitive ultra high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) detection combined with microwave-assisted extraction (MAE) was developed for high throughput simultaneous determination of YAC and six other toxic aconite alkaloids in 31 samples of crude, processed aconites and aconite-containing drugs. The optimized method showed excellent linearity, precision, accuracy and recovery for all target compounds with short run time. YAC was detected in some samples with contents from 0.015 to 10.41 mg/g. This is the first report on the determination of YAC in Radix Aconiti, Radix Aconiti Kusnezoffii and aconite-containing drugs. This newly developed method facilitates the rapid screening of YAC and related toxic aconite alkaloids and allows YAC to be used as a chemical marker for the quality control of aconites and aconite-containing drugs. Copyright © 2012 John Wiley & Sons, Ltd.

  12. A quantitative high-resolution genetic profile rapidly identifies sequence determinants of hepatitis C viral fitness and drug sensitivity.

    Directory of Open Access Journals (Sweden)

    Hangfei Qi

    2014-04-01

    Full Text Available Widely used chemical genetic screens have greatly facilitated the identification of many antiviral agents. However, the regions of interaction and inhibitory mechanisms of many therapeutic candidates have yet to be elucidated. Previous chemical screens identified Daclatasvir (BMS-790052 as a potent nonstructural protein 5A (NS5A inhibitor for Hepatitis C virus (HCV infection with an unclear inhibitory mechanism. Here we have developed a quantitative high-resolution genetic (qHRG approach to systematically map the drug-protein interactions between Daclatasvir and NS5A and profile genetic barriers to Daclatasvir resistance. We implemented saturation mutagenesis in combination with next-generation sequencing technology to systematically quantify the effect of every possible amino acid substitution in the drug-targeted region (domain IA of NS5A on replication fitness and sensitivity to Daclatasvir. This enabled determination of the residues governing drug-protein interactions. The relative fitness and drug sensitivity profiles also provide a comprehensive reference of the genetic barriers for all possible single amino acid changes during viral evolution, which we utilized to predict clinical outcomes using mathematical models. We envision that this high-resolution profiling methodology will be useful for next-generation drug development to select drugs with higher fitness costs to resistance, and also for informing the rational use of drugs based on viral variant spectra from patients.

  13. Rapid in situ detection of street samples of drugs of abuse on textile substrates using microRaman spectroscopy

    Science.gov (United States)

    Ali, Esam M. A.; Edwards, Howell G. M.; Scowen, Ian J.

    2011-10-01

    Trace amounts of street samples of cocaine hydrochloride and N-methyl-3,4-methylenedioxy-amphetamine (MDMA) on natural and synthetic textiles were successfully detected in situ using confocal Raman microscopy. The presence of some excipient bands in the spectra of the drugs did not prevent the unambiguous identification of the drugs. Raman spectra of the drugs were readily obtained without significant interference from the fibre substrates. Interfering bands arising from the fibre natural or synthetic polymer structure and/or dye molecules did not overlap with the characteristic Raman bands of the drugs. If needed, interfering bands could be successfully removed by spectral subtraction. Also, Raman spectra could be acquired from drug particles trapped between the fibres of highly fluorescent textile specimens. The total acquisition time of the spectra of the drug particles was 90 s accomplished non-destructively and without detachment from their substrates. Sample preparation was not required and spectra of the drugs could be obtained non-invasively preserving the integrity of the evidential material for further analysis.

  14. Magnetically optimized SERS assay for rapid detection of trace drug-related biomarkers in saliva and fingerprints.

    Science.gov (United States)

    Yang, Tianxi; Guo, Xiaoyu; Wang, Hui; Fu, Shuyue; Wen, Ying; Yang, Haifeng

    2015-06-15

    New developments in the fields of human healthcare and social security call for the exploration of an easy and on-field method to detect drug-related biomarkers. In this paper, Au nanoparticles dotted magnetic nanocomposites (AMN) modified with inositol hexakisphosphate (IP6) were used as surface-enhanced Raman scattering (SERS) substrate to quickly monitor trace drug-related biomarkers in saliva and to on-site screen a trace drug biomarker in fingerprints. Due to inducing with an external magnet, such substrate presented a huge SERS activity, which has met the sensitivity requirement for assay to detect the drug biomarkers in saliva from the U.S. Substance Abuse and Mental Health Services Administration, and also the limit of detection for drug biomarker in fingerprint reached 100 nM. In addition, this AMN-based SERS assay was successfully conducted using a portable Raman spectrometer, which could be used to on-site and accurately differentiate between the smokers and drug addicts in near future. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. A multi-site validation in India of the line probe assay for the rapid diagnosis of multi-drug resistant tuberculosis directly from sputum specimens.

    Science.gov (United States)

    Raizada, Neeraj; Sachdeva, K S; Chauhan, D S; Malhotra, Bharti; Reddy, Kishore; Dave, P V; Mundade, Yamuna; Patel, Pranav; Ramachandran, Ranjani; Das, Ram; Solanki, Rajesh; Wares, Douglas Fraser; Sahu, Suvanand; O'Brien, Rick; Paramasivan, C N; Dewan, Puneet K

    2014-01-01

    Rifampicin (R) and isoniazid (H) are key first-line anti-tuberculosis drugs. Failure to detect resistance to these two drugs early results in treatment failure and poor clinical outcomes. The study purpose was to validate the use of the GenoType MTBDRplus line probe assay (LPA) to detect resistance to R and H in Mycobacterium tuberculosis strains directly from smear-positive sputum samples in India. Smear positive sputum specimens from 320 patients were subjected to LPA and results compared against those from conventional Lowenstein Jensen (LJ) culture and drug susceptibility testing (C&DST). All specimens with discordant R DST results were subjected to either sequencing of the rpoB gene and/or repeat DST on liquid culture (MGIT 960) at a National Reference Laboratory. Significantly higher proportion of interpretable results were observed with LPA compared to LJ C&DST (94% vs. 80%, p-value turnaround testing time, including specimen transportation time, on LPA was 11 days as compared with 89 days for LJ C&DST. LPA proved highly accurate in the rapid detection of R resistance. The reduction in time to diagnosis may potentially enable earlier commencement of the appropriate drug therapy, leading to some reduction of transmission of drug-resistant strains.

  16. Preparation of multilocation reduction-sensitive core crosslinked folate-PEG-coated micelles for rapid release of doxorubicin and tariquidar to overcome drug resistance

    Science.gov (United States)

    Yi, Xiaoqing; Zhao, Dan; Zhang, Quan; Xu, Jiaqi; Yuan, Gongdao; Zhuo, Renxi; Li, Feng

    2017-02-01

    Herein, we prepared folate-targeting core crosslinked polymeric micelles (CCL/FA) containing multiple disulfide bonds located at the interface and core of the micelles to co-deliver doxorubicin (DOX) and the P-glycoprotein (P-gp) inhibitor tariquidar (TQR) for reversing drug resistance. The stability and redox-responsive behavior of the CCL/FA micelles was evaluated through the changes in morphology, molecular weight and hydrodynamic size. On the one hand, the micelles possessed good stability, which led to the suppression of drug release from the CCL micelles in the physiological environment. On the other hand, under reductive conditions, the CCL micelles collapsed rapidly and accelerated drug release markedly. In vitro cytotoxicity measurements, combined with confocal laser scanning microscopy (CLSM) and flow cytometry, confirmed that the dual-drug-loaded micelles exhibited obviously higher cytotoxicity to MCF-7/ADR-resistant cells than free DOX · HCl, single-drug loaded CCL micelles and nontargeted CCL micelles. The results imply that co-delivering DOX and TQR by CCL/FA micelles may be a promising way of overcoming multidrug resistance in tumor treatments.

  17. Willingness-to-pay for a rapid malaria diagnostic test and artemisinin-based combination therapy from private drug shops in Mukono District, Uganda.

    Science.gov (United States)

    Hansen, Kristian Schultz; Pedrazzoli, Debora; Mbonye, Anthony; Clarke, Sian; Cundill, Bonnie; Magnussen, Pascal; Yeung, Shunmay

    2013-03-01

    In Uganda, as in many parts of Africa, the majority of the population seek treatment for malaria in drug shops as their first point of care; however, parasitological diagnosis is not usually offered in these outlets. Rapid diagnostic tests (RDTs) for malaria have attracted interest in recent years as a tool to improve malaria diagnosis, since they have proved accurate and easy to perform with minimal training. Although RDTs could feasibly be performed by drug shop vendors, it is not known how much customers would be willing to pay for an RDT if offered in these settings. We conducted a contingent valuation survey among drug shop customers in Mukono District, Uganda. Exit interviews were undertaken with customers aged 15 years and above after leaving a drug shop having purchased an antimalarial and/or paracetamol. The bidding game technique was used to elicit the willingness-to-pay (WTP) for an RDT and a course of artemisinin-based combination therapy (ACT) with and without RDT confirmation. Factors associated with WTP were investigated using linear regression. The geometric mean WTP for an RDT was US$0.53, US$1.82 for a course of ACT and US$2.05 for a course of ACT after a positive RDT. Factors strongly associated with a higher WTP for these commodities included having a higher socio-economic status, no fever/malaria in the household in the past 2 weeks and if a malaria diagnosis had been obtained from a qualified health worker prior to visiting the drug shop. The findings further suggest that the WTP for an RDT and a course of ACT among drug shop customers is considerably lower than prevailing and estimated end-user prices for these commodities. Increasing the uptake of ACTs in drug shops and restricting the sale of ACTs to parasitologically confirmed malaria will therefore require additional measures.

  18. Analytical strategy for rapid identification and quantification of lubricant additives in mineral oil by high-performance thin-layer chromatography with UV absorption and fluorescence detection combined with mass spectrometry and infrared spectroscopy.

    Science.gov (United States)

    Dytkiewitz, Elisabeth; Morlock, Gertrud E

    2008-01-01

    A simple strategy for identification and quantification of lubricant additives in mineral oil was demonstrated by high-performance thin-layer chromatography with UV absorption and fluorescence detection using various coupling options, e.g., with attenuated total reflectance infrared (ATR-IR) spectroscopy, Fourier transform infrared (FTIR) spectroscopy, electrospray ionization mass spectrometry (ESI-MS), and direct analysis in real-time mass spectrometry (DART-MS). For the additives zinc bis(O,O'-diisobutyl dithiophosphate), zinc bis(O,O'-didodecyl dithiophosphate), and Anglamol 99, 2 chromatographic systems were developed, i.e., a reversed-phase (RP) system on RP2 plates using an acetonitrile-based mobile phase and a normal-phase system on silica gel 60 plates using a toluene-based gradient. Densitometry was performed by absorption measurement at 220 nm. Repeatabilities (relative standard deviation, n = 6) between 2.2 and 5.5% and correlation coefficients >0.9973 were highly satisfactory for the analysis of these additives in the mineral oil. Primuline reagent was used to improve the detection limit of the lipophilic additives by a factor of 2, followed by fluorescence measurement at UV 366/>400 nm. For rapid identification by ATR-IR and FTIR, the respective additive zones on the plate were online extracted by an interface called ChromeXtract, concentrated, and directly applied for measurements in the wave number range of 4000-400 cm(-1). Identification was confirmed by online ESI-MS within a minute using ChromeXtract and by DART-MS within seconds.

  19. Tailor-Made pH-Responsive Poly(choline phosphate) Prodrug as a Drug Delivery System for Rapid Cellular Internalization.

    Science.gov (United States)

    Wang, Wenliang; Wang, Bo; Ma, Xiaojing; Liu, Sanrong; Shang, Xudong; Yu, Xifei

    2016-06-13

    Rapid cellular uptake and efficient drug release in tumor cells are two of the major challenges for cancer therapy. Herein, we designed and synthesized a novel pH-responsive polymer-drug conjugate system poly(2-(methacryloyloxy)ethyl choline phosphate)-b-poly(2-methoxy-2-oxoethyl methacrylate-hydrazide-doxorubicin) (PCP-Dox) to overcome these two challenges simultaneously. It has been proved that PCP-Dox can be easily and rapidly internalized by various cancer cells due to the strong interaction between multivalent choline phosphate (CP) groups and cell membranes. Furthermore, Dox, linked to the polymer carrier via acid-labile hydrazone bond, can be released from carriers due to the increased acidity in lysosome/endosome (pH 5.0-5.5) after the polymer prodrug was internalized into the cancer cells. The cell viability assay demonstrated that this novel polymer prodrug has shown enhanced cytotoxicity in various cancer cells, indicating its great potential as a new drug delivery system for cancer therapy.

  20. Use of peak decay analysis and affinity microcolumns containing silica monoliths for rapid determination of drug-protein dissociation rates.

    Science.gov (United States)

    Yoo, Michelle J; Hage, David S

    2011-04-15

    This report examined the use of silica monoliths in affinity microcolumns containing human serum albumin (HSA) to measure the dissociation rates for various drugs from this protein. Immobilized HSA and control monolith columns with dimensions of 1 mm × 4.6 mm i.d. were prepared for this work and used with a noncompetitive peak decay method. Several drugs known to bind HSA were examined, such as warfarin, diazepam, imipramine, acetohexamide, and tolbutamide. Items that were studied and optimized in this method included the sample volume, sample concentration, and elution flow rate. It was found that flow rates up to 10 mL/min could be used in this approach. Work with HSA silica monoliths at these high flow rates made it possible to provide dissociation rate constants for drugs such as warfarin in less than 40s. The dissociation rate constants that were measured gave good agreement with values reported in the literature or that had been obtained with other solutes that had similar binding affinities for HSA. This approach is a general one that should be useful in examining the dissociation of other drugs from HSA and in providing a high-throughput method for screening drug-protein interactions. Copyright © 2010 Elsevier B.V. All rights reserved.

  1. THE ABSORPTION OF ADRENALIN AFTER INTRATRACHEAL INJECTION.

    Science.gov (United States)

    Auer, J; Gates, F L

    1916-06-01

    occurs also through the lymphatics. By far the larger proportion of the absorbed material will thus be rapidly delivered to the left auricle and then to the left ventricle. At each succeeding systole, as long as absorption continues, a fraction of the drug will be driven into the coronary arteries and be able to affect the musculature of the cardiac pump. This fact ought to render the procedure of intratracheal injection a valuable method when it becomes imperative to stimulate a suddenly failing heart as promptly as possible by drugs of the digitalis group. Intratracheal injection is perhaps better under the conditions mentioned than the intravenous route, for the surface veins cannot always be entered with promptness and certainty even under fairly normal conditions, and in cases of cardiac weakness the difficulties will be measurably increased, while an intratracheal injection can be carried out with ease. Moreover, it is legitimate to expect that some absorption will take place from the lung alveoli as long as the heart-lung circulation persists, no matter how feebly, and that thus some of the drug will reach the heart to act on this structure itself more promptly perhaps than when the drug is administered successfully through surface veins. As far as the intramuscular route is concerned, we have shown that the intratracheal injection of adrenalin gives prompt though diminished absorption at a time when double the dose intramuscularly exerts no blood pressure effect whatever. The technical difficulties of giving an intratracheal injection in animals are slight. Tracheotomy as practised by us in the present series of experiments is not necessary, for the injection may be given into the intact trachea without exposure of the trachea. The hypodermic needle is inserted through the skin about 1 cm. below the larynx in a slanting caudad direction; the entrance of the needle into the trachea is readily felt. The injection should not be so rapid that the injected solution

  2. The protease inhibitors ritonavir and saquinavir influence lipid metabolism: a pig model for the rapid evaluation of new drugs

    DEFF Research Database (Denmark)

    Petersen, E.; Mu, Huiling; Porsgaard, Trine

    2010-01-01

    Background: Studies of the effects of antiretroviral drugs on lipid metabolism are limited by the availability of suitable models. We have thus developed an animal model utilising Gottingen mini-pigs. The normal lipid metabolism of mini-pigs closely reflects that of humans and they are expected t...

  3. Rapid determination of furosemide in drug and blood plasma of wrestlers by a carboxyl-MWCNT sensor.

    Science.gov (United States)

    Heidarimoghadam, Rashid; Farmany, Abbas

    2016-01-01

    A novel method is developed for the quantification of furosemide in biological fluids. The method is based on the electro-reduction of Zn(II)-furosemide complex at carboxyl-MWCNT modified glassy carbon electrode. It is shown that, in Britton-Robinson buffer (pH5.7) the reduction peak of Zn(II)-furosemide complex formed at -1.0 V (versus, Ag/AgCl). The increment of current signal obtained from the reduction peak current of the Zn(II)-furosemide complex was rectilinear with furosemide concentration in the range of 0.03 to 140.0 μg ml(-1), with a detection limit of 0.007 μg ml(-1). The drug recovery ranged between 97.8% and 100.8% and the mean drug recovery was 98.89%. The accuracies (relative error% and RSD%) were less than 15% and are acceptable according to the US FDA guideline for bioanalytical method validation. The sensor was used for quantification of furosemide in drug and biological fluid samples. The data of drug analysis were compared with the standard method. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Narrative absorption

    DEFF Research Database (Denmark)

    Narrative Absorption brings together research from the social sciences and Humanities to solve a number of mysteries: Most of us will have had those moments, of being totally absorbed in a book, a movie, or computer game. Typically we do not have any idea about how we ended up in such a state. No...

  5. Willingness-to-pay for a rapid malaria diagnostic test and artemisinin-based combination therapy from private drug shops in Mukono district, Uganda

    DEFF Research Database (Denmark)

    Hansen, Kristian Schultz; Pedrazzoli, Debora; Mbonye, Anthony

    2013-01-01

    In Uganda, as in many parts of Africa, the majority of the population seek treatment for malaria in drug shops as their first point of care; however, parasitological diagnosis is not usually offered in these outlets. Rapid diagnostic tests (RDTs) for malaria have attracted interest in recent years...... and a course of artemisinin-based combination therapy (ACT) with and without RDT confirmation. Factors associated with WTP were investigated using linear regression. The geometric mean WTP for an RDT was US$0.53, US$1.82 for a course of ACT and US$2.05 for a course of ACT after a positive RDT. Factors strongly...

  6. A rapid and low-cost microscopic observation drug susceptibility assay for detecting TB and MDR-TB among individuals infected by HIV in South India

    Directory of Open Access Journals (Sweden)

    S Solomon

    2013-01-01

    Full Text Available Background: The converging epidemics of HIV and tuberculosis (TB pose one of the greatest public health challenges of our time. Rapid diagnosis of TB is essential in view of its infectious nature, high burden of cases, and emergence of drug resistance. Objective: The purpose of this present study was to evaluate the feasibility of implementing the microscopic observation drug susceptibility (MODS assay, a novel assay for the diagnosis of TB and multi-drug-resistant tuberculosis (MDR-TB directly from sputum specimens, in the Indian setting. Materials and Methods: This study involved a cross-sectional, blinded assessment of the MODS assay on 1036 suspected cases of pulmonary TB in HIV-positive and HIV-negative patients against the radiometric method, BD-BACTEC TB 460 system. Results: Overall, the sensitivity, specificity, positive predictive value, and negative predictive value of the MODS assay in detecting MTB among TB suspected patients were 89.1%, 99.1%, 94.2%, 95.8%, respectively. In addition, in the diagnosis of drug-resistant TB, the MODS assay was 84.2% sensitive for those specimens reporting MDR, 87% sensitivity for those specimens reporting INH mono-resistance, and 100% sensitive for specimens reporting RIF mono-resistance. The median time to detection of TB in the MODS assay versus BACTEC was 9 versus 21 days (P < 0.001. Conclusion: Costing 5 to 10 times lesser than the automated culture methods, the MODS assay has the potential clinical utility as a simple and rapid method. It could be effectively used as an alternative method for diagnosing TB and detection of MDR-TB in a timely and affordable way in resource-limited settings.

  7. Rapid BAL Variability: Re-Emerging Absorption

    Directory of Open Access Journals (Sweden)

    Damla Erakuman

    2017-11-01

    Full Text Available We study BAL variations of SDSS J141955.28+522741.4 utilizing 32 epochs of spectroscopic observations from SDSS. We identify three individual BAL troughs for C iv and one BAL trough for Si iv. The deepest C iv BAL trough shows significant EW variations in timescales of a few 10 h. The fast component of the deepest C iv BAL presents disappearance and re-emergence preserving its initial velocity range and profile. All identified BAL troughs show coordinated variations supporting that the possible mechanism behind variations are the ionization level changes of the absorbing gas.

  8. Rapid analysis of the essential oils from dried Illicium verum Hook. f. and Zingiber officinale Rosc. by improved solvent-free microwave extraction with three types of microwave-absorption medium.

    Science.gov (United States)

    Wang, Ziming; Wang, Lu; Li, Tiechun; Zhou, Xin; Ding, Lan; Yu, Yong; Yu, Aimin; Zhang, Hanqi

    2006-11-01

    A new method of extracting essential oils from dried plant materials has been studied. By adding a microwave-absorption medium (MAM) to a reactor, solvent-free microwave extraction (SFME) was improved and can be used to extract essential oils from dried plant material without pretreatment. With a microwave irradiation power of 85 W it took only approximately 30 min to extract the essential oils completely. The whole extraction process is simple, rapid, and economical. Three types of MAM, iron carbonyl powder (ICP), graphite powder (GP), and activated carbon powder (ACP), and two types of dried plant material, Illicium verum Hook. f. and Zingiber officinale Rosc., were studied. The results were compared with those obtained by use of conventional SFME, microwave-assisted hydrodistillation (MAHD), and conventional hydrodistillation (HD), and the conclusion drawn was that improved SFME was a feasible means of extracting essential oils from dried plant materials, because there were few differences between the composition of the essential oils extracted by improved SFME and by the other methods.

  9. Rapid determination of vial heat transfer parameters using tunable diode laser absorption spectroscopy (TDLAS) in response to step-changes in pressure set-point during freeze-drying.

    Science.gov (United States)

    Kuu, Wei Y; Nail, Steven L; Sacha, Gregory

    2009-03-01

    The purpose of this study was to perform a rapid determination of vial heat transfer parameters, that is, the contact parameter K(cs) and the separation distance l(v), using the sublimation rate profiles measured by tunable diode laser absorption spectroscopy (TDLAS). In this study, each size of vial was filled with pure water followed by a freeze-drying cycle using a LyoStar II dryer (FTS Systems) with step-changes of the chamber pressure set-point at to 25, 50, 100, 200, 300, and 400 mTorr. K(cs) was independently determined by nonlinear parameter estimation using the sublimation rates measured at the pressure set-point of 25 mTorr. After obtaining K(cs), the l(v) value for each vial size was determined by nonlinear parameter estimation using the pooled sublimation rate profiles obtained at 25 to 400 mTorr. The vial heat transfer coefficient K(v), as a function of the chamber pressure, was readily calculated, using the obtained K(cs) and l(v) values. It is interesting to note the significant difference in K(v) of two similar types of 10 mL Schott tubing vials, primary due to the geometry of the vial-bottom, as demonstrated by the images of the contact areas of the vial-bottom. (c) 2008 Wiley-Liss, Inc. and the American Pharmacists Association

  10. Rapid generation of drug-resistance alleles at endogenous loci using CRISPR-Cas9 indel mutagenesis.

    Directory of Open Access Journals (Sweden)

    Jonathan J Ipsaro

    Full Text Available Genetic alterations conferring resistance to the effects of chemical inhibitors are valuable tools for validating on-target effects in cells. Unfortunately, for many therapeutic targets such alleles are not available. To address this issue, we evaluated whether CRISPR-Cas9-mediated insertion/deletion (indel mutagenesis can produce drug-resistance alleles at endogenous loci. This method takes advantage of the heterogeneous in-frame alleles produced following Cas9-mediated DNA cleavage, which we show can generate rare alleles that confer resistance to the growth-arrest caused by chemical inhibitors. We used this approach to identify novel resistance alleles of two lysine methyltransferases, DOT1L and EZH2, which are each essential for the growth of MLL-fusion leukemia cells. We biochemically characterized the DOT1L mutation, showing that it is significantly more active than the wild-type enzyme. These findings validate the on-target anti-leukemia activities of existing DOT1L and EZH2 inhibitors and reveal a simple method for deriving drug-resistance alleles for novel targets, which may have utility during early stages of drug development.

  11. Combining in vitro and in silico methods for better prediction of surfactant effects on the absorption of poorly water soluble drugs-a fenofibrate case example

    DEFF Research Database (Denmark)

    Berthelsen, Ragna; Sjögren, Erik; Jacobsen, Jette

    2014-01-01

    performed using the GI-Sim absorption model. All simulation runs were performed twice adopting either a total small intestinal volume of 533mL or 105mL, in order to examine the implication of free luminal water volumes for the in silico predictions. For the tested formulations, the use of a small...

  12. A multi-site validation in India of the line probe assay for the rapid diagnosis of multi-drug resistant tuberculosis directly from sputum specimens.

    Directory of Open Access Journals (Sweden)

    Neeraj Raizada

    Full Text Available Rifampicin (R and isoniazid (H are key first-line anti-tuberculosis drugs. Failure to detect resistance to these two drugs early results in treatment failure and poor clinical outcomes. The study purpose was to validate the use of the GenoType MTBDRplus line probe assay (LPA to detect resistance to R and H in Mycobacterium tuberculosis strains directly from smear-positive sputum samples in India.Smear positive sputum specimens from 320 patients were subjected to LPA and results compared against those from conventional Lowenstein Jensen (LJ culture and drug susceptibility testing (C&DST. All specimens with discordant R DST results were subjected to either sequencing of the rpoB gene and/or repeat DST on liquid culture (MGIT 960 at a National Reference Laboratory.Significantly higher proportion of interpretable results were observed with LPA compared to LJ C&DST (94% vs. 80%, p-value <0.01. A total of 248 patients had both LJ and LPA DST results available; 232 (93.5% had concordant R DST results. Among the 16 discordant R DST results, 13 (81% were resolved in agreement with LPA results. Final LPA performance characteristics were sensitivity 96% (CI: 90%-98%, specificity 99% (CI: 95%-99%, positive predictive value 99% (CI: 95%-99%, and negative predictive value 95% (CI: 89%-98%. The median turnaround testing time, including specimen transportation time, on LPA was 11 days as compared with 89 days for LJ C&DST.LPA proved highly accurate in the rapid detection of R resistance. The reduction in time to diagnosis may potentially enable earlier commencement of the appropriate drug therapy, leading to some reduction of transmission of drug-resistant strains.

  13. Multicentre laboratory validation of the colorimetric redox indicator (CRI) assay for the rapid detection of extensively drug-resistant (XDR) Mycobacterium tuberculosis.

    Science.gov (United States)

    Martin, Anandi; Paasch, Fabienne; Docx, Sven; Fissette, Krista; Imperiale, Belen; Ribón, Wellman; González, Liliana Andrea; Werngren, Jim; Engström, Anna; Skenders, Girts; Juréen, Pontus; Hoffner, Sven; Del Portillo, Patricia; Morcillo, Nora; Palomino, Juan Carlos

    2011-04-01

    To perform a multicentre study to evaluate the performance of the colorimetric redox indicator (CRI) assay and to establish the MICs and critical concentrations of rifampicin, isoniazid, ofloxacin, kanamycin and capreomycin. The study was carried out in two phases. Phase I determined the MIC of each drug. Phase II established critical concentrations for the five drugs tested by the CRI assay compared with the conventional proportion method. Phase I: a strain was considered resistant by the CRI assay if the MIC was ≥0.5 mg/L for rifampicin, ≥0.25 mg/L for isoniazid, ≥4.0 mg/L for ofloxacin and ≥5.0 mg/L for kanamycin and capreomycin. Sensitivity was 99.1% for isoniazid and 100% for the other drugs and specificity was 97.9% for capreomycin and 100% for the other drugs. Phase II: the critical concentration was 0.5 mg/L for rifampicin, 0.25 mg/L for isoniazid, 2.0 mg/L for ofloxacin and 2.5 mg/L for kanamycin and capreomycin giving an overall accuracy of 98.4%, 96.6%, 96.7%, 98.3% and 90%, respectively. Results demonstrate that the CRI assay is an accurate method for the rapid detection of XDR Mycobacterium tuberculosis. The CRI assay is faster than the conventional drug susceptibility testing method using solid medium, has the same turnaround time as the BACTEC MGIT 960 system, but is less expensive, and could be an adequate method for low-income countries.

  14. Novel ultra-rapid freezing particle engineering process for enhancement of dissolution rates of poorly water-soluble drugs.

    Science.gov (United States)

    Overhoff, Kirk A; Engstrom, Josh D; Chen, Bo; Scherzer, Brian D; Milner, Thomas E; Johnston, Keith P; Williams, Robert O

    2007-01-01

    An ultra-rapid freezing (URF) technology has been developed to produce high surface area powders composed of solid solutions of an active pharmaceutical ingredient (API) and a polymer stabilizer. A solution of API and polymer excipient(s) is spread on a cold solid surface to form a thin film that freezes in 50 ms to 1s. This study provides an understanding of how the solvent's physical properties and the thin film geometry influence the freezing rate and consequently the final physico-chemical properties of URF-processed powders. Theoretical calculations of heat transfer rates are shown to be in agreement with infrared images with 10ms resolution. Danazol (DAN)/polyvinylpyrrolidone (PVP) powders, produced from both acetonitrile (ACN) and tert-butanol (T-BUT) as the solvent, were amorphous with high surface areas (approximately 28-30 m2/g) and enhanced dissolution rates. However, differences in surface morphology were observed and attributed to the cooling rate (film thickness) as predicted by the model. Relative to spray-freezing processes that use liquid nitrogen, URF also offers fast heat transfer rates as a result of the intimate contact between the solution and cold solid surface, but without the complexity of cryogen evaporation (Leidenfrost effect). The ability to produce amorphous high surface area powders with submicron primary particles with a simple ultra-rapid freezing process is of practical interest in particle engineering to increase dissolution rates, and ultimately bioavailability.

  15. Rapid wide-scope screening of drugs of abuse, prescription drugs with potential for abuse and their metabolites in influent and effluent urban wastewater by ultrahigh pressure liquid chromatography-quadrupole-time-of-flight-mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Hernandez, Felix, E-mail: felix.hernandez@qfa.uji.es [Research Institute for Pesticides and Water, University Jaume I, Avda. Sos Baynat s/n, E-12071 Castellon (Spain); Bijlsma, Lubertus, E-mail: bijlsma@guest.uji.es [Research Institute for Pesticides and Water, University Jaume I, Avda. Sos Baynat s/n, E-12071 Castellon (Spain); Sancho, Juan V.; Diaz, Ramon; Ibanez, Maria [Research Institute for Pesticides and Water, University Jaume I, Avda. Sos Baynat s/n, E-12071 Castellon (Spain)

    2011-01-17

    This work illustrates the potential of hybrid quadrupole-time-of-flight mass spectrometry (QTOF MS) coupled to ultrahigh pressure liquid chromatography (UHPLC) to investigate the presence of drugs of abuse in wastewater. After solid-phase extraction with Oasis MCX cartridges, seventy-six illicit drugs, prescription drugs with potential for abuse, and metabolites were investigated in the samples by TOF MS using electrospray interface under positive ionization mode, with MS data acquired over an m/z range of 50-1000 Da. For 11 compounds, reference standards were available, and experimental data (e.g., retention time and fragmentation data) could be obtained, facilitating a more confident identification. The use of a QTOF instrument enabled the simultaneous application of two acquisition functions with different collision energies: a low energy (LE) function, where none or poor fragmentation took place, and a high energy (HE) function, where fragmentation in the collision cell was promoted. This approach, known as MS{sup E}, enabled the simultaneous acquisition of full-spectrum accurate mass data of both protonated molecules and fragment ions in a single injection, providing relevant information that facilitates the rapid detection and reliable identification of these emerging contaminants in the sample matrices analyzed. In addition, isomeric compounds, like the opiates, morphine and norcodeine, could be discriminated by their specific fragments observed in HE TOF MS spectra, without the need of reference standards. UHPLC-QTOF MS was proven to be a powerful and efficient technique for rapid wide-scope screening and identification of many relevant drugs in complex matrices, such as influent and effluent urban wastewater.

  16. A microstructural study of sleep instability in drug-naive patients with schizophrenia and healthy controls: sleep spindles, rapid eye movements, and muscle atonia.

    Science.gov (United States)

    Guénolé, Fabian; Chevrier, Elyse; Stip, Emmanuel; Godbout, Roger

    2014-05-01

    This study aimed at characterizing the functional stability of sleep in schizophrenia by quantifying dissociated stages of sleep (DSS), and to explore their correlation with psychopathology. The sleep of 10 first-break, drug-naive young adults with schizophrenia and 10 controls was recorded. Four basic DSS patterns were scored: 1) the transitional EEG-mixed intermediate stage (EMIS); 2) Rapid-eye-movement (REM) sleep without rapid eye movement (RSWR); 3) REM sleep without atonia (RSWA); and 4) non-REM sleep with rapid eye movements. An intermediate sleep (IS) score was calculated by summing EMIS and RSWR scores, and the durations of intra-REM sleep periods IS (IRSPIS) and IS scored "at the expense" of REM sleep (ISERS) were determined. Patients were administered the Brief Psychiatric Rating Scale (BPRS) at the time of recording. Proportions of each DSS variables over total sleep time and proportions of IRSPIS and ISERS over REM sleep duration were compared between patients and controls. Correlation coefficients between DSS variables and BPRS total scores were calculated. The proportion of total DSS did not differ between patients and controls. Among DSS subtypes, RSWA was significantly increased in patients while other comparisons showed no significant differences. Significant positive correlations were found between BPRS scores and proportions of DSS, IS, RSWR, IRSPIS and ISERS over total sleep and REM sleep durations. These results demonstrate the functional instability of REM sleep in first-break, drug naive young adults with schizophrenia and unveil a pattern reminiscent of REM sleep behavior disorder. The significant correlation suggests that schizophrenia and REM sleep share common neuronal control mechanisms. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Optimization of Sample Preparation and Instrumental Parameters for the Rapid Analysis of Drugs of Abuse in Hair samples by MALDI-MS/MS Imaging

    Science.gov (United States)

    Flinders, Bryn; Beasley, Emma; Verlaan, Ricky M.; Cuypers, Eva; Francese, Simona; Bassindale, Tom; Clench, Malcolm R.; Heeren, Ron M. A.

    2017-08-01

    Matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) has been employed to rapidly screen longitudinally sectioned drug user hair samples for cocaine and its metabolites using continuous raster imaging. Optimization of the spatial resolution and raster speed were performed on intact cocaine contaminated hair samples. The optimized settings (100 × 150 μm at 0.24 mm/s) were subsequently used to examine longitudinally sectioned drug user hair samples. The MALDI-MS/MS images showed the distribution of the most abundant cocaine product ion at m/z 182. Using the optimized settings, multiple hair samples obtained from two users were analyzed in approximately 3 h: six times faster than the standard spot-to-spot acquisition method. Quantitation was achieved using longitudinally sectioned control hair samples sprayed with a cocaine dilution series. A multiple reaction monitoring (MRM) experiment was also performed using the `dynamic pixel' imaging method to screen for cocaine and a range of its metabolites, in order to differentiate between contaminated hairs and drug users. Cocaine, benzoylecgonine, and cocaethylene were detectable, in agreement with analyses carried out using the standard LC-MS/MS method. [Figure not available: see fulltext.

  18. Modelos in vitro para determinação da absorção de fármacos e previsão da relação dissolução/absorção In vitro models for the determination of drug absorption and a prediction of dissolution/absorption relationships

    Directory of Open Access Journals (Sweden)

    Jacqueline de Souza

    2007-12-01

    Full Text Available Fármacos contidos em formas farmacêuticas sólidas devem ter adequada solubilidade aquosa e permeabilidade intestinal para serem absorvidos após administração oral. A velocidade e a extensão com as quais um fármaco é absorvido podem variar devido às suas características físico-químicas e fatores relacionados à desintegração e dissolução. Segundo o Sistema de Classificação Biofarmacêutica (SCB, a dissolução e a permeação intestinal do fármaco podem limitar a absorção e, conseqüentemente, a ação terapêutica. Este trabalho objetiva discutir dados da literatura referentes à previsão da relação entre a dissolução de fármacos e sua absorção empregando sistemas in vitro. Para avaliar a permeação in vitro são discutidos modelos com tecidos e segmentos intestinais, vesículas extraídas de membranas e cultura de células. Na literatura existem estudos de permeabilidade utilizando células Caco-2, TC-7, 2/4/A1, MDCK e MDCK-MDR1. As células Caco-2 são extraídas de adenocarcinoma de c��lon humano que, em cultura celular, se diferenciam em enterócitos, podendo ser acopladas a sistemas de dissolução. Estas técnicas representam importante ferramenta para estudos de dissolução/permeação, porém, ainda são limitadas e não conseguem reproduzir adequadamente os mecanismos de transporte ativo.Drugs contained in a solid pharmaceutical form should be adequately water soluble and permeable, into the intestine in order to be effectively absorbed after oral adminis-tration. The speed and extent at which a drug is absorbed can vary due to its physicochemical characteristics and factors related to disintegration and dissolution of the drug. According to Biopharmaceutical Drug System Classification (BSC, the dissolution and the intestinal permeation of a drug can limit the absorption and, consequently, the therapeutic action of that drug. This article focuses on data concerning the predictability of dissolution

  19. Effects of the antituberculous drug ethambutol on zinc absorption, turnover and distribution in rats fed diet marginal and adequate in zinc

    Energy Technology Data Exchange (ETDEWEB)

    King, A.B.; Schwartz, R.

    1987-04-01

    Ethambutol, (CH/sub 3/CH/sub 2/-CH(CH/sub 2/OH)-NH-CH/sub 2/)/sub 2/ (EMB), is an oral antituberculous agent that is administered therapeutically over extended time periods. It has chelating properties and may affect mineral metabolism. Male weanling Sprague-Dawley rats received 0, 400 or 600 mg EMB per kilogram body weight daily by gavage for 30 d. They were fed a casein-based diet with either adequate (49 ppm) or marginal (11 ppm) zinc. Both adequate-Zn (AZn) and marginal-Zn (MZn) rats receiving EMB showed alopecia and dose-dependent reductions in feed intake, weight gain and feed efficiency. None of these changes was seen in rats fed the MZn diet without EMB. Serum and tissue zinc levels were similar in rats not receiving EMB, regardless of the dietary zinc level. Serum zinc was consistently lower in AZn and MZn rats receiving EMB than in rats without EMB. Apparent zinc absorption, measured by /sup 65/Zn balance, was higher in AZn rats receiving EMB than in AZn rats without EMB. Thus, changes in absorption could not account for lower serum zinc levels in EMB-treated rats. However, /sup 65/Zn turnover was also higher in EMB groups. This suggests that EMB may have increased urinary zinc losses resulting in reduced circulating zinc and a consequent increase in zinc absorption.

  20. Rapid on-site TLC-SERS detection of four antidiabetes drugs used as adulterants in botanical dietary supplements.

    Science.gov (United States)

    Zhu, Qingxia; Cao, Yongbing; Cao, Yingying; Chai, Yifeng; Lu, Feng

    2014-03-01

    A novel facile method has been established for rapid on-site detection of antidiabetes chemicals used to adulterate botanical dietary supplements (BDS) for diabetes. Analytes and components of pharmaceutical matrices were separated by thin-layer chromatography (TLC) then surface-enhanced Raman spectroscopy (SERS) was used for qualitative identification of trace substances on the HPTLC plate. Optimization and standardization of the experimental conditions, for example the method used for preparation of silver colloids, the mobile phase, and the concentration of colloidal silver, resulted in a very robust and highly sensitive method which enabled successful detection when the amount of adulteration was as low as 0.001 % (w/w). The method was also highly selective, enabling successful identification of some chemicals in extremely complex herbal matrices. The established TLC-SERS method was used for analysis of real BDS used to treat diabetes, and the results obtained were verified by liquid chromatography-triple quadrupole mass spectrometry (LC-MS-MS). The study showed that TLC-SERS could be used for effective separation and detection of four chemicals used to adulterate BDS, and would have good prospects for on-site qualitative screening of BDS for adulterants.

  1. The non-benzodiazepine anxiolytic drug etifoxine causes a rapid, receptor-independent stimulation of neurosteroid biosynthesis.

    Directory of Open Access Journals (Sweden)

    Jean Luc do Rego

    Full Text Available Neurosteroids can modulate the activity of the GABAA receptors, and thus affect anxiety-like behaviors. The non-benzodiazepine anxiolytic compound etifoxine has been shown to increase neurosteroid concentrations in brain tissue but the mode of action of etifoxine on neurosteroid formation has not yet been elucidated. In the present study, we have thus investigated the effect and the mechanism of action of etifoxine on neurosteroid biosynthesis using the frog hypothalamus as an experimental model. Exposure of frog hypothalamic explants to graded concentrations of etifoxine produced a dose-dependent increase in the biosynthesis of 17-hydroxypregnenolone, dehydroepiandrosterone, progesterone and tetrahydroprogesterone, associated with a decrease in the production of dihydroprogesterone. Time-course experiments revealed that a 15-min incubation of hypothalamic explants with etifoxine was sufficient to induce a robust increase in neurosteroid synthesis, suggesting that etifoxine activates steroidogenic enzymes at a post-translational level. Etifoxine-evoked neurosteroid biosynthesis was not affected by the central-type benzodiazepine (CBR receptor antagonist flumazenil, the translocator protein (TSPO antagonist PK11195 or the GABAA receptor antagonist bicuculline. In addition, the stimulatory effects of etifoxine and the triakontatetraneuropeptide TTN, a TSPO agonist, were additive, indicating that these two compounds act through distinct mechanisms. Etifoxine also induced a rapid stimulation of neurosteroid biosynthesis from frog hypothalamus homogenates, a preparation in which membrane receptor signalling is disrupted. In conclusion, the present study demonstrates that etifoxine stimulates neurosteroid production through a membrane receptor-independent mechanism.

  2. Fabrication of novel Si-doped hydroxyapatite/gelatine scaffolds by rapid prototyping for drug delivery and bone regeneration.

    Science.gov (United States)

    Martínez-Vázquez, F J; Cabañas, M V; Paris, J L; Lozano, D; Vallet-Regí, M

    2015-03-01

    Porous 3-D scaffolds consisting of gelatine and Si-doped hydroxyapatite were fabricated at room temperature by rapid prototyping. Microscopic characterization revealed a highly homogeneous structure, showing the pre-designed porosity (macroporosity) and a lesser in-rod porosity (microporosity). The mechanical properties of such scaffolds are close to those of trabecular bone of the same density. The biological behavior of these hybrid scaffolds is greater than that of pure ceramic scaffolds without gelatine, increasing pre-osteoblastic MC3T3-E1 cell differentiation (matrix mineralization and gene expression). Since the fabrication process of these structures was carried out at mild conditions, an antibiotic (vancomycin) was incorporated in the slurry before the extrusion of the structures. The release profile of this antibiotic was measured in phosphate-buffered saline solution by high-performance liquid chromatography and was adjusted to a first-order release kinetics. Vancomycin released from the material was also shown to inhibit bacterial growth in vitro. The implications of these results for bone tissue engineering applications are discussed. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  3. Rapid in situ repeatable analysis of drugs in powder form using reflectance near-infrared spectroscopy and multivariate calibration.

    Science.gov (United States)

    Melucci, Dora; Monti, Dario; D'Elia, Marcello; Luciano, Giorgio

    2012-01-01

    This study takes the first step toward in situ analysis of powder drugs which does not require any alteration of the samples. A fast, inexpensive analytical method based on reflectance near-infrared (NIR) spectrometry and multivariate calibration was applied. A diode-array fiber-optic portable spectrometer in the 900-1700 nm range was employed. Samples were laboratory-prepared ternary powders (diacetylmorphine, caffeine, and paracetamol). Partial least squares regression was applied. The choice of the standard samples for calibration and validation was performed through a D-optimal experimental design. The explained variance was higher than 90%, and the relative root mean square errors were <2%. The number of principal components (6) was very low when compared with the number of raw variables (356 absorbance values). Response plots showed slopes and intercepts were very close to optimal values. Correlation coefficients ranged between 0.909 and 0.989. The method here proposed proved to be competitive with Fourier transform NIR spectrometry. © 2011 American Academy of Forensic Sciences.

  4. The effect of E. coli STa enterotoxin on the absorption of weakly dissociable anti-malarial drugs from rat intestine in vivo.

    OpenAIRE

    Rawlings, J M; Lynch, J; Lucas, M. L.

    1991-01-01

    1. The effect of E. coli heat stable (STa) enterotoxin on the absorption of radiolabelled anti-malarial weak bases and their appearance in peripheral blood was assessed in vivo by a recirculation procedure in rat intestinal loops. 2. Enterotoxin increased the jejunal disappearance of quinine (P less than 0.05), trimethoprim (P less than 0.05), proguanil (P less than 0.05) and chloroquine (P less than 0.001) and left pyrimethamine disappearance unaltered. Peripheral blood levels of trimethopri...

  5. Rapid detection by direct analysis in real time-mass spectrometry (DART-MS) of psychoactive plant drugs of abuse: the case of Mitragyna speciosa aka "Kratom".

    Science.gov (United States)

    Lesiak, Ashton D; Cody, Robert B; Dane, A John; Musah, Rabi A

    2014-09-01

    Mitragyna speciosa, also known commonly as "Kratom" or "Ketum", is a plant with psychoactive properties that have been attributed to the presence of various indole alkaloids such as mitragynine and 7-hydroxymitragynine. M. speciosa use is gaining popularity internationally as a natural and legal alternative to narcotics. As a drug of abuse, its detection and identification are not straightforward, since M. speciosa plant material is not particularly distinctive. Here, we show that direct analysis in real time-mass spectrometry (DART-MS) can be used not only to rapidly identify M. speciosa plant material and distinguish it from other plants, but also to distinguish between M. speciosa plant varieties, based on differences between their chemical profiles. The method is rapid and the analysis expeditious. Plant material such as that found at a crime scene can be analyzed directly with no sample pre-preparation steps. Furthermore, we show that the basis set of principal components that permit characterization of the plant material can be used to positively identify M. speciosa. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  6. Rapid acquisition and modulation of colistin-resistance by an extensively drug-resistant Acinetobacter baumannii: case report and review of current literature

    Directory of Open Access Journals (Sweden)

    Jari Intra

    2016-10-01

    Full Text Available Acinetobacter baumannii has emerged as a major cause of healthcare-associated infections. It commonly expresses clinical resistance to multiple antimicrobial agents, and hence, it is considered the paradigm of an extensively drug-resistant (XDR bacterium. XDR A. baumannii is a rapidly emerging pathogen, especially in the intensive care unit (ICU, causing nosocomial infections including sepsis, ventilatorassociated pneumonia, meningitis, peritonitis, urinary tract infection, and central venous catheter-related infection. In the present report, we described an in vivo evolution of A. baumannii strain from a colistinsusceptibility to a colistin-resistance state. A 65-year-old male, who suffered a duodenal ulcer, two days after hospitalization and during the stay in ICU, contracted a pneumonia and peritoneal infection by a carbapenem-resistant A. baumannii strain. After a combination treatment with colistin, vancomycin plus imipenem, and within seven days, the pathogen rapidly evolved in seven days to a pandrug-resistant phenotype. As the antimicrobial treatment was stopped, the A. baumannii isolate changed another time its profile to colistin, becoming newly susceptible, showing a very high level of adaptability to external conditions. We also have reviewed here the current literature on this worryingly public health threat.

  7. Real-Time PCR and High-Resolution Melt Analysis for Rapid Detection of Mycobacterium leprae Drug Resistance Mutations and Strain Types

    Science.gov (United States)

    Li, Wei; Matsuoka, Masanori; Kai, Masanori; Thapa, Pratibha; Khadge, Saraswoti; Hagge, Deanna A.; Brennan, Patrick J.

    2012-01-01

    Drug resistance surveillance and strain typing of Mycobacterium leprae are necessary to investigate ongoing transmission of leprosy in regions of endemicity. To enable wider implementation of these molecular analyses, novel real-time PCR–high-resolution melt (RT-PCR-HRM) assays without allele-specific primers or probes and post-PCR sample handling were developed. For the detection of mutations within drug resistance-determining regions (DRDRs) of folP1, rpoB, and gyrA, targets for dapsone, rifampin, and fluoroquinolones, real-time PCR-HRM assays were developed. Wild-type and drug-resistant mouse footpad-derived strains that included three folP1, two rpoB, and one gyrA mutation types in a reference panel were tested. RT-PCR-HRM correctly distinguished the wild type from the mutant strains. In addition, RT-PCR-HRM analyses aided in recognizing samples with mixed or minor alleles and also a mislabeled sample. When tested in 121 sequence-characterized clinical strains, HRM identified all the folP1 mutants representing two mutation types, including one not within the reference panel. The false positives (PCR inhibition. A second set of RT-PCR-HRM assays for identification of three previously reported single nucleotide polymorphisms (SNPs) that have been used for strain typing were developed and validated in 22 reference and 25 clinical strains. Real-time PCR-HRM is a sensitive, simple, rapid, and high-throughput tool for routine screening known DRDR mutants in new and relapsed cases, SNP typing, and detection of minor mutant alleles in the wild-type background at lower costs than current methods and with the potential for quality control in leprosy investigations. PMID:22170923

  8. Food and drugs

    OpenAIRE

    Đaković-Švajcer Kornelija

    2002-01-01

    Food can exert a significant influence on the effects of certain drugs. The interactions between food and drugs can be pharmacokinetic and pharmacodynamic. Pharmacokinetic interactions most often take place on absorption and drug metabolism levels. Absorption can be either accelerated or delayed, increased or decreased, while drug metabolism can be either stimulated or inhibited. The factors which influence food-drug interactions are as follows: composition and physic-chemical properties of d...

  9. Medication absorption considerations in patients with postpyloric enteral feeding tubes.

    Science.gov (United States)

    McIntyre, Chelsey M; Monk, Heather M

    2014-04-01

    The gastrointestinal absorption sites of medications administered via postpyloric enteral feeding tubes were examined. Many issues must be considered when administering medications via the postpyloric route, including interactions with enteral feeds, additional toxicities, and the concern of whether the medication will be absorbed. Despite the potential clinical significance of this information, data regarding the gastrointestinal site of absorption for most medications are lacking. Gastrointestinal absorption sites for all drugs for which requests for information on absorption sites were received at our institution since 2008 (n = 124) were evaluated by reviewing the package insert, consulting tertiary references, conducting primary literature searches, or contacting the drug manufacturer. Seventy (56.5%) of the 124 drugs reviewed had information available regarding the site of absorption. Just 2 drugs required acid for absorption and thus should be administered only through the stomach, while 2 other drugs were found to bind extensively to tubing and should not be administered in this manner. For 3 drugs, increased absorption may occur when they are administered directly into the small bowel. Seven medications had decreased absorption when administered directly to the small bowel, and 10 drugs were clearly not absorbed when administered through either the duodenal or the jejunal route. The implications of absorption site should be considered for all patients receiving medications via postpyloric feeding tubes. Several medications cannot be administered through alternative routes because gastric acid is needed for their absorption, the medications may bind to the tubing, or drug absorption is altered at the intestinal site.

  10. Flue gas treatment with membrane gas absorption

    NARCIS (Netherlands)

    Klaassen, R.; Feron, P.H.M.; Jansen, A.E.

    1998-01-01

    Membrane gas absorption is a new, efficient and flexible way to carry out gas-liquid contacting operations with hollow fibre membranes. Advantages of gas absorption membranes over conventional G-L contactors are: -High specific surface area and rapid mass transfer resulting in very compact and low

  11. Calculation of absorption parameters for selected narcotic drugs in the energy range from 1 keV to 100 GeV

    Science.gov (United States)

    Akman, Ferdi; Kaçal, Mustafa Recep; Akdemir, Fatma; Araz, Aslı; Turhan, Mehmet Fatih; Durak, Rıdvan

    2017-04-01

    The total mass attenuation coefficients (μ/ρ), total molecular (σt,m), atomic (σt,a) and electronic (σt,e) cross sections, effective atomic numbers (Zeff) and electron density (NE) were computed in the wide energy region from 1 keV to 100 GeV for the selected narcotic drugs such as morphine, heroin, cocaine, ecstasy and cannabis. The changes of μ/ρ, σt,m, σt,a, σt,e, Zeff and NE with photon energy for total photon interaction shows the dominance of different interaction process in different energy regions. The variations of μ/ρ, σt,m, σt,a, σt,e, Zeff and NE depend on the atom number, photon energy and chemical composition of narcotic drugs. Also, these parameters change with number of elements, the range of atomic numbers in narcotic drugs and total molecular weight. These data can be useful in the field of forensic sciences and medical diagnostic.

  12. Validation of a rapid lateral flow test for the simultaneous determination of β-lactam drugs and flunixin in raw milk.

    Science.gov (United States)

    Douglas, David; Banaszewski, Katie; Juskelis, Rima; Al-Taher, Fadwa; Chen, Yang; Cappozzo, Jack; McRobbie, Lindsay; Salter, Robert S

    2012-07-01

    β-Lactam antibiotics are the most commonly used drugs on dairy farms. β-Lactam residues in milk are kept out of the human milk supply with good agricultural practices and mandatory truck screening performed by the dairy industry under Appendix N of the Pasteurized Milk Ordinance. Flunixin, a nonsteroidal and anti-inflammatory drug, appears in dairy cattle tissue residues with a frequency similar to the occurrence of penicillin G. This creates concern that flunixin residues could be in milk and would go undetected under current milk screening programs. A single test that combines mandatory β-lactam screening with voluntary flunixin screening is an economical approach for monitoring and controlling for potential flunixin or 5-hydroxyflunixin, the primary flunixin metabolite marker in milk. The objective of this study was to validate a β-lactam and flunixin rapid lateral flow test (LFT) and compare the results obtained with a liquid chromatography-triple quadrupole tandem mass spectrometry (LC-MS/MS) method for the simultaneous determination of flunixin and 5-hydroxyflunixin in raw milk with a limit of detection of , 1 ppb, equivalent to 1 ng/ml. Using the LFT, three combined manufactured lots of test strips detected penicillin G at 2.0 ppb, ampicillin at 6.8 ppb, amoxicillin at 5.9 ppb, cephapirin at 13.4 ppb, ceftiofur (total metabolites) at 63 ppb, and 5-hydroxyflunixin at 1.9 ppb at least 90% of the time with 95% confidence. The LFT also detected incurred flunixin milk samples that were analyzed with the LC-MS/MS and diluted to tolerance in raw milk. The detection levels for the LFT are lower than the U.S. safe levels or tolerances and qualify the test to be used in compliance with U.S. milk screening programs.

  13. Design and baseline findings of a large-scale rapid response to an HIV outbreak in people who inject drugs in Athens, Greece: the ARISTOTLE programme.

    Science.gov (United States)

    Hatzakis, Angelos; Sypsa, Vana; Paraskevis, Dimitrios; Nikolopoulos, Georgios; Tsiara, Chrissa; Micha, Katerina; Panopoulos, Anastasios; Malliori, Meni; Psichogiou, Mina; Pharris, Anastasia; Wiessing, Lucas; van de Laar, Marita; Donoghoe, Martin; Heckathorn, Douglas D; Friedman, Samuel R; Des Jarlais, Don C

    2015-09-01

    To (i) describe an intervention implemented in response to the HIV-1 outbreak among people who inject drugs (PWIDs) in Greece (ARISTOTLE programme), (ii) assess its success in identifying and testing this population and (iii) describe socio-demographic characteristics, risk behaviours and access to treatment/prevention, estimate HIV prevalence and identify risk factors, as assessed at the first participation of PWIDs. A 'seek, test, treat, retain' intervention employing five rounds of respondent-driven sampling. Athens, Greece (2012-13). A total of 3320 individuals who had injected drugs in the past 12 months. ARISTOTLE is an intervention that involves reaching out to high-risk, hard-to-reach PWIDs ('seek'), engaging them in HIV testing and providing information and materials to prevent HIV ('test') and initiating and maintaining anti-retroviral and opioid substitution treatment for those testing positive ('treat' and 'retain'). Blood samples were collected for HIV testing and personal interviews were conducted. ARISTOTLE recruited 3320 PWIDs during the course of 13.5 months. More than half (54%) participated in multiple rounds, resulting in 7113 visits. HIV prevalence was 15.1%. At their first contact with the programme, 12.5% were on opioid substitution treatment programmes and the median number of free syringes they had received in the preceding month was 0. In the multivariable analysis, apart from injection-related variables, homelessness was a risk factor for HIV infection in male PWIDs [odds ratio (OR) yes versus no = 1.89, 95% confidence interval (CI) = 1.41, 2.52] while, in female PWIDS, the number of sexual partners (OR for > 5 versus one partner in the past year = 4.12, 95% CI = 1.93, 8.77) and history of imprisonment (OR yes versus no = 2.76, 95% CI = 1.43, 5.31) were associated with HIV. In Athens, Greece, the ARISTOTLE intervention for identifying HIV-positive people among people who inject drugs (PWID) facilitated rapid

  14. Evaluation of the use of partition coefficients and molecular surface properties as predictors of drug absorption: a provisional biopharmaceutical classification of the list of national essential medi

    Directory of Open Access Journals (Sweden)

    NU Rahman

    2011-05-01

    Full Text Available Background and the purpose of the study: Partition coefficients (log D and log P and molecular surface area (PSA are potential predictors of the intestinal permeability of drugs. The aim of this investigation was to evaluate and compare these intestinal permeability indicators.   Methods: Aqueous solubility data were obtained from literature or calculated using ACD/Labs and ALOGPS. Permeability data were predicted based on log P, log D at pH 6.0 (log D6.0, and PSA.  Results: Metoprolol's log P, log D6.0 and a PSA of <65 Å correctly predicted 55.9%, 50.8% and 54.2% of permeability classes, respectively. Labetalol's log P, log D6.0, and PSA correctly predicted 54.2%, 64.4% and 61% of permeability classes, respectively. Log D6.0 correlated well (81% with Caco-2 permeability (Papp. Of the list of national essential medicines, 135 orally administered drugs were classified into biopharmaceutical classification system (BCS. Of these, 57 (42.2%, 28 (20.7%, 44 (32.6%, and 6 (4.4% were class I, II, III and IV respectively. Conclusion: Log D6.0 showed better prediction capability than log P. Metoprolol as permeability internal standard was more conservative than labetalol.

  15. Large volume sample stacking for rapid and sensitive determination of antidiabetic drug metformin in human urine and serum by capillary electrophoresis with contactless conductivity detection.

    Science.gov (United States)

    Tůma, Petr

    2014-06-06

    Two CE methods with contactless conductivity detection have been developed for determining the oral antidiabetic drug metformin in human urine and blood. The determination of metformin is performed on a separation capillary with an effective length of 14 cm, using a maximum voltage of 30 kV and with a small injection of 50-fold diluted urine into the capillary. Under these conditions, the migration time of metformin is 35s and the LOD is 0.3 μM. Large-volume sample stacking was used to determine low metformin levels in serum. The injection of a sample of serum deproteinized with acetonitrile was 10 times greater compared to the injected amount of urine. This enabled reduction of the LOD to 0.03 μM and the metformin migration time equalled 86 s. The undesirable solvent from sample zone was forced out of the capillary to ensure rapidity and good repeatability of the determination. The RSD values for the migration time are 0.1% for urine and 0.7% for serum; RSD for the peak areas equalled 1.4% for urine and 2.6% for serum. The developed CE technique was tested on performance of routine analyses of metformin in the urine and serum of patients suffering from type II diabetes mellitus. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Soil transmitted helminths and scabies in Zanzibar, Tanzania following mass drug administration for lymphatic filariasis - a rapid assessment methodology to assess impact

    Directory of Open Access Journals (Sweden)

    Mohammed Khalfan A

    2012-12-01

    Full Text Available Abstract Background Ivermectin and albendazole are used in annual mass drug administration (MDA for the lymphatic filariasis elimination programmes in African countries co-endemic for onchocerciasis, but have additional impact on soil transmitted helminths and the ectoparasitic mite which causes scabies. Assessing these collateral impacts at scale is difficult due to the insensitivity of available parasite detection techniques. Methods The numbers of cases diagnosed with intestinal helminths and scabies and who received prescriptions for treatment were evaluated in 50 health centres in Zanzibar. Records were examined from 2000, prior to the initiation of MDA to 2005, after six rounds of MDA for lymphatic filariasis had taken place. Results Health centre records showed a consistent decline in the number of cases of intestinal helminths and scabies diagnosed by community health workers in Zanzibar and the number of prescriptions issued across five age groups. A 90-98% decline in soil transmitted helminths and 68-98% decline in scabies infections were recorded. Poisson regression models aggregated to both the island-level and district-level indicated that the decline was statistically significant. Conclusions The described method of examining health centre records has the potential for use on a large scale, despite limitations, as a rapid method to evaluate the impacts resulting from both lymphatic filariasis and onchocerciasis MDA. This would result in a reduction in the need for parasitological evaluations to determine prevalence and intensity.

  17. Biopharmaceutic classification of drugs revisited.

    Science.gov (United States)

    Daousani, Chrysa; Macheras, Panos

    2016-12-01

    The biopharmaceutics classification system (BCS) was based on the tube model of the intestinal lumen. This model considers constant drug permeability along the intestines, a plug flow fluid with the suspended drug particles moving with the fluid, and dissolution in the small particle limit. Since then the research work focusing on drug gastrointestinal (GI) absorption phenomena and processes rely on the classical laws of transport, diffusion and kinetics; however, the homogeneous assumptions associated with the well-stirred Euclidean media, where the classical laws of diffusion and kinetics apply, have been questioned in the past. In this work we explore the biopharmaceutic classification of drugs using a heterogeneous pseudo steady-state model of oral drug absorption. The fraction of dose absorbed (Fabs) was expressed as a function of two time-dependent processes where time dependent coefficients govern drug absorption and non-absorption processes. Fundamental drug properties like the absorption potential are correlated with Fabs and allow the biopharmaceutic classification of drugs taking into account the heterogeneous aspects of oral drug absorption. This analysis reveals that for Class I drugs no time dependency is expected for both absorption and non absorption processes since the gastric emptying is controlling the absorption of Class I drugs while the completion of absorption (Fabs>90%) is terminated along the first part of the jejunum. Due to the biopharmaceutical properties of Class II, III and IV drugs, these drugs travel throughout the GI tract and therefore both absorption and non absorption processes will exhibit time dependency. Thus, the calculation of Fabs (<90%) for Class II, III and IV is dependent on the estimates of the time exponents of time dependent coefficients controlling drug absorption e.g. dissolution, uptake or non absorption e.g. precipitation. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Effect of food intake and co-administration of placebo self-nanoemulsifying drug delivery systems on the absorption of cinnarizine in healthy human volunteers

    DEFF Research Database (Denmark)

    Christiansen, Martin Lau; Holm, Rene; Abrahamsson, Bertil

    2016-01-01

    the stability issue. The two aims for this present study were therefore; i) to investigate if a nutritional drink, Fresubin Energy®, could induce food effect in humans for the poorly soluble compound cinnarizine; and ii) to investigate if co-administration of a self-nano-emulsifying drug delivery systems...... between dosing. The fed state was induced using a nutritional drink (Fresubin Energy®) and gastric emptying was assessed by administration of paracetamol as a marker. The pharmacokinetic analysis showed that the nutritional drink delayed the uptake and increased the fraction of absorbed cinnarizine......, indicative of a food effect on the compound. This was in agreement with a previous dog study and indicates that the nutritional drink can be used for inducing the same level of food effect in humans. Though not statistically significant, the co-administration of SNEDDS exhibited a tendency towards...

  19. Examination of oral absorption and lymphatic transport of halofantrine in a triple-cannulated canine model after administration in self-microemulsifying drug delivery systems (SMEDDS) containing structured triglycerides

    DEFF Research Database (Denmark)

    Holm, René; Porter, Christopher J H; Edwards, Glenn A

    2003-01-01

    The potential for lipidic self-microemulsifying drug delivery systems (SMEDDS) containing triglycerides with a defined structure, where the different fatty acids on the glycerol backbone exhibit different metabolic fate, to improve the lymphatic transport and the portal absorption of a poorly water......-soluble drug, halofantrine, were investigated in fasted lymph cannulated canines. Two different structured triglycerides were incorporated into the SMEDDS; 1,3-dioctanoyl-2-linoleyl-sn-glycerol (C8:0-C18:2-C8:0) (MLM) and 1,3-dilinoyl-2-octanoyl-sn-glycerol (C18:2-C8:0-C18:2) (LML). A previously optimised...... SMEDDS formulation for halofantrine, comprising of triglyceride, Cremophor EL, Maisine 35-1 and ethanol was selected for bioavailability assessment. The extent of lymphatic transport via the thoracic duct was 17.9% of the dose for the animals dosed with the MLM SMEDDS and 27.4% for LML. Also the plasma...

  20. Simultaneous multi-residue determination of twenty one veterinary drugs in poultry litter by modeling three-way liquid chromatography with fluorescence and absorption detection data.

    Science.gov (United States)

    Teglia, Carla M; Peltzer, Paola M; Seib, Silvia N; Lajmanovich, Rafael C; Culzoni, María J; Goicoechea, Héctor C

    2017-05-15

    A method for the simultaneous investigation of twenty one veterinary active ingredients in poultry litter based on MCR-ALS modeling of three-way liquid chromatography with fluorescence and UV detection data is presented. The chromatographic procedure was optimized in terms of both the nature of the organic solvent and the pH of the mobile phase to maximize the resolution of the analytes. In order to improve the simultaneous extraction efficiency of the twenty one veterinary drugs, a simplex-centroid design with combinations of the three components of the extracting mixture, i.e. MeOH, ACN and sodium phosphate buffer 10mmolL(-1) pH =3.50, was carried out. The second-order advantage was exploited in the analysis of highly complex samples containing unmodeled components. The qualitative and quantitative results showed that the application of MCR-ALS was appropriate to resolve highly overlapped peaks in the presence of unknown matrix compounds. Limits of quantification, relative errors of prediction (REP) and average recoveries ranging from 0.02 to 0.61µgg(-1), 3.09-9.35% and 91.0-105.6%, respectively, were obtained. Eventually, the method was successfully applied to the determination of active ingredients in five poultry litter samples collected from different poultry livestock in Argentina. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Surface modification of liposomes using polymer-wheat germ agglutinin conjugates to improve the absorption of peptide drugs by pulmonary administration.

    Science.gov (United States)

    Murata, Mitsutaka; Yonamine, Takashi; Tanaka, Shota; Tahara, Kohei; Tozuka, Yuichi; Takeuchi, Hirofumi

    2013-04-01

    In this study, we investigated the feasibility of a system based on liposomal surface modification with a novel mucoadhesive polymer-lectin conjugate for the pulmonary delivery of therapeutic peptides and proteins. We covalently attached wheat germ agglutinin (WGA), a ligand that specifically interacts with alveolar epithelial cells, to carbopol (CP), a mucoadhesive polymer, using the carbodiimide method and then evaluated the efficacy and potential toxicity of CP-WGA surface-modified liposomes in vivo and in vitro. In association studies, CP-WGA modification enhanced the interaction with A549 lung epithelial cells compared with unmodified or CP-modified liposomes. This increased association was dependent on temperature and the surface concentration of free WGA. These results suggested synergy of WGA and CP, and retention of the biological cell binding activity of WGA, leading to improved liposome-cell interactions. Moreover, improvement of liposomal bioadhesion to lung epithelia significantly enhanced and prolonged the therapeutic efficacy of calcitonin, a model peptide drug, without any evidence of toxicity, following administration of calcitonin-loaded CP-WGA-modified liposomes. Hence, surface modification of liposomes with CP-WGA has potential for effective pulmonary administration of peptides. Copyright © 2013 Wiley Periodicals, Inc.

  2. Low Buffer Capacity and Alternating Motility along the Human Gastrointestinal Tract: Implications for in Vivo Dissolution and Absorption of Ionizable Drugs.

    Science.gov (United States)

    Hens, Bart; Tsume, Yasuhiro; Bermejo, Marival; Paixao, Paulo; Koenigsknecht, Mark J; Baker, Jason R; Hasler, William L; Lionberger, Robert; Fan, Jianghong; Dickens, Joseph; Shedden, Kerby; Wen, Bo; Wysocki, Jeffrey; Loebenberg, Raimar; Lee, Allen; Frances, Ann; Amidon, Greg; Yu, Alex; Benninghoff, Gail; Salehi, Niloufar; Talattof, Arjang; Sun, Duxin; Amidon, Gordon L

    2017-12-04

    In this study, we determined the pH and buffer capacity of human gastrointestinal (GI) fluids (aspirated from the stomach, duodenum, proximal jejunum, and mid/distal jejunum) as a function of time, from 37 healthy subjects after oral administration of an 800 mg immediate-release tablet of ibuprofen (reference listed drug; RLD) under typical prescribed bioequivalence (BE) study protocol conditions in both fasted and fed states (simulated by ingestion of a liquid meal). Simultaneously, motility was continuously monitored using water-perfused manometry. The time to appearance of phase III contractions (i.e., housekeeper wave) was monitored following administration of the ibuprofen tablet. Our results clearly demonstrated the dynamic change in pH as a function of time and, most significantly, the extremely low buffer capacity along the GI tract. The buffer capacity on average was 2.26 μmol/mL/ΔpH in fasted state (range: 0.26 and 6.32 μmol/mL/ΔpH) and 2.66 μmol/mL/ΔpH in fed state (range: 0.78 and 5.98 μmol/mL/ΔpH) throughout the entire upper GI tract (stomach, duodenum, and proximal and mid/distal jejunum). The implication of this very low buffer capacity of the human GI tract is profound for the oral delivery of both acidic and basic active pharmaceutical ingredients (APIs). An in vivo predictive dissolution method would require not only a bicarbonate buffer but also, more significantly, a low buffer capacity of dissolution media to reflect in vivo dissolution conditions.

  3. Rapid discrimination and determination of antibiotics drugs in plastic syringes using near infrared spectroscopy with chemometric analysis: Application to amoxicillin and penicillin.

    Science.gov (United States)

    Lê, Laetitia Minh Mai; Eveleigh, Luc; Hasnaoui, Ikram; Prognon, Patrice; Baillet-Guffroy, Arlette; Caudron, Eric

    2017-05-10

    The aim of this study was to investigate near infrared spectroscopy (NIRS) combined to chemometric analysis to discriminate and quantify three antibiotics by direct measurement in plastic syringes.Solutions of benzylpenicillin (PENI), amoxicillin (AMOX) and amoxicillin/clavulanic acid (AMOX/CLAV) were analyzed at therapeutic concentrations in glass vials and plastic syringes with NIR spectrometer by direct measurement. Chemometric analysis using partial least squares regression and discriminative analysis was conducted to develop qualitative and quantitative calibration models. Discrimination of the three antibiotics was optimal for concentrated solutions with 100% of accuracy. For quantitative analysis, the three antibiotics furnished a linear response (R²>0.9994) for concentrations ranging from 0.05 to 0.2 g/mL for AMOX, 0.1 to 1.0 MUI/mL for PENI and 0.005 to 0.05 g/mL for AMOX/CLAV with excellent repeatability (maximum 1.3%) and intermediate precision (maximum of 3.2%). Based on proposed models, 94.4% of analyzed AMOX syringes, 80.0% of AMOX/CLAV syringes and 85.7% of PENI syringes were compliant with a relative error including the limit of ± 15%.NIRS as rapid, non-invasive and non-destructive analytical method represents a potentially powerful tool to further develop for securing the drug administration circuit of healthcare institutions to ensure that patients receive the correct product at the right dose. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Identification of Staphylococcus aureus α-hemolysin as a protein drug that is secreted by anticancer bacteria and rapidly kills cancer cells.

    Science.gov (United States)

    Swofford, Charles A; St Jean, Adam T; Panteli, Jan T; Brentzel, Zachary J; Forbes, Neil S

    2014-06-01

    Targeted bacterial delivery of anticancer proteins has the ability to overcome therapeutic resistance in tumors that limits the efficacy of chemotherapeutics. The ability of bacteria to specifically target tumors allows for delivery of aggressive proteins that directly kill cancer cells and cannot be administered systemically. However, few proteins have been tested for this purpose. To identify effective molecules, we systematically sorted proteins that have been shown to cause mammalian cell death. The genes for five proteins were selected and cloned into Escherichia coli and Salmonella. Supernatant from cultures of the transformed bacteria was applied to flasks of MCF-7 mammary carcinoma cells to identify proteins that (1) were expressed, (2) secreted, and (3) rapidly killed cancer cells. Time-lapse images were taken to visualize mammalian cell morphology. Of the investigated proteins, α-hemolysin from Staphylococcus aureus (SAH) was the most promising because it was secreted, caused trauma to cellular membranes, and induced oncosis in 18 min. After exposure for 6 h, SAH decreased cell viability by 90%. In comparison, the positive control, Pseudomonas aeruginosa exotoxin A (PEA), required 11 days to achieve a similar effect, when administered at 3,000 times its LC50 . The maximum death rate induced by SAH was calculated to be a reduction in cell viability of 7.1% per min, which was 200-fold faster than the PEA control. Two proteins, Dermonecrotic Toxin and Phospholipase C were active when extracted from the bacterial cytoplasm but were not secreted. This investigation revealed for the first time SAH as a potent anticancer drug for delivery by bacteria because of its ability to be secreted in a fully functional form and aggressively kill cancer cells. © 2014 Wiley Periodicals, Inc.

  5. Comminution of ibuprofen to produce nano-particles for rapid dissolution.

    Science.gov (United States)

    Plakkot, S; de Matas, M; York, P; Saunders, M; Sulaiman, B

    2011-08-30

    A critical problem associated with poorly soluble drugs is low and variable bioavailability derived from slow dissolution and erratic absorption. The preparation of nano-formulations has been identified as an approach to enhance the rate and extent of drug absorption for compounds demonstrating limited aqueous solubility. A new technology for the production of nano-particles using high speed, high efficiency processes that can rapidly generate nano-particles with rapid dissolution rate has been developed. Size reduction of a low melting ductile model compound was achieved in periods less than 1h. Particle size reduction of ibuprofen using this methodology resulted in production of crystalline particles with average diameter of approximately 270nm. Physical stability studies showed that the nano-suspension remained homogeneous with slight increases in mean particle size, when stored at room temperature and under refrigerated storage conditions 2-8°C for up to 2 days. Powder containing crystalline drug was prepared by spray-drying ibuprofen nano-suspensions with mannitol dissolved in the aqueous phase. Dissolution studies showed similar release rates for the nano-suspension and powder which were markedly improved compared to a commercially available drug product. Ibuprofen nano-particles could be produced rapidly with smaller sizes achieved at higher suspension concentrations. Particles produced in water with stabilisers demonstrated greatest physical stability, whilst rapid dissolution was observed for the nano-particles isolated in powder form. Copyright © 2011 Elsevier B.V. All rights reserved.

  6. A field evaluation of the Hardy TB MODS Kit™ for the rapid phenotypic diagnosis of tuberculosis and multi-drug resistant tuberculosis.

    Directory of Open Access Journals (Sweden)

    Laura Martin

    Full Text Available Even though the WHO-endorsed, non-commercial MODS assay offers rapid, reliable TB liquid culture and phenotypic drug susceptibility testing (DST at lower cost than any other diagnostic, uptake has been patchy. In part this reflects misperceptions about in-house assay quality assurance, but user convenience of one-stop procurement is also important. A commercial MODS kit was developed by Hardy Diagnostics (Santa Maria, CA, USA with PATH (Seattle, WA, USA to facilitate procurement, simplify procedures through readymade media, and enhance safety with a sealing silicone plate lid. Here we report the results from a large-scale field evaluation of the MODS kit in a government service laboratory.2446 sputum samples were cultured in parallel in Lowenstein-Jensen (LJ, conventional MODS and in the MODS kit. MODS kit DST was compared with conventional MODS (direct DST and proportion method (indirect DST. 778 samples (31.8% were Mycobacterium tuberculosis culture-positive. Compared to conventional MODS the sensitivity, specificity, positive, and negative predictive values (95% confidence intervals of the MODS Kit were 99.3% (98.3-99.8%, 98.3% (97.5-98.8%, 95.8% (94.0-97.1%, and 99.7% (99.3-99.9%. Median (interquartile ranges time to culture-positivity (and rifampicin and isoniazid DST was 10 (9-13 days for conventional MODS and 8.5 (7-11 for MODS Kit (p<0.01. Direct rifampicin and isoniazid DST in MODS kit was almost universally concordant with conventional MODS (97.9% agreement, 665/679 evaluable samples and reference indirect DST (97.9% agreement, 687/702 evaluable samples.MODS kit delivers performance indistinguishable from conventional MODS and offers a convenient, affordable alternative with enhanced safety from the sealing silicone lid. The availability in the marketplace of this platform, which conforms to European standards (CE-marked, readily repurposed for second-line DST in the near future, provides a fresh opportunity for improving equity of

  7. D-xylose absorption

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003606.htm D-xylose absorption To use the sharing features on this page, please enable JavaScript. D-xylose absorption is a laboratory test to determine ...

  8. Country-wide surveillance of molecular markers of antimalarial drug resistance in Senegal by use of positive Malaria Rapid Diagnostic Tests

    DEFF Research Database (Denmark)

    Ndiaye, Magatte; Sow, Doudou; Nag, Sidsel

    2017-01-01

    In Senegal, antimalarial drugs used in treatment and prevention of malaria are one of the main reasons for the current success in controlling malaria. However, the successful control of malaria is highly dependent on continued effectiveness of these drugs which may be compromised by the spread of...

  9. Development of a high-throughput in vitro intestinal lipolysis model for rapid screening of lipid-based drug delivery systems

    DEFF Research Database (Denmark)

    Mosgaard, Mette D; Sassene, Philip; Mu, Huiling

    2015-01-01

    (DIVL) model with regard to the extent of lipid digestion and drug distribution of two poorly soluble model drugs (cinnarizine and danazol), during digestion of three LbDDS (LbDDS I-III). RESULT: The HTP model was able to maintain pH around 6.5 during digestion, without the addition of NaOH...

  10. Psychological absorption. Affect investment in marijuana intoxication.

    Science.gov (United States)

    Fabian, W D; Fishkin, S M

    1991-01-01

    Absorption (a trait capacity for total attentional involvement) was reported to increase during episodes of marijuana intoxication. Several subsets of the absorption scale items specifically characterized marijuana intoxication, and groups of users and nonusers showed differential affective involvement with these experiences. Additionally, within the drug-using group, a positive correlation between frequency of marijuana use and affective ratings of these experiences was found. The findings support the hypothesis that a specific type of alteration in consciousness that enhances capacity for total attentional involvement (absorption) characterizes marijuana intoxication, and that this enhancement may act as a reinforcer, possibly influencing future use.

  11. Enhancing TB case detection: experience in offering upfront Xpert MTB/RIF testing to pediatric presumptive TB and DR TB cases for early rapid diagnosis of drug sensitive and drug resistant TB.

    Science.gov (United States)

    Raizada, Neeraj; Sachdeva, Kuldeep Singh; Nair, Sreenivas Achuthan; Kulsange, Shubhangi; Gupta, Radhey Shayam; Thakur, Rahul; Parmar, Malik; Gray, Christen; Ramachandran, Ranjani; Vadera, Bhavin; Ekka, Shobha; Dhawan, Shikha; Babre, Ameet; Ghedia, Mayank; Alavadi, Umesh; Dewan, Puneet; Khetrapal, Mini; Khanna, Ashwini; Boehme, Catharina; Paramsivan, Chinnambedu Nainarappan

    2014-01-01

    Diagnosis of pulmonary tuberculosis (PTB) in children is challenging due to difficulties in obtaining good quality sputum specimens as well as the paucibacillary nature of disease. Globally a large proportion of pediatric tuberculosis (TB) cases are diagnosed based only on clinical findings. Xpert MTB/RIF, a highly sensitive and specific rapid tool, offers a promising solution in addressing these challenges. This study presents the results from pediatric groups taking part in a large demonstration study wherein Xpert MTB/RIF testing replaced smear microscopy for all presumptive PTB cases in public health facilities across India. The study covered a population of 8.8 million across 18 programmatic sub-district level tuberculosis units (TU), with one Xpert MTB/RIF platform established at each study TU. Pediatric presumptive PTB cases (both TB and Drug Resistant TB (DR-TB)) accessing any public health facilities in study area were prospectively enrolled and tested on Xpert MTB/RIF following a standardized diagnostic algorithm. 4,600 pediatric presumptive pulmonary TB cases were enrolled. 590 (12.8%, CI 11.8-13.8) pediatric PTB were diagnosed. Overall 10.4% (CI 9.5-11.2) of presumptive PTB cases had positive results by Xpert MTB/RIF, compared with 4.8% (CI 4.2-5.4) who had smear-positive results. Upfront Xpert MTB/RIF testing of presumptive PTB and presumptive DR-TB cases resulted in diagnosis of 79 and 12 rifampicin resistance cases, respectively. Positive predictive value (PPV) for rifampicin resistance detection was high (98%, CI 90.1-99.9), with no statistically significant variation with respect to past history of treatment. Upfront access to Xpert MTB/RIF testing in pediatric presumptive PTB cases was associated with a two-fold increase in bacteriologically-confirmed PTB, and increased detection of rifampicin-resistant TB cases under routine operational conditions across India. These results suggest that routine Xpert MTB/RIF testing is a promising solution to

  12. [Study on lead absorption in pumpkin by atomic absorption spectrophotometry].

    Science.gov (United States)

    Li, Zhen-Xia; Sun, Yong-Dong; Chen, Bi-Hua; Li, Xin-Zheng

    2008-07-01

    A study was carried out on the characteristic of lead absorption in pumpkin via atomic absorption spectrophotometer. The results showed that lead absorption amount in pumpkin increased with time, but the absorption rate decreased with time; And the lead absorption amount reached the peak in pH 7. Lead and cadmium have similar characteristic of absorption in pumpkin.

  13. Rapid manufacturing for microfluidics

    CSIR Research Space (South Africa)

    Land, K

    2012-10-01

    Full Text Available . Microfluidics is at the forefront of developing solutions for drug discovery, diagnostics (from glucose tests to malaria and TB testing) and environmental diagnostics (E-coli monitoring of drinking water). In order to quickly implement new designs, a rapid...

  14. Topical absorption and systemic toxicity.

    Science.gov (United States)

    Alikhan, Fatima Sasha; Maibach, Howard

    2011-09-01

    Dermal absorption of some chemicals and drugs can cause systemic toxicity. We evaluated several case reports from the past decade, which discuss the dermal absorption of a specific chemical and potential local and systemic effects. We focused on herbicide and pesticide exposure along with exposure to cutaneous medication, occupational contact, and cosmeceutical exposure. Although causality cannot be established in most cases, it is critical to be aware of the possible effects of topical absorption that may not be immediately apparent. We recommended further studies on specific chemicals to ascertain causality and determine the highest exposure level with no observed adverse affect level (NOAEL) and the reference dose (RfD). Post-marketing epidemiology data in most geographical areas are markedly limited. A weak link in public health resides in the inadequate reporting and workup of alleged chemically related adverse effects. This arena mandates a re-thinking of how to increase this reporting, and workup, as a backup to our preclinical and clinical studies. Public awareness and funding will be rewarded by increased evidence to backup pre-approval pre-marketing studies.

  15. QSPR Studies on Aqueous Solubilities of Drug-Like Compounds

    Directory of Open Access Journals (Sweden)

    Eduardo A. Castro

    2009-06-01

    Full Text Available A rapidly growing area of modern pharmaceutical research is the prediction of aqueous solubility of drug-sized compounds from their molecular structures. There exist many different reasons for considering this physico-chemical property as a key parameter: the design of novel entities with adequate aqueous solubility brings many advantages to preclinical and clinical research and development, allowing improvement of the Absorption, Distribution, Metabolization, and Elimination/Toxicity profile and “screenability” of drug candidates in High Throughput Screening techniques. This work compiles recent QSPR linear models established by our research group devoted to the quantification of aqueous solubilities and their comparison to previous research on the topic.

  16. Use of Optical Imaging Technology in the Validation of a New, Rapid, Cost-Effective Drug Screen as Part of a Tiered In Vivo Screening Paradigm for Development of Drugs To Treat Cutaneous Leishmaniasis.

    Science.gov (United States)

    Caridha, Diana; Parriot, Sandi; Hudson, Thomas H; Lang, Thierry; Ngundam, Franklyn; Leed, Susan; Sena, Jenell; Harris, Michael; O'Neil, Michael; Sciotti, Richard; Read, Lisa; Lecoeur, Herve; Hickman, Mark; Grogl, Max

    2017-04-01

    In any drug discovery and development effort, a reduction in the time of the lead optimization cycle is critical to decrease the time to license and reduce costs. In addition, ethical guidelines call for the more ethical use of animals to minimize the number of animals used and decrease their suffering. Therefore, any effort to develop drugs to treat cutaneous leishmaniasis requires multiple tiers of in vivo testing that start with higher-throughput efficacy assessments and progress to lower-throughput models with the most clinical relevance. Here, we describe the validation of a high-throughput, first-tier, noninvasive model of lesion suppression that uses an in vivo optical imaging technology for the initial screening of compounds. A strong correlation between luciferase activity and the parasite load at up to 18 days postinfection was found. This correlation allows the direct assessment of the effects of drug treatment on parasite burden. We demonstrate that there is a strong correlation between drug efficacy measured on day 18 postinfection and the suppression of lesion size by day 60 postinfection, which allows us to reach an accurate conclusion on drug efficacy in only 18 days. Compounds demonstrating a significant reduction in the bioluminescence signal compared to that in control animals can be tested in lower-throughput, more definitive tests of lesion cure in BALB/c mice and Golden Syrian hamsters (GSH) using Old World and New World parasites. Copyright © 2017 Caridha et al.

  17. Membrane Gas Absorption

    NARCIS (Netherlands)

    Jansen, A.E.; Klaassen, R.; Feron, P.H.M.

    1995-01-01

    Membrane gas absorption processes are absorption processes utilising hollow fibre membranes as contacting media for gas and liquid flows. The principle of operation and engineering aspects are discussed, followed by discussion of a number of typical applications. Benefits in terms of operation,

  18. Nutrition and magnesium absorption

    NARCIS (Netherlands)

    Brink, E.J.

    1992-01-01

    The influence of various nutrients present in dairy products and soybean-based products on absorption of magnesium has been investigated. The studies demonstrate that soybean protein versus casein lowers apparent magnesium absorption in rats through its phytate component. However, true

  19. Solar absorption surface panel

    Science.gov (United States)

    Santala, Teuvo J.

    1978-01-01

    A composite metal of aluminum and nickel is used to form an economical solar absorption surface for a collector plate wherein an intermetallic compound of the aluminum and nickel provides a surface morphology with high absorptance and relatively low infrared emittance along with good durability.

  20. Absorption mechanism of three curcumin constituents through in situ intestinal perfusion method

    Directory of Open Access Journals (Sweden)

    Y.-H. Wang

    2017-09-01

    Full Text Available This study aimed to investigate the absorption mechanism of three curcumin constituents in rat small intestines. Self-emulsification was used to solubilize the three curcumin constituents, and the rat in situ intestinal perfusion method was used to study factors on drug absorption, including drug mass concentration, absorption site, and the different types and concentrations of absorption inhibitors. Within the scope of experimental concentrations, three curcumin constituents were absorbed in rat small intestines through the active transport mechanism.

  1. Drug Transporters in the Intestine

    DEFF Research Database (Denmark)

    Steffansen, Bente

    2016-01-01

    and exemplify their roles in drug absorption/exsorption and in drug-drug interactions (DDIs). Although focus in the present Chapter is on DTs that are mentioned in American and European regulatory guidances, the intestinal transporters for nutrients and endogens (endogenous compounds) are also briefly...... that may impact drug absorption. Thus absorptive transporters may facilitate BA of APIs that are substrates/victims for the transporters and have permeability-limited absorption, i.e. those that are classified in the biopharmaceutics classification system (BCS) Class 3 and 4. On the other hand, exsorptive...... transporters may restrict BA of APIs that are victims for these efflux transporters, especially those APIs classified to have solubility-limited absorption, i.e. compounds in BCS Class 2 and 4. The aim of the present Chapter is to review drug transporters (DTs) present within the intestine and to discuss...

  2. Development of a lateral-flow assay for rapid screening of the performance-enhancing sympathomimetic drug clenbuterol used in animal production; food safety assessments.

    Science.gov (United States)

    Lai, Weihua; Xu, Yang; Fung, Daniel Y C; Xiong, Yonghua

    2007-01-01

    A lateral-flow assay that could provide visual evidence of the presence of clenbuterol in swine urine was developed. Colloidal gold was prepared and conjugated with anti-clenbuterol monoclonal antibody. Immunochromatographic test strips were produced, and then, 210 samples were tested on these strips. Analysis was completed in 10 min. Detection limit was 3 ppb of clenbuterol. Parallel GC-MS data indicated that clenbuterol rapid detection strip had no false negative. The false positive rate was 4.4%. Immunochromatographic strip has great applied value in the food safety field because it possesses benefits of sensitivity, stability, reproducibility, ease of use and inexpensive.

  3. [Advances in studies on absorption, distribution, metabolism of flavonoids].

    Science.gov (United States)

    Lv, Peng; Huang, Xiao-Wu; Lv, Qiu-Jun

    2007-10-01

    Plenty of data and tests suggested that flavonoids have strong physiological and pharmacological activities. In this paper, the absorption, distribution and metabolism of flavonoids in gaster, gut and liver were introduced. The research of absorption, distribution and metabolism on flavonoids will provide theoretical basis for developing new drugs of flavoniods.

  4. Rapid detection of extensively drug-resistant (XDR-TB) strains from multidrug-resistant tuberculosis (MDR-TB) cases isolated from smear-negative pulmonary samples in an Intermediate Reference Laboratory in India.

    Science.gov (United States)

    Vashistha, Himanshu; Hanif, M; Saini, Sanjeev; Khanna, Ashwani; Sharma, Srashty; Sidiq, Zeeshan; Ahmed, Vasim; Dubey, Manoj; Chopra, K K; Shrivastava, Divya

    2016-07-01

    Direct sputum smear microscopy is commonly used for diagnosing tuberculosis (TB). The objectives of the study were first, to determine the recovery of Mycobacterium tuberculosis in smear-negative sputum samples through liquid culture (using MGIT 960) and solid culture (using LJ slant) and second, to screen multidrug-resistant isolates through line probe assay and further third, to identify XDR isolates through MGIT second-line DST from these positive MDR cultures in Delhi region. In this study, the sample size was 717 (sputum smear AFB negative and culture positive for M. tuberculosis complex by both solid and liquid culture methods) MDRTB suspects who were enrolled from January 2014 to December 2014 at the Intermediate Reference Laboratory in New Delhi Tuberculosis Centre, New Delhi. Rapid line probe assay was performed on all culture-positive samples, which were direct smear-negative specimens, and LPA-confirmed MDR samples were tested on MGIT 960 second-line DST for identification of XDR strains. An overall increase in the culture positivity (9.4%) among these smear-negative cases shows a good sign of recovery from M. tuberculosis infection in these samples. 717 (9.4%) positive cultures (MGIT+LJ) were subjected to line probe assay. Out of these 717 cultures, 9 (1.2%) were confirmed as NTM, 50 (7%) were MDR, 4 (0.6%) were mono-rifampicin resistant and 654 (91.2%) cultures were sensitive to both drugs Rif and Inh, respectively. Out of these 54 (50 MDR +4 mono-RIF resistant) cultures as screened by LPA, 1 (1.8%) was XDR, 10 (18.6%) were mono-ofloxacin resistant and 1 (1.8%) was mono-Kanamycin resistant. Sensitivity to both drugs KAN and OFX was seen in 42 (77.8%) cultures. Since the bacterial load in direct smear-negative suspected MDR samples is less, it is important to recover mycobacteria by rapid liquid culture method in such samples. Initial screening for MDRTB is to be done in such cases by performing rapid molecular genotypic drug susceptibility test such as

  5. Class I antiarrhythmics inhibit Na+ absorption and Cl- secretion in rabbit descending colon epithelium.

    Science.gov (United States)

    Plass, Herbert; Charisius, Markus; Wyskovsky, Wolfgang; Amor, Florian; Turnheim, Klaus; Wiener, Hubert

    2005-06-01

    To clarify the mechanism of the diarrhea associated with the clinical use of antiarrhythmic drugs we assessed the effects of these agents on transepithelial Na+ absorption and Cl- secretion, on basolateral K+ conductance, and on the properties of single basolateral K+ channels of rabbit colon epithelium. Quinidine and propafenone, both at 10 microM, inhibited Na+ absorption by 27 and 38% respectively, compared with 50% with 5 mM Ba2+. The other tested class I antiarrhythmics disopyramide, mexiletine, lidocaine, and flecainide decreased Na+ current by 9-13%. Procainamide and the class III antiarrhythmics N-acetylprocainamide, sotalol, ibutilide, and amiodarone were no or were very weak inhibitors of Na+ absorption. Cl- secretion, stimulated with the adenosine analogue NECA (5'-N-ethylcarboxamide-adenosine), was reduced by 54% with quinidine and by 29% with propafenone compared with 100% with Ba2+. Mexiletine, lidocaine, and flecainide inhibited Cl- secretion by 10-23%, whereas the class III antiarrhythmics were no or were weak inhibitors. Those antiarrhythmics that inhibited Na+ and Cl- transport also reduced basolateral K+ conductance, determined in amphotericin B permeabilized epithelia. The activity of the high-conductance, Ca2+-activated, voltage-dependent K+ (BK(Ca)) channel, which is primarily responsible for basolateral K+ recycling during Na+ absorption, was inhibited by 10-30 microM quinidine or propafenone in the form of a rapidly dissociating block. Mexiletine and flecainide inhibited the single channel conductance at higher concentrations; disopyramide, lidocaine, and procainamide were ineffective. In conclusion, the present evidence suggests that the diarrhea caused by class I antiarrhythmic drugs such as quinidine and propafenone is a result of a reduction in basolateral K+ conductance and inhibition of BK(Ca) channels, thereby impeding transepithelial Na+ and water absorption.

  6. A novel UV-photolysis approach with acetone and isopropyl alcohol for the rapid determination of fluoride in organofluorine-containing drugs by spectrophotometry

    Directory of Open Access Journals (Sweden)

    Venkata Balarama Krishna Mullapudi

    2018-01-01

    Full Text Available A UV photolysis decomposition (UVPD method for the determination of fluoride in fluorine containing pharmaceuticals by spectrophotometry is reported. It is based on the use of high intensity UV-irradiation in the presence of a digesting solution comprising a mixture of acetone and isopropanol. For the optimization of the UVPD procedure, three bulk drugs (levofloxacin, nebivolol and efavirenz were chosen as representatives of three diverse compounds containing a single fluorine atom, two fluorine atoms, and trifluoromethyl groups respectively. Operational conditions of the UVPD method, such as concentration and volume of reagents (acetone and isopropyl alcohol, and UV irradiation time (1–6 minutes were optimized. The efficiency of digestion was evaluated by the determination of fluoride in sample digests. Using the developed method, it was possible for complete conversion of the organofluoride to free fluoride ion for its subsequent determination by spectrophotometry based on bleaching of Zr–xylenol orange-color complex. Quantitative recovery (>98% of the fluorine in the drug samples could be achieved using a mixture of 2% acetone + 2% isopropyl alcohol + 0.003% Na2CO3 in just 5 minutes of UV irradiation, which can be considered an important aspect considering the difficulties involved in the cleavage of the CF bond. Accuracy was evaluated by comparison of results obtained by the UVPD method with the values estimated using formula weight of the compound and no statistical difference was observed between the results. Therefore, the proposed method is suitable for application in routine analysis of fluoride in organofluorine-containing drugs.

  7. Measuring enzymatic HIV-1 susceptibility to two reverse transcriptase inhibitors as a rapid and simple approach to HIV-1 drug-resistance testing.

    Directory of Open Access Journals (Sweden)

    Dieter Hoffmann

    Full Text Available Simple and cost-effective approaches for HIV drug-resistance testing are highly desirable for managing increasingly expanding HIV-1 infected populations who initiate antiretroviral therapy (ART, particularly in resource-limited settings. Non-nucleoside reverse trancriptase inhibitor (NNRTI-based regimens with an NRTI backbone containing lamivudine (3TC or emtricitabine (FTC are preferred first ART regimens. Failure with these drug combinations typically involves the selection of NNRTI- and/or 3TC/FTC-resistant viruses. Therefore, the availability of simple assays to measure both types of drug resistance is critical. We have developed a high throughput screening test for assessing enzymatic resistance of the HIV-1 RT in plasma to 3TC/FTC and NNRTIs. The test uses the sensitive "Amp-RT" assay with a newly-developed real-time PCR format to screen biochemically for drug resistance in single reactions containing either 3TC-triphosphate (3TC-TP or nevirapine (NVP. Assay cut-offs were defined based on testing a large panel of subtype B and non-subtype B clinical samples with known genotypic profiles. Enzymatic 3TC resistance correlated well with the presence of M184I/V, and reduced NVP susceptibility was strongly associated with the presence of K103N, Y181C/I, Y188L, and G190A/Q. The sensitivity and specificity for detecting resistance were 97.0% and 96.0% in samples with M184V, and 97.4% and 96.2% for samples with NNRTI mutations, respectively. We further demonstrate the utility of an HIV capture method in plasma by using magnetic beads coated with CD44 antibody that eliminates the need for ultracentifugation. Thus our results support the use of this simple approach for distinguishing WT from NNRTI- or 3TC/FTC-resistant viruses in clinical samples. This enzymatic testing is subtype-independent and can assist in the clinical management of diverse populations particularly in resource-limited settings.

  8. Intestinal Water Absorption Varies with Expected Dietary Water Load among Bats but Does Not Drive Paracellular Nutrient Absorption.

    Science.gov (United States)

    Price, Edwin R; Brun, Antonio; Gontero-Fourcade, Manuel; Fernández-Marinone, Guido; Cruz-Neto, Ariovaldo P; Karasov, William H; Caviedes-Vidal, Enrique

    2015-01-01

    Rapid absorption and elimination of dietary water should be particularly important to flying species and were predicted to vary with the water content of the natural diet. Additionally, high water absorption capacity was predicted to be associated with high paracellular nutrient absorption due to solvent drag. We compared the water absorption rates of sanguivorous, nectarivorous, frugivorous, and insectivorous bats in intestinal luminal perfusions. High water absorption rates were associated with high expected dietary water load but were not highly correlated with previously measured rates of (paracellular) arabinose clearance. In conjunction with these tests, we measured water absorption and the paracellular absorption of nutrients in the intestine and stomach of vampire bats using luminal perfusions to test the hypothesis that the unique elongated vampire stomach is a critical site of water absorption. Vampire bats' gastric water absorption was high compared to mice but not compared to their intestines. We therefore conclude that (1) dietary water content has influenced the evolution of intestinal water absorption capacity in bats, (2) solvent drag is not the only driver of paracellular nutrient absorption, and (3) the vampire stomach is a capable but not critical location for water absorption.

  9. Impact of Drug-Rich Colloids of Itraconazole and HPMCAS on Membrane Flux in Vitro and Oral Bioavailability in Rats.

    Science.gov (United States)

    Stewart, Aaron M; Grass, Michael E; Brodeur, Timothy J; Goodwin, Aaron K; Morgen, Michael M; Friesen, Dwayne T; Vodak, David T

    2017-07-03

    Improving the oral absorption of compounds with low aqueous solubility is a common challenge that often requires an enabling technology. Frequently, oral absorption can be improved by formulating the compound as an amorphous solid dispersion (ASD). Upon dissolution, an ASD can reach a higher concentration of unbound drug than the crystalline form, and often generates a large number of sub-micrometer, rapidly dissolving drug-rich colloids. These drug-rich colloids have the potential to decrease the diffusional resistance across the unstirred water layer of the intestinal tract (UWL) by acting as rapidly diffusing shuttles for unbound drug. In a prior study utilizing a membrane flux assay, we demonstrated that, for itraconazole, increasing the concentration of drug-rich colloids increased membrane flux in vitro. In this study, we evaluate spray-dried amorphous solid dispersions (SDDs) of itraconazole with hydroxypropyl methylcellulose acetate succinate (HPMCAS) to study the impact of varying concentrations of drug-rich colloids on the oral absorption of itraconazole in rats, and to quantify their impact on in vitro flux as a function of bile salt concentration. When Sporanox and itraconazole/AFFINISOL High Productivity HPMCAS SDDs were dosed in rats, the maximum absorption rate for each formulation rank-ordered with membrane flux in vitro. The relative maximum absorption rate in vivo correlated well with the in vitro flux measured in 2% SIF (26.8 mM bile acid concentration), a representative bile acid concentration for rats. In vitro it was found that as the bile salt concentration increases, the importance of colloids for improving UWL permeability is diminished. We demonstrate that drug-containing micelles and colloids both contribute to aqueous boundary layer diffusion in proportion to their diffusion coefficient and drug loading. These data suggest that, for compounds with very low aqueous solubility and high epithelial permeability, designing amorphous

  10. A rapid, high-throughput viability assay for Blastocystis spp. reveals metronidazole resistance and extensive subtype-dependent variations in drug susceptibilities.

    Science.gov (United States)

    Mirza, Haris; Teo, Joshua D W; Upcroft, Jacqui; Tan, Kevin S W

    2011-02-01

    Blastocystis is an emerging protistan parasite of controversial pathogenesis. Although metronidazole (Mz) is standard therapy for Blastocystis infections, there have been accumulating reports of treatment failure, suggesting the existence of drug-resistant isolates. Furthermore, very little is known about Blastocystis susceptibility to standard antimicrobials. In the present study, we established resazurin and XTT viability microassays for Blastocystis spp. belonging to subtypes 4 and 7, both of which have been suggested to represent pathogenic zoonotic subtypes. The optimized resazurin assay was used to screen a total of 19 compounds against both subtypes. Interestingly, subtype 7 parasites were resistant to Mz, a 1-position-substituted 5-nitroimidazole (5-NI), while subtype 4 parasites were sensitive. Some cross-resistance was observed to tinidazole, another 1-position 5-NI. Conversely, subtype 4 parasites were resistant to emetine, while subtype 7 parasites were sensitive. Position 2 5-NIs were effective against both subtypes, as were ornidazole, nitazoxanide, furazolidone, mefloquine, quinicrine, quinine, cotrimoxazole (trimethoprim-sulfamethoxazole), and iodoacetamide. Both subtypes were resistant to chloroquine, doxycycline, paromomycin, ampicillin, and pyrimethamine. This is the first study to report extensive variations in drug sensitivities among two clinically important subtypes. Our study highlights the need to reevaluate established treatment regimens for Blastocystis infections and offers clear new treatment options for Mz treatment failures.

  11. A simple and rapid LC-MS/MS method for therapeutic drug monitoring of cetuximab: a GPCO-UNICANCER proof of concept study in head-and-neck cancer patients.

    Science.gov (United States)

    Becher, François; Ciccolini, Joseph; Imbs, Diane-Charlotte; Marin, Clémence; Fournel, Claire; Dupuis, Charlotte; Fakhry, Nicolas; Pourroy, Bertrand; Ghettas, Aurélie; Pruvost, Alain; Junot, Christophe; Duffaud, Florence; Lacarelle, Bruno; Salas, Sebastien

    2017-06-02

    Administration of first-in-class anti-EGFR monoclonal antibody cetuximab is contingent upon extensive pharmacogenomic testing. However in addition to tumor genomics, drug exposure levels could play a critical, yet largely underestimated role, because several reports have demonstrated that cetuximab pharmacokinetic parameters, in particular clearance values, were associated with survival in patients. Here, we have developed an original bioanalytical method based upon the use of LC-MS/MS technology and a simplified sample preparation procedure to assay cetuximab in plasma samples from patients, thus meeting the requirements of standard Therapeutic Drug Monitoring in routine clinical practice. When tested prospectively in a pilot study in 25 head-and-neck cancer patients, this method showed that patients with clinical benefit had cetixumab residual concentrations higher than non-responding patients (i.e., 49 ± 16.3 µg/ml VS. 25.8 ± 17 µg/ml, p < 0.01 t test). Further ROC analysis showed that 33.8 µg/ml was the Cmin threshold predictive of response with an acceptable sensitivity (87%) and specificity (78%). Mass spectrometry-based therapeutic drug monitoring of cetuximab in head-and-neck cancer patients could therefore help to rapidly predict cetuximab efficacy and to adapt dosing if required.

  12. Food and Drug Interactions.

    Science.gov (United States)

    Choi, Jong Hwan; Ko, Chang Mann

    2017-01-01

    Natural foods and vegetal supplements have recently become increasingly popular for their roles in medicine and as staple foods. This has, however, led to the increased risk of interaction between prescribed drugs and the bioactive ingredients contained in these foods. These interactions range from pharmacokinetic interactions (absorption, distribution, metabolism, and excretion influencing blood levels of drugs) to pharmacodynamic interactions (drug effects). In a quantitative respect, these interactions occur mainly during metabolism. In addition to the systemic metabolism that occurs mainly in the liver, recent studies have focused on the metabolism in the gastrointestinal tract endothelium before absorption. Inhibition of metabolism causes an increase in the blood levels of drugs and could have adverse reactions. The food-drug interactions causing increased blood levels of drugs may have beneficial or detrimental therapeutic effects depending on the intensity and predictability of these interactions. It is therefore important to understand the potential interactions between foods and drugs should and the specific outcomes of such interactions.

  13. Rapid, Sensitive, and Accurate Evaluation of Drug Resistant Mutant (NS5A-Y93H Strain Frequency in Genotype 1b HCV by Invader Assay.

    Directory of Open Access Journals (Sweden)

    Satoshi Yoshimi

    Full Text Available Daclatasvir and asunaprevir dual oral therapy is expected to achieve high sustained virological response (SVR rates in patients with HCV genotype 1b infection. However, presence of the NS5A-Y93H substitution at baseline has been shown to be an independent predictor of treatment failure for this regimen. By using the Invader assay, we developed a system to rapidly and accurately detect the presence of mutant strains and evaluate the proportion of patients harboring a pre-treatment Y93H mutation. This assay system, consisting of nested PCR followed by Invader reaction with well-designed primers and probes, attained a high overall assay success rate of 98.9% among a total of 702 Japanese HCV genotype 1b patients. Even in serum samples with low HCV titers, more than half of the samples could be successfully assayed. Our assay system showed a better lower detection limit of Y93H proportion than using direct sequencing, and Y93H frequencies obtained by this method correlated well with those of deep-sequencing analysis (r = 0.85, P <0.001. The proportion of the patients with the mutant strain estimated by this assay was 23.6% (164/694. Interestingly, patients with the Y93H mutant strain showed significantly lower ALT levels (p=8.8 x 10-4, higher serum HCV RNA levels (p=4.3 x 10-7, and lower HCC risk (p=6.9 x 10-3 than those with the wild type strain. Because the method is both sensitive and rapid, the NS5A-Y93H mutant strain detection system established in this study may provide important pre-treatment information valuable not only for treatment decisions but also for prediction of disease progression in HCV genotype 1b patients.

  14. Zeeman atomic absorption spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Hadeishi, T.; McLaughlin, R.

    1978-08-01

    The design and development of a Zeeman atomic absorption spectrometer for trace element analysis are described. An instruction manual is included which details the operation, adjustment, and maintenance. Specifications and circuit diagrams are given. (WHK)

  15. Absorption heat pump system

    Science.gov (United States)

    Grossman, Gershon

    1984-01-01

    The efficiency of an absorption heat pump system is improved by conducting liquid from a second stage evaporator thereof to an auxiliary heat exchanger positioned downstream of a primary heat exchanger in the desorber of the system.

  16. Optical absorption measurement system

    Science.gov (United States)

    Draggoo, Vaughn G.; Morton, Richard G.; Sawicki, Richard H.; Bissinger, Horst D.

    1989-01-01

    The system of the present invention contemplates a non-intrusive method for measuring the temperature rise of optical elements under high laser power optical loading to determine the absorption coefficient. The method comprises irradiating the optical element with a high average power laser beam, viewing the optical element with an infrared camera to determine the temperature across the optical element and calculating the absorption of the optical element from the temperature.

  17. Rapid screening and confirmation of drugs and toxic compounds in biological specimens using liquid chromatography/ion trap tandem mass spectrometry and automated library search.

    Science.gov (United States)

    Liu, Hsiu-Chuan; Liu, Ray H; Lin, Dong-Liang; Ho, Hsiu-O

    2010-01-01

    Recent advances in liquid chromatography/tandem mass spectrometry (LC/MS/MS) technology have provided an opportunity for the development of more specific approaches to achieve the 'screen' and 'confirmation' goals in a single analytical step. For this purpose, this study adapts the electrospray ionization ion trap LC/MS/MS instrumentation (LC/ESI-MS/MS) for the screening and confirmation of over 800 drugs and toxic compounds in biological specimens. Liquid-liquid and solid-phase extraction protocols were coupled to LC/ESI-MS/MS using a 1.8-microm particle size analytical column operated at 50 degrees C. Gradient elution of the analytes was conducted using a solvent system composed of methanol and water containing 0.1% formic acid. Positive-ion ESI-MS/MS spectra and retention times for each of the 800 drugs and toxic compounds were first established using 1-10 microg/mL standard solutions. This spectra and retention time information was then transferred to the library and searched by the identification algorithm for the confirmation of compounds found in test specimens - based on retention time matches and scores of fit, reverse fit, and purity resulting from the searching process. The established method was found highly effective when applied to the analyses of postmortem specimens (blood, urine, and hair) and external proficiency test samples provided by the College of American Pathology (CAP). The development of this approach has significantly improved the efficiency of our routine laboratory operation that was based on a two-step (immunoassay and GC/MS) approach in the past. Copyright 2009 John Wiley & Sons, Ltd.

  18. A rapid and systematic review and economic evaluation of the clinical and cost-effectiveness of newer drugs for treatment of mania associated with bipolar affective disorder.

    Science.gov (United States)

    Bridle, C; Palmer, S; Bagnall, A-M; Darba, J; Duffy, S; Sculpher, M; Riemsma, R

    2004-05-01

    To evaluate the clinical and cost-effectiveness of quetiapine, olanzapine and valproate semisodium in the treatment of mania associated with bipolar disorder. Electronic databases; industry submissions made to the National Institute for Clinical Excellence. Randomised trials and economic evaluations that evaluated the effectiveness of quetiapine, olanzapine or valproate semisodium in the treatment of mania associated with bipolar disorder were selected for inclusion. Data were extracted by one reviewer into a Microsoft Access database and checked for quality and accuracy by a second. The quality of the cost-effectiveness studies was assessed using a checklist updated from that developed by Drummond and colleagues. Relative risk and mean difference data were presented as Forest plots but only pooled where this made sense clinically and statistically. Studies were grouped by drug and, within each drug, by comparator used. Chi-squared tests of heterogeneity were performed for the outcomes if pooling was indicated. A probabilistic model was developed to estimate costs from the perspective of the NHS, and health outcomes in terms of response rate, based on an improvement of at least 50% in a patient's baseline manic symptoms derived from an interview-based mania assessment scale. The model evaluated the cost-effectiveness of the alternative drugs when used as part of treatment for the acute manic episode only. Eighteen randomised trials met the inclusion criteria. Aspects of three of the quetiapine studies were commercial-in-confidence. The quality of the included trials was limited and overall, key methodological criteria were not met in most trials. Quetiapine, olanzapine and valproate semisodium appear superior to placebo in reducing manic symptoms, but may cause side-effects. There appears to be little difference between these treatments and lithium in terms of effectiveness, but quetiapine is associated with somnolence and weight gain, whereas lithium is associated

  19. Drug release, preclinical and clinical pharmacokinetics relationships of alginate pellets prepared by melt technology.

    Science.gov (United States)

    Bose, Anirbandeep; Harjoh, Nurulaini; Pal, Tapan Kumar; Dan, Shubhasis; Wong, Tin Wui

    2016-01-01

    Alginate pellets prepared by the aqueous agglomeration technique experience fast drug dissolution due to the porous pre-formed calcium alginate microstructure. This study investigated in vitro drug release, preclinical and clinical pharmacokinetics relationships of intestinal-specific calcium acetate-alginate pellets against calcium-free and calcium carbonate-alginate pellets. Alginate pellets were prepared by solvent-free melt pelletization instead of aqueous agglomeration technique using chlorpheniramine maleate as model drug. A fast in situ calcium acetate dissolution in pellets resulted in rapid pellet breakup, soluble Ca(2+) crosslinking of alginate fragments and drug dissolution retardation at pH 1.2, which were not found in other pellet types. The preclinical drug absorption rate was lower with calcium acetate loaded than calcium-free alginate pellets. In human subjects, however, the extent and the rate of drug absorption were higher from calcium acetate-loaded pellets than calcium-free alginate pellets. The fine, dispersible and weakly gastric mucoadhesive calcium alginate pellets underwent fast human gastrointestinal transit. They released the drug at a greater rate than calcium-free pellets in the intestine, thereby promoting drug bioavailability. Calcium acetate was required as a disintegrant more than as a crosslinking agent clinically to promote pellet fragmentation, fast gastrointestinal transit and drug release in intestinal medium, and intestinal-specific drug bioavailability.

  20. Absorption cooling device. Absorptions-Kuehlvorrichtung

    Energy Technology Data Exchange (ETDEWEB)

    Bourne, J.; Vardi, I.; Kimchi, Y.; Ben-Dror, J.

    1980-03-25

    The invention concerns improvements of absorption refrigerators, where a lithium chloride or lithium bromide/water cycle is used. According to the invention an inner separating or dividing structure between different functional parts of a machine of this type is provided. The structure contains two sections of wall, which are separated from one another by a suitable space, in order to achieve thermal insulation. This air space is provided with an opening in the direction towards the inside of the container and the opening is shielded to prevent the entry of liquids (in liquid or spray form).

  1. Enhanced vaginal drug delivery through the use of hypotonic formulations that induce fluid uptake.

    Science.gov (United States)

    Ensign, Laura M; Hoen, Timothy E; Maisel, Katharina; Cone, Richard A; Hanes, Justin S

    2013-09-01

    Mucosal epithelia use osmotic gradients for fluid absorption and secretion. We hypothesized that administration of hypotonic solutions would induce fluid uptake that could be advantageous for rapidly delivering drugs through mucus to the vaginal epithelium. We found that hypotonic formulations markedly increased the rate at which small molecule drugs and mucoinert nanoparticles (mucus-penetrating particles, or MPP), but not conventional mucoadhesive nanoparticles (CP), reached the vaginal epithelial surface in vivo in mice. Additionally, hypotonic formulations greatly enhanced drug and MPP delivery to the entire epithelial surface, including deep into the vaginal folds (rugae) that drugs or MPP in isotonic formulations failed to reach efficiently. However, hypotonic formulations caused unencapsulated "free" drugs to be drawn through the epithelium, reducing vaginal retention. In contrast, hypotonic formulations caused MPP to accumulate rapidly and uniformly on vaginal surfaces, ideally positioned for localized sustained drug delivery. Using a mouse model of vaginal genital herpes (HSV-2) infection, we found that hypotonic delivery of free drug led to improved immediate protection, but diminished longer-term protection. In contrast, as we previously demonstrated, hypotonic delivery of drug via MPP led to better long-term retention and protection in the vagina. Importantly, we demonstrate that slightly hypotonic formulations provided rapid and uniform delivery of MPP to the entire vaginal surface, thus enabling formulations with minimal risk of epithelial toxicity. Hypotonic formulations for vaginal drug delivery via MPP may significantly improve prevention and treatment of reproductive tract diseases and disorders. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Evaluation of an automated rapid diagnostic assay for detection of Gram-negative bacteria and their drug-resistance genes in positive blood cultures.

    Directory of Open Access Journals (Sweden)

    Masayoshi Tojo

    Full Text Available We evaluated the performance of the Verigene Gram-Negative Blood Culture Nucleic Acid Test (BC-GN; Nanosphere, Northbrook, IL, USA, an automated multiplex assay for rapid identification of positive blood cultures caused by 9 Gram-negative bacteria (GNB and for detection of 9 genes associated with β-lactam resistance. The BC-GN assay can be performed directly from positive blood cultures with 5 minutes of hands-on and 2 hours of run time per sample. A total of 397 GNB positive blood cultures were analyzed using the BC-GN assay. Of the 397 samples, 295 were simulated samples prepared by inoculating GNB into blood culture bottles, and the remaining were clinical samples from 102 patients with positive blood cultures. Aliquots of the positive blood cultures were tested by the BC-GN assay. The results of bacterial identification between the BC-GN assay and standard laboratory methods were as follows: Acinetobacter spp. (39 isolates for the BC-GN assay/39 for the standard methods, Citrobacter spp. (7/7, Escherichia coli (87/87, Klebsiella oxytoca (13/13, and Proteus spp. (11/11; Enterobacter spp. (29/30; Klebsiella pneumoniae (62/72; Pseudomonas aeruginosa (124/125; and Serratia marcescens (18/21; respectively. From the 102 clinical samples, 104 bacterial species were identified with the BC-GN assay, whereas 110 were identified with the standard methods. The BC-GN assay also detected all β-lactam resistance genes tested (233 genes, including 54 bla(CTX-M, 119 bla(IMP, 8 bla(KPC, 16 bla(NDM, 24 bla(OXA-23, 1 bla(OXA-24/40, 1 bla(OXA-48, 4 bla(OXA-58, and 6 blaVIM. The data shows that the BC-GN assay provides rapid detection of GNB and β-lactam resistance genes in positive blood cultures and has the potential to contributing to optimal patient management by earlier detection of major antimicrobial resistance genes.

  3. Evaluation of an automated rapid diagnostic assay for detection of Gram-negative bacteria and their drug-resistance genes in positive blood cultures.

    Science.gov (United States)

    Tojo, Masayoshi; Fujita, Takahiro; Ainoda, Yusuke; Nagamatsu, Maki; Hayakawa, Kayoko; Mezaki, Kazuhisa; Sakurai, Aki; Masui, Yoshinori; Yazaki, Hirohisa; Takahashi, Hiroshi; Miyoshi-Akiyama, Tohru; Totsuka, Kyoichi; Kirikae, Teruo; Ohmagari, Norio

    2014-01-01

    We evaluated the performance of the Verigene Gram-Negative Blood Culture Nucleic Acid Test (BC-GN; Nanosphere, Northbrook, IL, USA), an automated multiplex assay for rapid identification of positive blood cultures caused by 9 Gram-negative bacteria (GNB) and for detection of 9 genes associated with β-lactam resistance. The BC-GN assay can be performed directly from positive blood cultures with 5 minutes of hands-on and 2 hours of run time per sample. A total of 397 GNB positive blood cultures were analyzed using the BC-GN assay. Of the 397 samples, 295 were simulated samples prepared by inoculating GNB into blood culture bottles, and the remaining were clinical samples from 102 patients with positive blood cultures. Aliquots of the positive blood cultures were tested by the BC-GN assay. The results of bacterial identification between the BC-GN assay and standard laboratory methods were as follows: Acinetobacter spp. (39 isolates for the BC-GN assay/39 for the standard methods), Citrobacter spp. (7/7), Escherichia coli (87/87), Klebsiella oxytoca (13/13), and Proteus spp. (11/11); Enterobacter spp. (29/30); Klebsiella pneumoniae (62/72); Pseudomonas aeruginosa (124/125); and Serratia marcescens (18/21); respectively. From the 102 clinical samples, 104 bacterial species were identified with the BC-GN assay, whereas 110 were identified with the standard methods. The BC-GN assay also detected all β-lactam resistance genes tested (233 genes), including 54 bla(CTX-M), 119 bla(IMP), 8 bla(KPC), 16 bla(NDM), 24 bla(OXA-23), 1 bla(OXA-24/40), 1 bla(OXA-48), 4 bla(OXA-58), and 6 blaVIM. The data shows that the BC-GN assay provides rapid detection of GNB and β-lactam resistance genes in positive blood cultures and has the potential to contributing to optimal patient management by earlier detection of major antimicrobial resistance genes.

  4. Rapid detection of Gram-negative bacteria and their drug resistance genes from positive blood cultures using an automated microarray assay.

    Science.gov (United States)

    Han, Eunhee; Park, Dong-Jin; Kim, Yukyoung; Yu, Jin Kyung; Park, Kang Gyun; Park, Yeon-Joon

    2015-03-01

    We evaluated the performance of the Verigene Gram-negative blood culture (BC-GN) assay (CE-IVD version) for identification of Gram-negative (GN) bacteria and detection of resistance genes. A total of 163 GN organisms (72 characterized strains and 91 clinical isolates from 86 patients) were tested; among the clinical isolates, 86 (94.5%) isolates were included in the BC-GN panel. For identification, the agreement was 98.6% (146/148, 95% confidence interval [CI], 92.1-100) and 70% (7/10, 95% CI, 53.5-100) for monomicrobial and polymicrobial cultures, respectively. Of the 48 resistance genes harbored by 43 characterized strains, all were correctly detected. Of the 19 clinical isolates harboring resistance genes, 1 CTX-M-producing Escherichia coli isolated in polymicrobial culture was not detected. Overall, BC-GN assay provides acceptable accuracy for rapid identification of Gram-negative bacteria and detection of resistance genes, compared with routine laboratory methods despite that it has limitations in the number of genus/species and resistance gene included in the panel and it shows lower sensitivity in polymicrobial cultures. Copyright © 2015. Published by Elsevier Inc.

  5. Ensembling and filtering: an effective and rapid in silico multitarget drug-design strategy to identify RIPK1 and RIPK3 inhibitors.

    Science.gov (United States)

    Fayaz, S M; Rajanikant, G K

    2015-12-01

    Necroptosis, a programmed necrosis pathway, is witnessed in diverse human diseases and is primarily regulated by receptor-interacting serine/threonine protein kinase 1 (RIPK1) and RIPK3. Ablation or inhibition of these individual proteins, or both, has been shown to be protective in various in vitro and in vivo disease models involving necroptosis. In this study, we propose an effective and rapid virtual screening strategy to identify multitarget inhibitors of both RIPK1 and RIPK3. It involves ensemble pharmacophore-based screening (EPS) of a compound database, post-EPS filtration (PEPSF) of the ligand hits, and multiple dockings. Structurally diverse inhibitors were identified through ensemble pharmacophore features, and the speed of this process was enhanced by filtering out the compounds containing cross-features. The stability of these inhibitors with both of the proteins was verified by means of molecular dynamics (MD) simulation. Graphical Abstract A generalized workflow employed in this study. Subsequent utilization of EPS and PEPSF might lead to reduced computational time and load.

  6. Methodology for Rapid Measures of Glutamate Release in Rat Brain Slices Using Ceramic-Based Microelectrode Arrays: Basic Characterization and Drug Pharmacology

    Science.gov (United States)

    Quintero, Jorge E.; Pomerleau, François; Huettl, Peter; Johnson, Kirk W.; Offord, James; Gerhardt, Greg A.

    2011-01-01

    Excessive excitability or hyperexcitability of glutamate-containing neurons in the brain has been proposed as a possible explanation for anxiety, stress-induced disorders, epilepsy, and some neurodegenerative diseases. However, direct measurement of glutamate on a rapid time scale has proven to be difficult. Here we adapted enzyme-based microelectrode arrays (MEA) capable of detecting glutamate in vivo, to assess the effectiveness of hyperexcitability modulators on glutamate release in brain slices of the rat neocortex. Using glutamate oxidase coated ceramic MEAs coupled with constant voltage amperometry, we measured resting glutamate levels and synaptic overflow of glutamate after K+ stimulation in brain slices. MEAs reproducibly detected glutamate on a second-by-second time scale in the brain slice preparation after depolarization with high K+ to evoke glutamate release. This stimulus-evoked glutamate release was robust, reproducible, and calcium dependent. The K+-evoked glutamate release was modulated by ligands to the a2δ subunit of voltage sensitive calcium channels (PD-0332334 and PD-0200390). Meanwhile, agonists to Group II metabotropic glutamate (mGlu) receptors (LY379268 and LY354740), which are known to alter hyperexcitability of glutamate neurons, attenuated K+-evoked glutamate release but did not alter resting glutamate levels. This new MEA technology provides a means of directly measuring the chemical messengers involved in glutamate neurotransmission and thereby helping to reveal the role multiple glutamatergic system components have on glutamate signaling. PMID:21664606

  7. Electromembrane-surrounded solid-phase microextraction coupled to ion mobility spectrometry for the determination of nonsteroidal anti-inflammatory drugs: A rapid screening method in complicated matrices.

    Science.gov (United States)

    Abedi, Hamid; Ebrahimzadeh, Homeira

    2015-05-01

    A new robust method of electromembrane-surrounded solid-phase microextraction coupled to ion mobility mass spectrometry was applied for nonsteroidal anti-inflammatory drugs determination in complex matrices. This is the first time that a graphene/polyaniline composite coating is applied in electromembrane-surrounded solid-phase microextraction method. The homemade graphene/polyaniline composite is characterized by a high electrical conductivity and thermal stability. The variables affecting electromembrane-surrounded solid-phase microextraction, including extraction time; applied voltage and pH were optimized through chemometric methods, central composite design, and response surface methodology. Under the optimized conditions, limits of detection of 0.04 and 0.05 ng/mL were obtained for mefenamic acid and ibuprofen, respectively. The feasibility of electromembrane-surrounded solid-phase microextraction followed by ion mobility mass spectrometry was successfully confirmed by the extraction and determination of low levels of ibuprofen and mefenamic acid in human urine and plasma samples and satisfactory results were obtained. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Evaluation of Microscopic Observation Drug Susceptibility (MODS) and the string test for rapid diagnosis of pulmonary tuberculosis in HIV/AIDS patients in Bolivia.

    Science.gov (United States)

    Lora, Meredith H; Reimer-McAtee, Melissa J; Gilman, Robert H; Lozano, Daniel; Saravia, Ruth; Pajuelo, Monica; Bern, Caryn; Castro, Rosario; Espinoza, Magaly; Vallejo, Maya; Solano, Marco; Challapa, Roxana; Torrico, Faustino

    2015-06-06

    Tuberculosis (TB) is the most common opportunistic infection and the leading cause of death in HIV-positive people worldwide. Diagnosing TB is difficult, and is more challenging in resource-scarce settings where culture-based diagnostic methods rely on poorly sensitive smear microscopy by Ziehl-Neelsen stain (ZN). We performed a cross-sectional study examining the diagnostic utility of Microscopic Observation Drug Susceptibility liquid culture (MODS) versus traditional Ziehl-Neelsen staining (ZN) and Lowenstein Jensen culture (LJ) of pulmonary tuberculosis (TB) and multidrug-resistant tuberculosis (MDRTB) in HIV-infected patients in Bolivia. For sputum scarce individuals we assessed the value of the string test and induced sputum for TB diagnosis. The presence of Mycobacterium tuberculosis (Mtb) in the sputum of 107 HIV-positive patients was evaluated by ZN, LJ, and MODS. Gastric secretion samples obtained by the string test were evaluated by MODS in 102 patients. The TB-HIV co-infection rate of HIV patients with respiratory symptoms by sputum sample was 45 % (48/107); 46/48 (96 %) were positive by MODS, 38/48 (79 %) by LJ, and 30/48 (63 %) by ZN. The rate of MDRTB was 9 % (4/48). Median time to positive culture was 10 days by MODS versus 34 days by LJ (p Bolivia.

  9. Advances in Polymer Design for Enhancing Oral Drug Solubility and Delivery.

    Science.gov (United States)

    Ting, Jeffrey M; Porter, William W; Mecca, Jodi M; Bates, Frank S; Reineke, Theresa M

    2018-01-10

    Synthetic polymers have enabled amorphous solid dispersions (ASDs) to emerge as an oral delivery strategy for overcoming poor drug solubility in aqueous environments. Modern ASD products noninvasively treat a range of chronic diseases (for example, hepatitis C, cystic fibrosis, and HIV). In such formulations, polymeric carriers generate and maintain drug supersaturation upon dissolution, increasing the apparent drug solubility to enhance gastrointestinal barrier absorption and oral bioavailability. In this Review, we outline several approaches in designing polymeric excipients to drive interactions with active pharmaceutical ingredients (APIs) in spray-dried ASDs, highlighting polymer-drug formulation guidelines from industrial and academic perspectives. Special attention is given to new commercial and specialized polymer design strategies that can solubilize highly hydrophobic APIs and suppress the propensity for rapid drug recrystallization. These molecularly customized excipients and hierarchical excipient assemblies are promising toward informing early-stage drug-discovery development and reformulating existing API candidates into potentially lifesaving oral medicines for our growing global population.

  10. Computational drug design strategies applied to the modelling of human immunodeficiency virus-1 reverse transcriptase inhibitors

    Directory of Open Access Journals (Sweden)

    Lucianna Helene Santos

    2015-11-01

    Full Text Available Reverse transcriptase (RT is a multifunctional enzyme in the human immunodeficiency virus (HIV-1 life cycle and represents a primary target for drug discovery efforts against HIV-1 infection. Two classes of RT inhibitors, the nucleoside RT inhibitors (NRTIs and the nonnucleoside transcriptase inhibitors are prominently used in the highly active antiretroviral therapy in combination with other anti-HIV drugs. However, the rapid emergence of drug-resistant viral strains has limited the successful rate of the anti-HIV agents. Computational methods are a significant part of the drug design process and indispensable to study drug resistance. In this review, recent advances in computer-aided drug design for the rational design of new compounds against HIV-1 RT using methods such as molecular docking, molecular dynamics, free energy calculations, quantitative structure-activity relationships, pharmacophore modelling and absorption, distribution, metabolism, excretion and toxicity prediction are discussed. Successful applications of these methodologies are also highlighted.

  11. Central cooling: absorptive chillers

    Energy Technology Data Exchange (ETDEWEB)

    Christian, J.E.

    1977-08-01

    This technology evaluation covers commercially available single-effect, lithium-bromide absorption chillers ranging in nominal cooling capacities of 3 to 1,660 tons and double-effect lithium-bromide chillers from 385 to 1,060 tons. The nominal COP measured at operating conditions of 12 psig input steam for the single-effect machine, 85/sup 0/ entering condenser water, and 44/sup 0/F exiting chilled-water, ranges from 0.6 to 0.65. The nominal COP for the double-effect machine varies from 1.0 to 1.15 with 144 psig entering steam. Data are provided to estimate absorption-chiller performance at off-nominal operating conditions. The part-load performance curves along with cost estimating functions help the system design engineer select absorption equipment for a particular application based on life-cycle costs. Several suggestions are offered which may be useful for interfacing an absorption chiller with the remaining Integrated Community Energy System. The ammonia-water absorption chillers are not considered to be readily available technology for ICES application; therefore, performance and cost data on them are not included in this evaluation.

  12. RAPID3? Aptly named!

    Science.gov (United States)

    Berthelot, J-M

    2014-01-01

    The RAPID3 score is the sum of three 0-10 patient self-report scores: pain, functional impairment on MDHAQ, and patient global estimate. It requires 5 seconds for scoring and can be used in all rheumatologic conditions, although it has mostly been used in rheumatoid arthritis where cutoffs for low disease activity (12/30) have been set. A RAPID3 score of ≤ 3/30 with 1 or 0 swollen joints (RAPID3 ≤ 3 + ≤ SJ1) provides remission criteria comparable to Boolean, SDAI, CDAI, and DAS28 remission criteria, in far less time than a formal joint count. RAPID3 performs as well as the DAS28 in separating active drugs from placebos in clinical trials. RAPID3 also predicts subsequent structural disease progression. RAPID3 can be determined at short intervals at home, allowing the determination of the area under the curve of disease activity between two visits and flare detection. However, RAPID3 should not be seen as a substitute for DAS28 and face to face visits in routine care. Monitoring patient status with only self-report information without a rheumatologist's advice (including joints and physical examination, and consideration of imaging and laboratory tests) may indeed be as undesirable for most patients than joint examination without a patient questionnaire. Conversely, combining the RAPID3 and the DAS28 may consist in faster or more sensitive confirmation that a medication is effective. Similarly, better enquiring of most important concerns of patients (pain, functional status and overall opinion on their disorder) should reinforces patients' confidence in their rheumatologist and treatments.

  13. Pharmacokinetic Modeling of Absorption Behavior of 9-Aminocamptothecin (9-AC) Released from Colon-specific HPMA Copolymer–9-AC Conjugate in Rats

    Science.gov (United States)

    Gao, Song-Qi; Sun, Yongen; Kopečková, Pavla; Peterson, C. Matthew; Kopeček, Jindřich

    2011-01-01

    Purpose To quantitate and predict colon-specific 9-aminocamptothecin (9-AC) release from the N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer–9-AC conjugate and its absorption behavior after oral administration in rats. Methods Drug distribution in the gastrointestinal (GI) tract and the plasma concentration-time profile of 9-AC released from the HPMA copolymer conjugate were predicted using the degradation, transit, and absorption rate constants in cecum. The fate of 9-AC in cecum and liver was measured by in-situ cecum absorption and liver perfusion. Results Following oral administration of the conjugate, 9-AC was released rapidly in cecum. Based on the pharmacokinetic model, up to 60% of the dose was in the cecum at ∼6 h, and 7% of the dose still remained there at 24 h. The predicted plasma concentration curve for released 9-AC after an oral dose of 3 mg/kg of 9-AC equivalent increased gradually and reached a peak of 98 nM at 7 h, then started decreasing slowly to 16 nM at 24 h. The bioavailability value was estimated as 0.31 after the first-pass elimination. Conclusions A pharmacokinetic model delineated the impact of GI transit, drug absorption rate, and first-pass metabolism on drug disposition following oral administration of HPMA copolymer–9-AC conjugate in rats. PMID:17929146

  14. Food and Drug Interactions

    OpenAIRE

    Choi, Jong Hwan; Ko, Chang Mann

    2017-01-01

    Natural foods and vegetal supplements have recently become increasingly popular for their roles in medicine and as staple foods. This has, however, led to the increased risk of interaction between prescribed drugs and the bioactive ingredients contained in these foods. These interactions range from pharmacokinetic interactions (absorption, distribution, metabolism, and excretion influencing blood levels of drugs) to pharmacodynamic interactions (drug effects). In a quantitative respect, these...

  15. Rapid decline in HCV incidence among people who inject drugs associated with national scale-up in coverage of a combination of harm reduction interventions.

    Science.gov (United States)

    Palmateer, Norah E; Taylor, Avril; Goldberg, David J; Munro, Alison; Aitken, Celia; Shepherd, Samantha J; McAllister, Georgina; Gunson, Rory; Hutchinson, Sharon J

    2014-01-01

    Government policy has precipitated recent changes in the provision of harm reduction interventions - injecting equipment provision (IEP) and opiate substitution therapy (OST) - for people who inject drugs (PWID) in Scotland. We sought to examine the potential impact of these changes on hepatitis C virus (HCV) transmission among PWID. We used a framework to triangulate different types of evidence: 'group-level/ecological' and 'individual-level'. Evidence was primarily generated from bio-behavioural cross-sectional surveys of PWID, undertaken during 2008-2012. Individuals in the window period (1-2 months) where the virus is present, but antibodies have not yet been formed, were considered to have recent infection. The survey data were supplemented with service data on the provision of injecting equipment and OST. Ecological analyses examined changes in intervention provision, self-reported intervention uptake, self-reported risk behaviour and HCV incidence; individual-level analyses investigated relationships within the pooled survey data. Nearly 8,000 PWID were recruited in the surveys. We observed a decline in HCV incidence, per 100 person-years, from 13.6 (95% CI: 8.1-20.1) in 2008-09 to 7.3 (3.0-12.9) in 2011-12; a period during which increases in the coverage of OST and IEP, and decreases in the frequency of injecting and sharing of injecting equipment, were observed. Individual-level evidence demonstrated that combined high coverage of needles/syringes and OST were associated with reduced risk of recent HCV in analyses that were unweighted (AOR 0.29, 95%CI 0.11-0.74) and weighted for frequency of injecting (AORw 0.05, 95%CI 0.01-0.18). We estimate the combination of harm reduction interventions may have averted 1400 new HCV infections during 2008-2012. This is the first study to demonstrate that impressive reductions in HCV incidence can be achieved among PWID over a relatively short time period through high coverage of a combination of interventions.

  16. Rapid decline in HCV incidence among people who inject drugs associated with national scale-up in coverage of a combination of harm reduction interventions.

    Directory of Open Access Journals (Sweden)

    Norah E Palmateer

    Full Text Available BACKGROUND: Government policy has precipitated recent changes in the provision of harm reduction interventions - injecting equipment provision (IEP and opiate substitution therapy (OST - for people who inject drugs (PWID in Scotland. We sought to examine the potential impact of these changes on hepatitis C virus (HCV transmission among PWID. METHODS AND FINDINGS: We used a framework to triangulate different types of evidence: 'group-level/ecological' and 'individual-level'. Evidence was primarily generated from bio-behavioural cross-sectional surveys of PWID, undertaken during 2008-2012. Individuals in the window period (1-2 months where the virus is present, but antibodies have not yet been formed, were considered to have recent infection. The survey data were supplemented with service data on the provision of injecting equipment and OST. Ecological analyses examined changes in intervention provision, self-reported intervention uptake, self-reported risk behaviour and HCV incidence; individual-level analyses investigated relationships within the pooled survey data. Nearly 8,000 PWID were recruited in the surveys. We observed a decline in HCV incidence, per 100 person-years, from 13.6 (95% CI: 8.1-20.1 in 2008-09 to 7.3 (3.0-12.9 in 2011-12; a period during which increases in the coverage of OST and IEP, and decreases in the frequency of injecting and sharing of injecting equipment, were observed. Individual-level evidence demonstrated that combined high coverage of needles/syringes and OST were associated with reduced risk of recent HCV in analyses that were unweighted (AOR 0.29, 95%CI 0.11-0.74 and weighted for frequency of injecting (AORw 0.05, 95%CI 0.01-0.18. We estimate the combination of harm reduction interventions may have averted 1400 new HCV infections during 2008-2012. CONCLUSIONS: This is the first study to demonstrate that impressive reductions in HCV incidence can be achieved among PWID over a relatively short time period through

  17. Absorption heat pump system

    Science.gov (United States)

    Grossman, Gershon; Perez-Blanco, Horacio

    1984-01-01

    An improvement in an absorption heat pump cycle is obtained by adding adiabatic absorption and desorption steps to the absorber and desorber of the system. The adiabatic processes make it possible to obtain the highest temperature in the absorber before any heat is removed from it and the lowest temperature in the desorber before heat is added to it, allowing for efficient utilization of the thermodynamic availability of the heat supply stream. The improved system can operate with a larger difference between high and low working fluid concentrations, less circulation losses, and more efficient heat exchange than a conventional system.

  18. 21 CFR 862.2850 - Atomic absorption spectrophotometer for clinical use.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Atomic absorption spectrophotometer for clinical... Laboratory Instruments § 862.2850 Atomic absorption spectrophotometer for clinical use. (a) Identification. An atomic absorption spectrophotometer for clinical use is a device intended to identify and measure...

  19. Visual Absorption Capability

    Science.gov (United States)

    Lee Anderson; Jerry Mosier; Geoffrey Chandler

    1979-01-01

    Visual absorption capability (VAC) is a tool to assess a landscape's susceptibility to visual change caused by man's activities. This paper explores different descriptive approaches to VAC and addresses in depth the development of the VAC process used on the Klamath National Forest. Four biophysical factors were selected to assess VAC for the lands within the...

  20. Chemical Absorption Materials

    DEFF Research Database (Denmark)

    Thomsen, Kaj

    2011-01-01

    Chemical absorption materials that potentially can be used for post combustion carbon dioxide capture are discussed. They fall into five groups, alkanolamines, alkali carbonates, ammonia, amino acid salts, and ionic liquids. The chemistry of the materials is discussed and advantages and drawbacks...

  1. Development of a Novel Oral Cavity Compartmental Absorption and Transit Model for Sublingual Administration: Illustration with Zolpidem

    National Research Council Canada - National Science Library

    Xia, Binfeng; Yang, Zhen; Zhou, Haiying; Lukacova, Viera; Zhu, Wei; Milewski, Mikolaj; Kesisoglou, Filippos

    2015-01-01

    ...™ Oral Cavity Compartmental Absorption and Transit (OCCAT™) model was used to simulate the plasma concentration versus time profiles and the fraction and rate of intraoral drug transit/absorption for Intermezzo...

  2. Multi-class, multi-residue analysis of trace veterinary drugs in milk by rapid screening and quantification using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry.

    Science.gov (United States)

    Zhang, Yaqian; Li, Xiang; Liu, Xiaomao; Zhang, Jinjie; Cao, Yanzhong; Shi, Zhihong; Sun, Hanwen

    2015-12-01

    A simple and rapid multi-class multi-residue analytical method was developed for the screening and quantification of veterinary drugs in milk by ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS). A total of 90 veterinary drugs investigated belonged to almost 20 classes including lincomycins, macrolides, sulfonamides, quinolones, tetracyclines, β-agonists, β-lactams, sedatives, β-receptor antagonists, sex hormones, glucocorticoids, nitroimidazoles, benzimidazoles, nitrofurans, and some others. A modified quick, easy, cheap, effective, rugged, and safe (QuEChERS) procedure was developed for the sample preparation without the solid-phase extraction step. The linearity, sensitivity, accuracy, repeatability, and reproducibility of the method were fully validated. The response of the detector was linear for each target compound in a wide concentration range with a correlation coefficient (R(2)) of 0.9973 to 0.9999 (among them R(2)>0.999 for 73 of 90 analytes). The range of the limit of quantification for these compounds in the milk ranged from 0.10 to 17.30μg/kg. The repeatability and reproducibility were in the range of 2.11 to 9.62% and 2.76 to 13.9%, respectively. The average recoveries ranged from 72.62 to 122.2% with the RSD (n=6) of 1.30 to 9.61% at 3 concentration levels. For the screening method, the data of the precursor and product ions of the target analytes were simultaneously acquired under the all ions MS/MS mode in a single run. An accurate mass database for the confirmation and identification of the target compounds was established. The applicability of the screening method was verified by applying to real milk samples. The proposed analytical method allows the identification and confirmation of the target veterinary drugs at trace levels employing quick analysis time. Certain veterinary drugs were detected in some cases. Copyright © 2015 American Dairy Science Association. Published by

  3. Co-drug strategy for promoting skin targeting and minimizing the transdermal diffusion of hydroquinone and tranexamic acid.

    Science.gov (United States)

    Hsieh, Pei-Wen; Chen, Wei-Yu; Aljuffali, Ibrahim A; Chen, Chun-Che; Fang, Jia-You

    2013-01-01

    Hydroquinone and tranexamic acids (TXA) are skin-lightening agents with a hydrophilic nature and low skin absorption. A high dose is needed for clinical use, resulting in a high incidence of skin irritation. Co-drugs formed by conjugating hydroquinone and TXA were synthesized and their in vitro and in vivo skin absorption characteristics were evaluated. The two synthesized co-drugs were 4-hydroxyphenyl 4-(aminomethyl)cyclohexanecarboxylate (HAC) and 1,4- phenylene bis(aminomethyl)cyclohexanecarboxylate (BAC). The co-drugs were chemically stable in aqueous solution, but rapidly degraded to the respective parent drug in esterases and skin homogenates. Compared to hydroquinone application, 7.2- and 2.4-fold increments in the hydroquinone skin deposition were obtained with the in vitro application of HAC and BAC. HAC and BAC led to 3- and 2-fold enhancements of equivalent TXA deposition compared to TXA administration. The in vivo experiment showed a further enhancement of co-drugs compared to the in vitro setup. The transdermal penetration of co-drugs, especially BAC, was much lower than that of hydroquinone and TXA. This indicated high-level skin targeting by the co-drugs. HAC and BAC revealed strong affinities for the viable epidermis/dermis. Hair follicles are important reservoirs for co-drug delivery. Daily administration of co-drugs to the skin did not generate irritation for up to 7 days. Both co-drugs are superior candidates for treating skin hyperpigmentation.

  4. Temperature measurements via narrow line laser absorption of carbon dioxide

    Energy Technology Data Exchange (ETDEWEB)

    Wooldridge, M.S. [Texas A and M Univ., College Station, TX (United States). Dept. of Mechanical Engineering

    1996-12-31

    Theoretical development for temperature measurements via narrow line, infrared absorption of carbon dioxide (CO{sub 2}) is presented. The proposed technique is based on rapid-scanning of two adjacent absorption line shapes. Spectroscopic considerations for sensitivity to temperature measurements are discussed. Several line pairs are evaluated, and the R(58) and R(60) transitions of the (00{sup 0}1){l_arrow}(00{sup 0}0) band are suggested for use in high temperature measurements for combustion systems.

  5. Rapid Prototyping

    Science.gov (United States)

    1999-01-01

    Javelin, a Lone Peak Engineering Inc. Company has introduced the SteamRoller(TM) System as a commercial product. The system was designed by Javelin during a Phase II NASA funded small commercial product. The purpose of the invention was to allow automated-feed of flexible ceramic tapes to the Laminated Object Manufacturing rapid prototyping equipment. The ceramic material that Javelin was working with during the Phase II project is silicon nitride. This engineered ceramic material is of interest for space-based component.

  6. Evaluation of two line probe assays for rapid detection of Mycobacterium tuberculosis, tuberculosis (TB) drug resistance, and non-TB Mycobacteria in HIV-infected individuals with suspected TB.

    Science.gov (United States)

    Luetkemeyer, Anne F; Kendall, Michelle A; Wu, Xingye; Lourenço, Maria Cristina; Jentsch, Ute; Swindells, Susan; Qasba, Sarojini S; Sanchez, Jorge; Havlir, Diane V; Grinsztejn, Beatriz; Sanne, Ian M; Firnhaber, Cynthia

    2014-04-01

    Limited performance data from line probe assays (LPAs), nucleic acid tests used for the rapid diagnosis of tuberculosis (TB), nontuberculosis mycobacteria (NTM), and Mycobacterium tuberculosis drug resistance are available for HIV-infected individuals, in whom paucibacillary TB is common. In this study, the strategy of testing sputum with GenoType MTBDRplus (MTBDR-Plus) and GenoType Direct LPA (Direct LPA) was compared to a gold standard of one mycobacterial growth indicator tube (MGIT) liquid culture. HIV-positive (HIV(+)) individuals with suspected TB from southern Africa and South America with tuberculosis culture positive, of which 276 (72.8%) were acid-fast bacillus (AFB) smear positive. MTBDR-Plus had a sensitivity of 81.0% and a specificity of 100%, with sensitivities of 44.1% in AFB smear-negative versus 94.6% in AFB smear-positive specimens. For specimens that were positive for M. tuberculosis by MTBDR-Plus, the sensitivity and specificity for rifampin resistance were 91.7% and 96.6%, respectively, and for isoniazid (INH) they were 70.6% and 99.1%. The Direct LPA had a sensitivity of 88.4% and a specificity of 94.6% for M. tuberculosis detection, with a sensitivity of 72.5% in smear-negative specimens. Ten of 639 MGIT cultures grew Mycobacterium avium complex or Mycobacterium kansasii, half of which were detected by Direct LPA. Both LPA assays performed well in specimens from HIV-infected individuals, including in AFB smear-negative specimens, with 72.5% sensitivity for M. tuberculosis identification with the Direct LPA and 44.1% sensitivity with MTBDR-Plus. LPAs have a continued role for use in settings where rapid identification of INH resistance and clinically relevant NTM are priorities.

  7. Drug: D01662 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available ins 311 Vitamins A and D preparations 3112 Synthetic vitamin D preparations D01662 ...eral absorption Therapeutic category of drugs in Japan [BR:br08301] 3 Agents affecting metabolism 31 Vitam

  8. Drug: D02381 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available member 3 (TAS1R3) agonist [HSA:83756] [KO:K04626] hsa04742(80834+83756) Taste transduction hsa04973(80834+83756) Carbohydrate digest...ion and absorption Target-based classification of drugs

  9. Drug: D01098 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available 1] [KO:K08539] hsa04961(7421) Endocrine and other factor-regulated calcium reabsorption... hsa04978(7421) Mineral absorption Therapeutic category of drugs in Japan [BR:br08301] 2 Agents affect

  10. Drug: D07578 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available r agonist [HSA:7421] [KO:K08539] hsa04961(7421) Endocrine and other factor-regulated calcium reabsorption hsa04978(7421) Mineral abso...rption map07047 Osteoporosis drugs Therapeutic category

  11. Drug: D00129 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available ceptor agonist [HSA:7421] [KO:K08539] hsa04961(7421) Endocrine and other factor-regulated calcium reabsorption... hsa04978(7421) Mineral absorption map07047 Osteoporosis drugs Therapeutic cate

  12. Drug: D08996 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available nhibitor [HSA:1803] [KO:K01278] hsa04974(1803) Protein digestion and absorption Transporter: ABCB1 [HSA:5243] map07051 Antidiabeti...P drug classification [BR:br08302] Blood Glucose Regulators Antidiabetic Agents S

  13. Drug: D09753 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available Protein digestion and absorption map07051 Antidiabetics Therapeutic category of d...rugs in Japan [BR:br08301] 3 Agents affecting metabolism 39 Other agents affecting metabolism 396 Antidiabeti

  14. Drug: D08107 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available 4600 81579 8399 84647] [KO:K01047] hsa04975(26279+30814+391013+50487+5319+5320+5322+64600+81579+8399+84647) Fat digestion and absorpt...ion Target-based classification of drugs [BR:br08310] En

  15. Drug: D09625 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available t of diabetes [DS:H00409] dipeptidyl-peptidase 4 (DPP4) inhibitor [HSA:1803] [KO:K01278] hsa04974(1803) Protein digestion and absorpt...ion Target-based classification of drugs [BR:br08310] Enzymes Hydrolases dipeptidyl

  16. Revisiting Absorptive Capacity

    DEFF Research Database (Denmark)

    de Araújo, Ana Luiza Lara; Ulhøi, John Parm; Lettl, Christopher

    Absorptive capacity has mostly been perceived as a 'passive' outcome of R&D investments. Recently, however, a growing interest into its 'proactive' potentials has emerged. This paper taps into this development and proposes a dynamic model for conceptualizing the determinants of the complementary ...... processes, with emphasis on exploitative learning. Before concluding, the paper addresses implications for theory and practice and limitations of this study....

  17. Relic Neutrino Absorption Spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Eberle, b

    2004-01-28

    Resonant annihilation of extremely high-energy cosmic neutrinos on big-bang relic anti-neutrinos (and vice versa) into Z-bosons leads to sizable absorption dips in the neutrino flux to be observed at Earth. The high-energy edges of these dips are fixed, via the resonance energies, by the neutrino masses alone. Their depths are determined by the cosmic neutrino background density, by the cosmological parameters determining the expansion rate of the universe, and by the large redshift history of the cosmic neutrino sources. We investigate the possibility of determining the existence of the cosmic neutrino background within the next decade from a measurement of these absorption dips in the neutrino flux. As a by-product, we study the prospects to infer the absolute neutrino mass scale. We find that, with the presently planned neutrino detectors (ANITA, Auger, EUSO, OWL, RICE, and SalSA) operating in the relevant energy regime above 10{sup 21} eV, relic neutrino absorption spectroscopy becomes a realistic possibility. It requires, however, the existence of extremely powerful neutrino sources, which should be opaque to nucleons and high-energy photons to evade present constraints. Furthermore, the neutrino mass spectrum must be quasi-degenerate to optimize the dip, which implies m{sub {nu}} 0.1 eV for the lightest neutrino. With a second generation of neutrino detectors, these demanding requirements can be relaxed considerably.

  18. Absorption Study of Genistein Using Solid Lipid Microparticles and Nanoparticles: Control of Oral Bioavailability by Particle Sizes.

    Science.gov (United States)

    Kim, Jeong Tae; Barua, Sonia; Kim, Hyeongmin; Hong, Seong-Chul; Yoo, Seung-Yup; Jeon, Hyojin; Cho, Yeongjin; Gil, Sangwon; Oh, Kyungsoo; Lee, Jaehwi

    2017-07-01

    In this study, the effect of particle size of genistein-loaded solid lipid particulate systems on drug dissolution behavior and oral bioavailability was investigated. Genistein-loaded solid lipid microparticles and nanoparticles were prepared with glyceryl palmitostearate. Except for the particle size, other properties of genistein-loaded solid lipid microparticles and nanoparticles such as particle composition and drug loading efficiency and amount were similarly controlled to mainly evaluate the effect of different particle sizes of the solid lipid particulate systems on drug dissolution behavior and oral bioavailability. The results showed that genistein-loaded solid lipid microparticles and nanoparticles exhibited a considerably increased drug dissolution rate compared to that of genistein bulk powder and suspension. The microparticles gradually released genistein as a function of time while the nanoparticles exhibited a biphasic drug release pattern, showing an initial burst drug release, followed by a sustained release. The oral bioavailability of genistein loaded in solid lipid microparticles and nanoparticles in rats was also significantly enhanced compared to that in bulk powders and the suspension. However, the bioavailability from the microparticles increased more than that from the nanoparticles mainly because the rapid drug dissolution rate and rapid absorption of genistein because of the large surface area of the genistein-solid lipid nanoparticles cleared the drug to a greater extent than the genistein-solid lipid microparticles did. Therefore, the findings of this study suggest that controlling the particle size of solid-lipid particulate systems at a micro-scale would be a promising strategy to increase the oral bioavailability of genistein.

  19. Absorption in periodic layered structures

    OpenAIRE

    Moroz, Alexander; Tip, Adriaan; Combes, Jean-Michel

    2000-01-01

    Photonic band structure of metal-dielectric and semiconductor-dielectric layered structures are studied in the presence of a strong absorption. It is shown that absorption can enlarge some gaps by as much as 50%.

  20. Colloidal carriers for extended absorption window of furosemide.

    Science.gov (United States)

    Sultan, Amal A; El-Gizawy, Sanaa A; Osman, Mohamed A; El Maghraby, Gamal M

    2016-03-01

    The aim was to investigate the potential of self-microemulsifying drug delivery systems (SMEDDS) and niosomes as carriers for widening the gastrointestinal absorption window of furosemide (model acidic drug). The drug was incorporated in SMEDDS and was encapsulated into niosomes. The intestinal absorption was monitored at two anatomical sites (duodenum and jejuno-ileum). This employed in situ rabbit intestinal perfusion technique. Perfusion of drug solution (control) revealed poor intestinal permeability with per cent fraction absorbed (%Fa) from the duodenum and jejuno-ileum being 1.3 and 0.6 % per cm, respectively. Formulation of furosemide as SMEDDS increased the %Fa from the duodenum and jejuno-ileum to reach 1.7 and 1 % per cm, respectively. Niosomal encapsulation increased the %Fa from duodenum and jejuno-ileum to record 1.9 and 1.2 % per cm, respectively. The increase in the %Fa was also revealed as a reduction in the length required for 95 % absorption of the drug which was reduced from 557.2 to 245.8 cm and to 279.8 cm after delivery as niosomes or SMEDDS, respectively, in case of jejuno-ileum. The same trend was recorded with the duodenum. The recorded results highlighted the potential for SMEDDS and niosomes for widening the absorption window of acidic drugs after oral administration. © 2016 Royal Pharmaceutical Society, Journal of Pharmacy and Pharmacology.

  1. Digital Direct-to-Consumer Advertising: A Perfect Storm of Rapid Evolution and Stagnant Regulation; Comment on “Trouble Spots in Online Direct-to-Consumer Prescription Drug Promotion: A Content Analysis of FDA Warning Letters”

    Directory of Open Access Journals (Sweden)

    Tim K. Mackey

    2016-04-01

    Full Text Available The adoption and use of digital forms of direct-to-consumer advertising (also known as “eDTCA” is on the rise. At the same time, the universe of eDTCA is expanding, as technology on Internet-based platforms continues to evolve, from static websites, to social media, and nearly ubiquitous use of mobile devices. However, little is known about how this unique form of pharmaceutical marketing impacts consumer behavior, public health, and overall healthcare utilization. The study by Kim analyzing US Food and Drug Administration (FDA notices of violations (NOVs and warning letters regarding online promotional activities takes us in the right direction, but study results raise as many questions as it does answers. Chief among these are unanswered concerns about the unique regulatory challenges posed by the “disruptive” qualities of eDTCA, and whether regulators have sufficient resources and oversight powers to proactively address potential violations. Further, the globalization of eDTCA via borderless Internet-based technologies raises larger concerns about the potential global impact of this form of health marketing unique to only the United States and New Zealand. Collectively, these challenges make it unlikely that regulatory science will be able to keep apace with the continued rapid evolution of eDTCA unless more creative policy solutions are explored.

  2. Digital Direct-to-Consumer Advertising: A Perfect Storm of Rapid Evolution and Stagnant Regulation Comment on "Trouble Spots in Online Direct-to-Consumer Prescription Drug Promotion: A Content Analysis of FDA Warning Letters".

    Science.gov (United States)

    Mackey, Tim K

    2016-02-03

    The adoption and use of digital forms of direct-to-consumer advertising (also known as "eDTCA") is on the rise. At the same time, the universe of eDTCA is expanding, as technology on Internet-based platforms continues to evolve, from static websites, to social media, and nearly ubiquitous use of mobile devices. However, little is known about how this unique form of pharmaceutical marketing impacts consumer behavior, public health, and overall healthcare utilization. The study by Kim analyzing US Food and Drug Administration (FDA) notices of violations (NOVs) and warning letters regarding online promotional activities takes us in the right direction, but study results raise as many questions as it does answers. Chief among these are unanswered concerns about the unique regulatory challenges posed by the "disruptive" qualities of eDTCA, and whether regulators have sufficient resources and oversight powers to proactively address potential violations. Further, the globalization of eDTCA via borderless Internet-based technologies raises larger concerns about the potential global impact of this form of health marketing unique to only the United States and New Zealand. Collectively, these challenges make it unlikely that regulatory science will be able to keep apace with the continued rapid evolution of eDTCA unless more creative policy solutions are explored. © 2016 by Kerman University of Medical Sciences.

  3. Subgap Absorption in Conjugated Polymers

    Science.gov (United States)

    Sinclair, M.; Seager, C. H.; McBranch, D.; Heeger, A. J; Baker, G. L.

    1991-01-01

    Along with X{sup (3)}, the magnitude of the optical absorption in the transparent window below the principal absorption edge is an important parameter which will ultimately determine the utility of conjugated polymers in active integrated optical devices. With an absorptance sensitivity of fluorination.

  4. Absorption characteristics of bacteriorhodopsin molecules

    Indian Academy of Sciences (India)

    The analytical expression for the absorption coefficient of BR film is applied to study the absorption characteristics of BR molecules in a typical laser system operating at funda- mental wavelength 514 nm. The experimental data available for the absorption coefficients of the levels B and M corresponding to the wavelength ...

  5. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... WMATA) Dallas Area Rapid Transit (DART) NY Metropolitan Transportation Authority (MTA) Titan Worldwide Hestia International Panasonic Times ... Education Projects National Drug & Alcohol Facts Week NIDA ...

  6. Different mathematical processing of absorption, ratio and derivative spectra for quantification of mixtures containing minor component: An application to the analysis of the recently co-formulated antidiabetic drugs; canagliflozin and metformin

    Science.gov (United States)

    Lotfy, Hayam M.; Mohamed, Dalia; Elshahed, Mona S.

    2018-01-01

    In the presented work several spectrophotometric methods were performed for the quantification of canagliflozin (CGZ) and metformin hydrochloride (MTF) simultaneously in their binary mixture. Two of these methods; response correlation (RC) and advanced balance point-spectrum subtraction (ABP-SS) were developed and introduced for the first time in this work, where the latter method (ABP-SS) was performed on both the zero order and the first derivative spectra of the drugs. Besides, two recently established methods; advanced amplitude modulation (AAM) and advanced absorbance subtraction (AAS) were also accomplished. All the proposed methods were validated in accordance to the ICH guidelines, where all methods were proved to be accurate and precise. Additionally, the linearity range, limit of detection and limit of quantification were determined and the selectivity was examined through the analysis of laboratory prepared mixtures and the combined dosage form of the drugs. The proposed methods were capable of determining the two drugs in the ratio present in the pharmaceutical formulation CGZ:MTF (1:17) without the requirement of any preliminary separation, further dilution or standard spiking. The results obtained by the proposed methods were in compliance with the reported chromatographic method when compared statistically, proving the absence of any significant difference in accuracy and precision between the proposed and reported methods.

  7. Absorption in dielectric models

    CERN Document Server

    Churchill, R J

    2015-01-01

    We develop a classical microscopic model of a dielectric. The model features nonlinear interaction terms between polarizable dipoles and lattice vibrations. The lattice vibrations are found to act as a pseudo-reservoir, giving broadband absorption of electromagnetic radiation without the addition of damping terms in the dynamics. The effective permittivity is calculated using a perturbative iteration method and is found to have the form associated with real dielectrics. Spatial dispersion is naturally included in the model and we also calculate the wavevector dependence of the permittivity.

  8. Time dependent effects of two absorption enhancers on the nasal absorption of growth hormone in rabbits

    DEFF Research Database (Denmark)

    Vermehren, C.; Hansen, Harald S.; Thomsen, M.K.

    1996-01-01

    Enhancer-based drug preparations allow absorption of peptide drugs. We investigated the reversibility with time of nasal absorption of human growth hormone (hGH) induced by the absorption enhancers didecanoylphosphatidylcholine (DDPC) and a-cyclodextrin (a-CD). Rabbits were dosed intranasally...... with enhancer in the absence of hGH at time -3, -1, -0.5 and 0 h. At time zero the same groups of rabbits were dosed with a hGH powder devoid of the enhancers. Values for plasma hGH AUC and C(max) were estimated in order to measure the degree of absorption, and rabbits receiving hGH together with enhancers were...... the tissue. Similar findings were obtained with a-CD alone, whereas a preparation containing only DDPC showed no recovery of leakiness. The effect of a-CD was also investigated in vitro in rabbit nasal mucosa mounted in Ussing chambers. Incubation for 15 min with 1, 3 and 8% a-CD induced a concentration...

  9. Time dependent effects of two absorption enhancers on the nasal absorption of growth hormone in rabbits

    DEFF Research Database (Denmark)

    Vermehren, Charlotte; Hansen, H.S.; Thomsen, M.K.

    1996-01-01

    Enhancer-based drug preparations allow absorption of peptid drugs. We investigated the reversibility with time of nasal absorption of human growth hormone (hGH) induced by the absorption enhancers didecanoylhposphatidylcholine (DDPC) and Ó-cyclodextrin (Ó-CD). Rabbits were dosed intranasally...... with enhancer in the absence of hGH at time -3, -1, -0.5 and 0 h. At time zero the same groups of rabbits were dosed with a hGH powder devoid of the enhancers. Values for plasma hGH AUC and Cmax were estimated in order to measure the degree of absorption, and rabbits receiving hGH together with enhancers were...... the tissue. Similar findings were obtained with Ó-CD alone, whereas a preparation containing only DDPC showed no recovery of leakiness. The effect of Ó-CD was also investigated in vitro in rabbit nasal mucosa mounted in Ussing chambers. Incubation ofr 15 min with 1, 3 and 8% Ó-CD induced a concentration...

  10. Geospatial Absorption and Regional Effects

    Directory of Open Access Journals (Sweden)

    IOAN MAC

    2009-01-01

    Full Text Available The geospatial absorptions are characterized by a specific complexity both in content and in their phenomenological and spatial manifestation fields. Such processes are differentiated according to their specificity to pre-absorption, absorption or post-absorption. The mechanisms that contribute to absorption are extremely numerous: aggregation, extension, diffusion, substitution, resistivity (resilience, stratification, borrowings, etc. Between these mechanisms frequent relations are established determining an amplification of the process and of its regional effects. The installation of the geographic osmosis phenomenon in a given territory (a place for example leads to a homogenization of the geospatial state and to the installation of the regional homogeneity.

  11. Skin absorption through atopic dermatitis skin

    DEFF Research Database (Denmark)

    Halling-Overgaard, A-S; Kezic, S; Jakasa, I

    2017-01-01

    Patients with atopic dermatitis have skin barrier impairment in both lesional and non-lesional skin. They are typically exposed to emollients daily and topical anti-inflammatory medicaments intermittently, hereby increasing the risk of developing contact allergy and systemic exposed to chemicals...... ingredients found in these topical preparations. We systematically searched for studies that investigated skin absorption of various penetrants, including medicaments, in atopic dermatitis patients, but also animals with experimentally induced dermatitis. We identified 40 articles, i.e. 11 human studies...... examining model penetrants, 26 human studies examining atopic dermatitis drugs and 3 animal studies. We conclude that atopic dermatitis patients have nearly two-fold increased skin absorption when compared to healthy controls. There is a need for well-designed epidemiological and dermato...

  12. Drug Facts

    Medline Plus

    Full Text Available ... Why Is It So Hard to Quit Drugs? Effects of Drugs Drug Use and Other People Drug ... Unborn Children Drug Use and Your Health Other Effects on the Body Drug Use Hurts Brains Drug ...

  13. Mucus-penetrating nanoparticles for vaginal and gastrointestinal drug delivery

    Science.gov (United States)

    Ensign-Hodges, Laura

    A method that could provide more uniform and longer-lasting drug delivery to mucosal surfaces holds the potential to greatly improve the effectiveness of prophylactic and therapeutic approaches for numerous diseases and conditions, including sexually transmitted infections and inflammatory bowel disease. However, the body's natural defenses, including adhesive, rapidly cleared mucus linings coating nearly all entry points to the body not covered by skin, has limited the effectiveness of drug and gene delivery by nanoscale delivery systems. Here, we investigate the use of muco-inert mucus-penetrating nanoparticles (MPP) for improving vaginal and gastrointestinal drug delivery. Conventional hydrophobic nanoparticles strongly adhere to mucus, facilitating rapid clearance from the body. Here, we demonstrate that mucoadhesive polystyrene nanoparticles (conventional nanoparticles, CP) become mucus-penetrating in human cervicovaginal mucus (CVM) after pretreatment with sufficient concentrations of Pluronic F127. Importantly, the diffusion rate of large MPP did not change in F127 pretreated CVM, implying there is no affect on the native pore structure of CVM. Additionally, there was no increase in inflammatory cytokine release in the vaginal tract of mice after daily application of 1% F127 for one week. Importantly, HSV virus remains adherent in F127-pretreated CVM. Mucosal epithelia use osmotic gradients for fluid absorption and secretion. We hypothesized that hypotonically-induced fluid uptake could be advantageous for rapidly delivering drugs through mucus to the vaginal epithelium. We evaluated hypotonic formulations for delivering water-soluble drugs and for drug delivery with MPP. Hypotonic formulations markedly increased the rate at which drugs and MPP reached the epithelial surface. Additionally, hypotonic formulations greatly enhanced drug and MPP delivery to the entire epithelial surface, including deep into the vaginal folds (rugae) that isotonic formulations

  14. Buccal absorption of ketobemidone and various ester prodrugs in the rat

    DEFF Research Database (Denmark)

    Hansen, L.B.; Jorgensen, A.; Rasmussen, S.N.

    1992-01-01

    The buccal absorption of ketobemidone, a strong narcotic analgesic, and various carboxylate and carbonate ester prodrugs was studied in rats. The compounds were administered in the form of aqueous solutions of pH 7.4. The absolute bioavailability of ketobemidone following buccal dosing was 26......% whereas the bioavailability of ketobemidone following buccal administration of the prodrugs ranged from 37 to 98%. The highest bioavailability was obtained with the ethyl carbonate ester. An apparent parabolic correlation between bioavailability and lipophilicity of the compounds was seen. All esters were...... rapidly hydrolyzed to ketobemidone after both buccal and intravenous administration. The acute toxicity of the esters after i.v. administration to mice and rats was similar to that of the parent drug. It is concluded that esterification of the phenolic hydroxyl group in ketobemidone to give a more...

  15. Enhancement of absorption and hepatoprotective potential through soya-phosphatidylcholine-andrographolide vesicular system.

    Science.gov (United States)

    Jain, Pushpendra Kumar; Khurana, Navneet; Pounikar, Yogesh; Gajbhiye, Asmita; Kharya, Murli Dhar

    2013-06-01

    Andrographis paniculata is a medicinal herb used extensively for various ailments and contains therapeutically active phytoconstituent, andrographolide (AN). Although hepatoprotective activity of AN is established, but their bioavailability is restricted due to its rapid clearance. The aim of this study, therefore, was to formulate AN herbosomes (ANH) through complexation with naturally occurring soya-phosphatidylcholine (SPC), in order to enhance absorption. Prepared andrographolide-soy phosphatidylcholine (AN-SPC) complex prepared was subjected for characterisation of complex and formation of vesicular system known as ANH using rotary evaporation techniques. This complex was subjected to in vitro study using everted small intestine sac technique which showed significantly increased absorption of AN from the ANH as compared to the plain AN. The hepatoprotective potential of ANH and plain AN was evaluated using carbon tetrachloride inducing hepatotoxicity rat model and compared, in which ANH equivalent to 50 mg/kg of plain AN significantly restore serum glutamate oxalacetate transaminase (112.4 ± 9.67 for AN whereas 90.2 ± 4.23 for ANH) and serum glutamate pyruvate transaminase (109.3 ± 7.89 for AN whereas 90.6 ± 4.34 for ANH) level as compared to control group. The ANH showed significantly better absorption than plain AN and this effect of ANH was also comparable to the standard drug (Silymarin). The findings of present study reveal that ANH has better bioavailability as shown by in vitro absorption study and hence improved hepatoprotection as compared to plain AN at equivalent dose.

  16. Improving uptake and use of malaria rapid diagnostic tests in the context of artemisinin drug resistance containment in eastern Myanmar: an evaluation of incentive schemes among informal private healthcare providers.

    Science.gov (United States)

    Aung, Tin; White, Christopher; Montagu, Dominic; McFarland, Willi; Hlaing, Thaung; Khin, Hnin Su Su; San, Aung Kyaw; Briegleb, Christina; Chen, Ingrid; Sudhinaraset, May

    2015-03-06

    As efforts to contain artemisinin resistance and eliminate Plasmodium falciparum intensify, the accurate diagnosis and prompt effective treatment of malaria are increasingly needed in Myanmar and the Greater Mekong Sub-region (GMS). Rapid diagnostic tests (RDTs) have been shown to be safe, feasible, and effective at promoting appropriate treatment for suspected malaria, which are of particular importance to drug resistance containment. The informal private sector is often the first point of care for fever cases in malaria endemic areas across Myanmar and the GMS, but there is little published information about informal private provider practices, quality of service provision, or potential to contribute to malaria control and elimination efforts. This study tested different incentives to increase RDT use and improve the quality of care among informal private healthcare providers in Myanmar. The study randomized six townships in the Mon and Shan states of rural Myanmar into three intervention arms: 1) RDT price subsidies, 2) price subsidies with product-related financial incentives, and 3) price subsidies with intensified information, education and counselling (IEC). The study assessed the uptake of RDT use in the communities by cross-sectional surveys of 3,150 households at baseline and six months post-intervention (6,400 households total, 832 fever cases). The study also used mystery clients among 171 providers to assess quality of service provision across intervention arms. The pilot intervention trained over 600 informal private healthcare providers. The study found a price subsidy with intensified IEC, resulted in the highest uptake of RDTs in the community, as compared to subsidies alone or merchandise-related financial incentives. Moreover, intensified IEC led to improvements in the quality of care, with mystery client surveys showing almost double the number of correct treatment following diagnostic test results as compared to a simple subsidy. Results show

  17. Sabine absorption coefficients to random incidence absorption coefficients

    DEFF Research Database (Denmark)

    Jeong, Cheol-Ho

    2014-01-01

    into random incidence absorption coefficients for porous absorbers are investigated. Two optimization-based conversion methods are suggested: the surface impedance estimation for locally reacting absorbers and the flow resistivity estimation for extendedly reacting absorbers. The suggested conversion methods......Absorption coefficients measured by the chamber method are referred to as Sabine absorption coefficients, which sometimes exceed unity due to the finite size of a specimen and non-uniform intensity in the test chamber. In this study, several methods that convert Sabine absorption coefficients...

  18. A rapid method for simultaneous detection of phenotypic resistance to inhibitors of protease and reverse transcriptase in recombinant human immunodeficiency virus type 1 isolates from patients treated with antiretroviral drugs.

    Science.gov (United States)

    Hertogs, K; de Béthune, M P; Miller, V; Ivens, T; Schel, P; Van Cauwenberge, A; Van Den Eynde, C; Van Gerwen, V; Azijn, H; Van Houtte, M; Peeters, F; Staszewski, S; Conant, M; Bloor, S; Kemp, S; Larder, B; Pauwels, R

    1998-02-01

    Combination therapy with protease (PR) and reverse transcriptase (RT) inhibitors can efficiently suppress human immunodeficiency virus (HIV) replication, but the emergence of drug-resistant variants correlates strongly with therapeutic failure. Here we describe a new method for high-throughput analysis of clinical samples that permits the simultaneous detection of HIV type 1 (HIV-1) phenotypic resistance to both RT and PR inhibitors by means of recombinant virus assay technology. HIV-1 RNA is extracted from plasma samples, and a 2.2-kb fragment containing the entire HIV-1 PR- and RT-coding sequence is amplified by nested reverse transcription-PCR. The pool of PR-RT-coding sequences is then cotransfected into CD4+ T lymphocytes (MT4) with the pGEMT3deltaPRT plasmid from which most of the PR (codons 10 to 99) and RT (codons 1 to 482) sequences are deleted. Homologous recombination leads to the generation of chimeric viruses containing PR- and RT-coding sequences derived from HIV-1 RNA in plasma. The susceptibilities of the chimeric viruses to all currently available RT and/or PR inhibitors is determined by an MT4 cell-3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide-based cell viability assay in an automated system that allows high sample throughput. The profile of resistance to all RT and PR inhibitors is displayed graphically in a single PR-RT-Antivirogram. This assay system facilitates the rapid large-scale phenotypic resistance determinations for all RT and PR inhibitors in one standardized assay.

  19. Drug: D00625 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available ose metabolism hsa04973(8972) Carbohydrate digestion and absorption map07051 Antidiabetics Therapeutic categ...ory of drugs in Japan [BR:br08301] 3 Agents affecting metabolism 39 Other agents affecting metabolism 396 Antidiabeti...Miglitol (JAN/USAN/INN) USP drug classification [BR:br08302] Blood Glucose Regulators Antidiabeti

  20. X-ray Absorption Spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Yano, Junko; Yachandra, Vittal K.

    2009-07-09

    This review gives a brief description of the theory and application of X-ray absorption spectroscopy, both X-ray absorption near edge structure (XANES) and extended X-ray absorption fine structure (EXAFS), especially, pertaining to photosynthesis. The advantages and limitations of the methods are discussed. Recent advances in extended EXAFS and polarized EXAFS using oriented membranes and single crystals are explained. Developments in theory in understanding the XANES spectra are described. The application of X-ray absorption spectroscopy to the study of the Mn4Ca cluster in Photosystem II is presented.

  1. Drug Facts

    Medline Plus

    Full Text Available ... Get Addicted to Drugs? Does Addiction Run in Families? Why Is It So Hard to Quit Drugs? ... Drug Use and Other People Drug Use and Families Drug Use and Kids Drug Use and Unborn ...

  2. N-(3,4-dimethoxyphenethyl)-4-(6,7-dimethoxy-3,4-dihydroisoquinolin-2[1H]-yl)-6,7-dimethoxyquinazolin-2-amine (CP-100,356) as a "chemical knock-out equivalent" to assess the impact of efflux transporters on oral drug absorption in the rat.

    Science.gov (United States)

    Kalgutkar, Amit S; Frederick, Kosea S; Chupka, Jonathan; Feng, Bo; Kempshall, Sarah; Mireles, Rochelle J; Fenner, Katherine S; Troutman, Matthew D

    2009-12-01

    The utility of the diaminoquinazoline derivative CP-100,356 as an in vivo probe to selectively assess MDR1/BCRP-mediated drug efflux was examined in the rat. CP-100,356 was devoid of inhibition (IC(50) >50 microM) against major human P450 enzymes including P4503A4. In human MDR1-transfected MDCKII cells, CP-100,356 inhibited acetoxymethyl calcein (calcein-AM) uptake (IC(50) approximately 0.5 +/- 0.07 microM) and digoxin transport (IC(50) approximately 1.2 +/- 0.1 microM). Inhibition of prazosin transport (IC(50) approximately 1.5 +/- 0.3 microM) in human BCRP-transfected MDCKII cells by CP-100,356 confirmed the dual MDR1/BCRP inhibitory properties. CP-100,356 was a weak inhibitor of OATP1B1 (IC(50) approximately 66 +/- 1.1 microM) and was devoid of MRP2 inhibition (IC(50) >15 microM). In vivo inhibitory effects of CP-100,356 in rats were examined after coadministration with MDR1 substrate fexofenadine and dual MDR1/BCRP substrate prazosin. Coadministration with increasing doses of CP-100,356 resulted in dramatic increases in systemic exposure of fexofenadine (36- and 80-fold increase in C(max) and AUC at a CP-100,356 dose of 24 mg/kg). Significant differences in prazosin pharmacokinetics were also discernible in CP-100,356-pretreated rats as reflected from a 2.6-fold increase in AUC. Coadministration of CP-100,356 and P4503A substrate midazolam did not result in elevations in systemic exposure of midazolam in the rat. The in vivo methodology should have utility in drug discovery in selective and facile assessment of the role of MDR1 and BCRP efflux transporters in oral absorption of new drug candidates. 2009 Wiley-Liss, Inc. and the American Pharmacists Association

  3. The effect of stress on absorption of acetaminophen.

    Science.gov (United States)

    Flaten, Magne Arve; Asli, Ole; Simonsen, Terje

    2006-05-01

    There is a large variability in the response to pharmacological treatment. Some studies have linked this variability to stress levels, i.e., stress may slow and/or reduce absorption of drugs. The present experiment investigated the hypothesis that stress slows absorption of drugs. Twenty-four volunteers participated in a within-subjects design with three conditions, each lasting 70 min. Subjects watched a movie hypothesized to induce stress, subjects listened to music hypothesized to reduce stress, and in a control condition no stimuli were presented. Each condition was spaced 2 days or more apart. In each condition, subjects received 500 mg oral acetaminophen. Measures of stress and acetaminophen levels were obtained every 10 min. Indices of subjective stress and arousal and cortisol, were increased during the movie compared to control. Subjective arousal and cortisol were decreased during music compared to control. However, acetaminophen levels were the same across time in all three experimental conditions. There was no effect of the experimental manipulations on acetaminophen absorption, indicating that stress was not related to drug absorption. However, stress could play a role in other processes related to drug pharmacokinetics.

  4. Pharmacokinetic aspects of the anti-epileptic drug substance vigabatrin

    DEFF Research Database (Denmark)

    Nøhr, Martha Kampp; Frølund, Sidsel; Holm, René

    2014-01-01

    are discussed in detail. Special focus is on the contribution of the proton-coupled amino acid transporter 1 (PAT1) for intestinal vigabatrin absorption. Furthermore, the review gives an overview of the pharmacokinetic parameters of vigabatrin across different species and drug-food and drug-drug interactions......Drug transporters in various tissues, such as intestine, kidney, liver and brain, are recognized as important mediators of absorption, distribution, metabolism and excretion of drug substances. This review gives a current status on the transporter(s) mediating the absorption, distribution......, metabolism and excretion properties of the anti-epileptic drug substance vigabatrin. For orally administered drugs, like vigabatrin, the absorption from the intestine is a prerequisite for the bioavailability. Therefore, transporter(s) involved in the intestinal absorption of vigabatrin in vitro and in vivo...

  5. Coprecipitation Technique for Preconcentration of Some Metal Ions prior to Graphite Furnace Atomic Absorption Spectrometric Determination

    OpenAIRE

    上田, 穣一

    1998-01-01

    Summary-for the preconcentration of trace ions in the graphite furnace atomic absorption spectrometric determination (GFAAS), a rapid and simple coprecipitation method which does not need the filtration

  6. DETERMINATION OF TOTAL MERCURY IN FISH TISSUES USING PYROLYSIS ATOMIC ABSORPTION SPECTROMETRY WITH GOLD AMALGAMATION

    Science.gov (United States)

    A simple and rapid procedure for measuring total mercury in fish tissues is evaluated and compared with conventional techniques. Using an automated instrument incorporating combustion, preconcentration by amalgamation with gold, and atomic absorption spectrometry (AAS), mill...

  7. Ocular Insert: Dosage Form for Sustain Opthalmic Drug Delivery

    Directory of Open Access Journals (Sweden)

    Sunil Kumar

    2012-06-01

    Full Text Available Except for skin, the eye is the most easily accessible site for topical administration of a medication. Traditional topical ophthalmic formulations (eye drops and ointments have poor bioavailability because of rapid pre-corneal elimination, conjunctival absorption, solution drainage by gravity, induced lacrimation and normal tear turnover. This leads to frequent installations of concentrated medication to achieve a therapeutic effect. The typical “pulse-entry” type drug release observed with ocular aqueous solutions (eye drops, suspensions and ointments can be replaced by more controlled, sustained, and continuous drug delivery, using a controlled-release ocular drug delivery system. Ocular inserts are solid or semisolid sterile preparations, of appropriate size and shape, designed to be inserted behind the eyelid or held on the eye and to deliver drugs for topical or systemic effect. These are polymeric systems into which the drug is incorporated as a solution or dispersion. They are better tolerated as to drainage and tear flow compared with other ophthalmic formulation and produce reliable drug release in the conjunctival cul-de-sac.

  8. PBPK modeling and simulation in drug research and development.

    Science.gov (United States)

    Zhuang, Xiaomei; Lu, Chuang

    2016-09-01

    Physiologically based pharmacokinetic (PBPK) modeling and simulation can be used to predict the pharmacokinetic behavior of drugs in humans using preclinical data. It can also explore the effects of various physiologic parameters such as age, ethnicity, or disease status on human pharmacokinetics, as well as guide dose and dose regiment selection and aid drug-drug interaction risk assessment. PBPK modeling has developed rapidly in the last decade within both the field of academia and the pharmaceutical industry, and has become an integral tool in drug discovery and development. In this mini-review, the concept and methodology of PBPK modeling are briefly introduced. Several case studies were discussed on how PBPK modeling and simulation can be utilized through various stages of drug discovery and development. These case studies are from our own work and the literature for better understanding of the absorption, distribution, metabolism and excretion (ADME) of a drug candidate, and the applications to increase efficiency, reduce the need for animal studies, and perhaps to replace clinical trials. The regulatory acceptance and industrial practices around PBPK modeling and simulation is also discussed.

  9. Phytases for improved iron absorption

    DEFF Research Database (Denmark)

    Nielsen, Anne Veller Friis; Meyer, Anne S.

    2016-01-01

    Phytase enzymes present an alternative to iron supplements, because they have been shown to improve iron absorption by means of catalysing the degradation of a potent iron absorption inhibitor: phytic acid. Phytic acid is a hexaphosphate of inositol and is particularly prevalent in cereal grains...

  10. Wave energy absorption by ducks

    DEFF Research Database (Denmark)

    Kurniawan, Adi

    2017-01-01

    We study the absorption of wave energy by a single and multiple cam-shaped bodies referred to as ducks. Numerical models are developed under the assumptions of linear theory. We consider wave absorption by a single duck as well as by two lines of ducks meeting at an angle....

  11. Water absorption in brick masonry

    NARCIS (Netherlands)

    Brocken, H.J.P.; Smolders, H.R.

    1996-01-01

    The water absorption in brick, mortar that was cured separately, and masonry samples was studied using NMR. Models of the moisture transport are usually formulated on the basis of a diffusion equation. In the case of water absorption in separate brick and mortar samples, the moisture diffusivity in

  12. Simultaneous Determination of Ofloxacin and Flavoxate Hydrochloride by Absorption Ratio and Second Derivative UV Spectrophotometry.

    Science.gov (United States)

    Attimarad, Mahesh

    2010-12-01

    The objective of this study was to develop simple, precise, accurate and sensitive UV spectrophotometric methods for the simultaneous determination of ofloxacin (OFX) and flavoxate HCl (FLX) in pharmaceutical formulations. The first method is based on absorption ratio method, by formation of Q absorbance equation at 289 nm (λmax of OFX) and 322.4 nm (isoabsorptive point). The linearity range was found to be 1 to 30 μg/ml for FLX and OFX. In the method-II second derivative absorption at 311.4 nm for OFX (zero crossing for FLX) and at 246.2 nm for FLX (zero crossing for OFX) was used for the determination of the drugs and the linearity range was found to be 2 to 30 μg/ml for OFX and 2-75 μg /ml for FLX. The accuracy and precision of the methods were determined and validated statistically. Both the methods showed good reproducibility and recovery with % RSD less than 1.5%. Both the methods were found to be rapid, specific, precise and accurate and can be successfully applied for the routine analysis of OFX and FLX in combined dosage form.

  13. Absorption reconstruction improves biodistribution assessment of fluorescent nanoprobes using hybrid Fluorescence-mediated tomography

    NARCIS (Netherlands)

    Gremse, F.; Theek, B.; Kunjachan, S.; Lederle, W.; Pardo, A.; Barth, S.; Lammers, Twan Gerardus Gertudis Maria; Naumann, U.; Kiessling, F.

    2014-01-01

    Aim: Fluorescence-mediated tomography (FMT) holds potential for accelerating diagnostic and theranostic drug development. However, for proper quantitative fluorescence reconstruction, knowledge on optical scattering and absorption, which are highly heterogeneous in different (mouse) tissues, is

  14. Assessment of absorption of four lignan constituents of JingNing ...

    African Journals Online (AJOL)

    Purpose: To study small intestinal absorption of schisadrol A, schisandrol B, schizandrin A and schisandrin B in JingNing particles using in situ single-pass intestinal perfusion (SPIP). Methods: Absorption rate constant (Ka) and apparent permeability (Papp) of the drugs at different concentrations in various parts of rat small ...

  15. Transperitoneal absorption of glucose and amino acids for nutritional support.

    Science.gov (United States)

    Stabile, B E; Borzatta, M

    1987-03-01

    To evaluate the peritoneal membrane as an absorptive surface for nutritional support, 14 New Zealand rabbits with peritoneal catheters were rapidly infused with 75 mL/kg of a 5% glucose and 2.5% mixed amino acid solution. Plasma and peritoneal fluid glucose, amino acid, and electrolyte concentrations and osmolarities were measured serially for six hours following infusion, and nutrient absorptions were calculated. Plasma osmolarity rose minimally, peritoneal fluid osmolarity declined rapidly, and there was a small increase in peritoneal fluid volume. Peritoneal fluid concentrations of glucose and amino acids fell precipitously during the initial two hours, while plasma concentrations rose in reciprocal fashion. Two thirds of the glucose and 83% of the amino acid loads were absorbed at six hours, with most of the absorption occurring within the first two hours. Amino acid absorption was independent of molecular weight and configuration. While glucose and amino acids were rapidly absorbed in adequate amounts, an intraperitoneal nutrition support system will require fat to provide total energy needs.

  16. Drug-mineral interactions

    Energy Technology Data Exchange (ETDEWEB)

    Kramer, L.

    1986-03-01

    The effect of drugs such as glucocorticoids and thyroid extract on calcium metabolism is unknown. However, several other medications affect the excretion and intestinal absorption of calcium. A controlled study was carried out to investigate these aspects. Urinary calcium was determined for 3 months during the long-term intake of the antituberculous drug isoniazid (INH) and of the antibiotic tetracycline. The effect of the diuretics furosemide and hydrochlorothiazide, of several aluminum-containing antacids, of thyroid extract and of corticosteroids was also studied. Metabolic balances of calcium, phosphorus, magnesium and zinc were determined, as well as the intestinal absorption of calcium using Ca 47. Plasma levels, urinary and fecal excretions of Ca 47 were determined. All drugs tested increased urinary calcium except for the diuretic hydrochlorothiazide. Regarding the effect of corticosteroids: the intestinal absorption of calcium was unchanged after the short-term use and was very high after long-term use. The studies have shown that several commonly used drugs induce an increase in urinary calcium excretion which may contribute to calcium loss, if this increase persists for prolonged periods of time. Urinary excretions of phosphorus, magnesium and zinc increased in some of the studies.

  17. Drug Facts

    Medline Plus

    Full Text Available ... Treatment and Recovery Resources? Prevent Drug Use Help Children and Teens Stay Drug-Free Talking to Kids About Drugs: What to Say if You ... drug abuse, addiction, and treatment. Watch Videos Information About Drugs ...

  18. Drug Allergy

    Science.gov (United States)

    ... Loss of consciousness Other conditions resulting from drug allergy Less common drug allergy reactions occur days or ... you take the drug. Drugs commonly linked to allergies Although any drug can cause an allergic reaction, ...

  19. The expected time until absorption when absorption is not certain

    OpenAIRE

    Walker, D. M.

    1998-01-01

    This paper considers continuous-time Markov chains whose state space consists of an irreducible class, , and an absorbing state which is accessible from . The purpose is to provide a way to determine the expected time to absorption conditional on such time being finite, in the case where absorption occurs with probability less than 1. The results are illustrated by applications to the general birth and death process and the linear birth, death and catastrophe process.

  20. Absorption enhancement, mechanistic and toxicity studies of medium chain fatty acids, cyclodextrins and bile salts as peroral absorption enhancers.

    Science.gov (United States)

    Sharma, Pradeep; Varma, Manthena V S; Chawla, Harmander P S; Panchagnula, Ramesh

    2005-01-01

    The objective of the present investigation was to evaluate an oral 'drug delivery' approach, which involves co-administration of absorption enhancers (AEs). The representative low permeable hydrophilic (biopharmaceutic classification system (BCS) Class III) drugs used in the study comprised of cefotaxime sodium and ceftazidime pentahydrate, whereas low permeable lipophilic (BCS Class IV) drugs include cyclosporin A and lovastatin. AEs from three different chemical classes, namely, medium chain fatty acids (sodium caprylate and caprate), cyclodextrins (beta-cyclodextrin, hydroxypropyl beta-cyclodextrin) and bile salts (sodium cholate and deoxycholate) were evaluated for absorption enhancement efficacy, mechanism of action and toxicity using in vitro everted intestinal sac model. These AEs were found to enhance intestinal permeability of drugs from 2- to 27-fold. Light microscopy studies of intestinal sac incubated with AEs for 120 min revealed morphological changes in absorptive mucosa and rank order of toxicity were cyclodextrins>bile salts congruent with medium chain fatty acids. Fluorescence polarization studies indicated that brush bordered membrane vesicles labeled with lipophilic (DPH, 12AS) and hydrophilic dyes (ANS), when treated with AEs exhibited concentration and time dependent decrease in fluorescence polarization. Total protein released in presence of AEs was more than control but considerably less than EDTA (0.58% w/v), which is known to cause toxic release of proteins from cell. Overall, AEs were found to significantly enhance drug permeability by decreasing lipid membrane fluidity and/or interacting with hydrophilic domains of membrane, and has the potential to improve oral delivery.

  1. Intestinal alkaline phosphatase: selective endocytosis from the enterocyte brush border during fat absorption

    DEFF Research Database (Denmark)

    Hansen, Gert Helge; Niels-Christiansen, Lise-Lotte; Immerdal, Lissi

    2007-01-01

    explants. By immunofluorescence microscopy, fat absorption caused a translocation of IAP from the enterocyte brush border to the interior of the cell, whereas other brush-border enzymes were unaffected. By electron microscopy, the translocation occurred by a rapid (5 min) induction of endocytosis via....... A lipid analysis revealed that fat absorption caused a marked increase in the microvillar membrane contents of free fatty acids. In conclusion, fat absorption rapidly induces a transient clathrin-dependent endocytosis via coated pits from the enterocyte brush border. The process selectively internalizes...

  2. Reproducibility of The Random Incidence Absorption Coefficient Converted From the Sabine Absorption Coefficient

    DEFF Research Database (Denmark)

    Jeong, Cheol-Ho; Chang, Ji-ho

    2015-01-01

    Absorption coefficients measured in reverberation chambers, Sabine absorption coefficients, suffer from two major problems. Firstly, they sometimes exceed unity. Secondly, the reproducibility of the Sabine absorption coefficients is quite poor, meaning that the Sabine absorption coefficients vary...

  3. Progress in Drug Delivery to the Central Nervous System by the Prodrug Approach

    Directory of Open Access Journals (Sweden)

    Silvia Vertuani

    2008-05-01

    Full Text Available This review describes specific strategies for targeting to the central nervoussystem (CNS. Systemically administered drugs can reach the brain by crossing one of twophysiological barriers resistant to free diffusion of most molecules from blood to CNS: theendothelial blood-brain barrier or the epithelial blood-cerebrospinal fluid barrier. Thesetissues constitute both transport and enzymatic barriers. The most common strategy fordesigning effective prodrugs relies on the increase of parent drug lipophilicity. However,increasing lipophilicity without a concomitant increase in rate and selectivity of prodrugbioconversion in the brain will result in failure. In these regards, consideration of theenzymes present in brain tissue and in the barriers is essential for a successful approach.Nasal administration of lipophilic prodrugs can be a promising alternative non-invasiveroute to improve brain targeting of the parent drugs due to fast absorption and rapid onsetof drug action. The carrier-mediated absorption of drugs and prodrugs across epithelial andendothelial barriers is emerging as another novel trend in biotherapeutics. Several specifictransporters have been identified in boundary tissues between blood and CNScompartments. Some of them are involved in the active supply of nutrients and have been used to explore prodrug approaches with improved brain delivery. The feasibility of CNSuptake of appropriately designed prodrugs via these transporters is described in detail.

  4. Structure-based in silico model profiles the binding constant of poorly soluble drugs with β-cyclodextrin.

    Science.gov (United States)

    Li, Haiyan; Sun, Jin; Wang, Yongjun; Sui, Xiaofan; Sun, Le; Zhang, Jiwen; He, Zhonggui

    2011-01-18

    Cyclodextrin inclusion complexation technique is the key method to enhance the solubility and absorption of poorly soluble drugs in the early development stage, and thus it is essential to predict the binding constant between drug molecules and cyclodextrin. Structure-based in silico model was constructed for a data set of 86 poorly soluble drugs and used to profile the binding constant of drug-β-cyclodextrin inclusion complex. The stepwise regression was employed to select the optimum subset of the independent variables. The in silico model was built by the multiple linear regression method and validated by the residual analysis, the normal Probability-Probability plot and Williams plot. For the entire data set, the R(2) and Q(2) of the model were 0.78 and 0.67, respectively. The results indicated that the fitted model is robust, stable and satisfies all the prerequisites of the regression models. The chemical space position and important contributors were compared between selected drug molecules and organic compounds available in the literature. It was suggested that the binding behavior of drug molecules with β-CD should differ from that of the common organic compounds. Focusing on structurally diverse drugs, the in silico model can be used as an efficient tool to rapidly screen the drug-β-cyclodextrin inclusion complex stability and to rationally design the new drug delivery system of poorly soluble drugs. Copyright © 2010 Elsevier B.V. All rights reserved.

  5. Accidental death via intravaginal absorption of methamphetamine.

    Science.gov (United States)

    Jones, Prentiss; Mutsvunguma, Romeo; Prahlow, Joseph A

    2014-06-01

    In this paper a drug fatality that involved an unintended drug delivery route is described. The decedent, a 23-year-old female in custody in a county jail on suspicion of a felony drug offense, was discovered in a holding cell unconscious and unresponsive. Following unsuccessful cardiopulmonary resuscitation attempts she was pronounced dead at the scene. At autopsy a wad of multiple small loosely wrapped plastic packages held together with another layer of clear plastic was found in the decedent's vagina. The smaller plastic packages contained an off-white pasty substance that was later identified as methamphetamine. Toxicological testing of specimens collected during autopsy revealed methamphetamine in the decedent's subclavian blood, vitreous fluid, and urine at extremely high concentrations (42.6, 20.1, and 771 mg/L, respectively). Amphetamine, the active metabolite of methamphetamine, was also present in the subclavian blood, vitreous fluid, and urine at significant concentrations (1.3, 0.5, and 20.4 mg/L, respectively). The cause of death was attributed to toxic effects of methamphetamine and the manner of death was ruled accidental. This report suggests that lethal concentrations of methamphetamine may be distributed to the systemic circulation via intravaginal absorption.

  6. Drug Facts

    Medline Plus

    Full Text Available ... signs and symptoms of someone with a drug use problem? How Does Drug Use Become an Addiction? What Makes Someone More Likely ... Hard to Quit Drugs? Effects of Drugs Drug Use and Other People Drug Use and Families Drug ...

  7. Drug Facts

    Medline Plus

    Full Text Available ... Why Is It So Hard to Quit Drugs? Effects of Drugs Drug Use and Other People Drug Use and ... Unborn Children Drug Use and Your Health Other Effects on the Body Drug Use Hurts Brains Drug Use and Mental Health ...

  8. Improving pharmacokinetic-pharmacodynamic modeling to investigate anti-infective chemotherapy with application to the current generation of antimalarial drugs.

    Directory of Open Access Journals (Sweden)

    Katherine Kay

    Full Text Available Mechanism-based pharmacokinetic-pharmacodynamic (PK/PD modelling is the standard computational technique for simulating drug treatment of infectious diseases with the potential to enhance our understanding of drug treatment outcomes, drug deployment strategies, and dosing regimens. Standard methodologies assume only a single drug is used, it acts only in its unconverted form, and that oral drugs are instantaneously absorbed across the gut wall to their site of action. For drugs with short half-lives, this absorption period accounts for a significant period of their time in the body. Treatment of infectious diseases often uses combination therapies, so we refined and substantially extended the PK/PD methodologies to incorporate (i time lags and drug concentration profiles resulting from absorption across the gut wall and, if required, conversion to another active form; (ii multiple drugs within a treatment combination; (iii differing modes of action of drugs in the combination: additive, synergistic, antagonistic; (iv drugs converted to an active metabolite with a similar mode of action. This methodology was applied to a case study of two first-line malaria treatments based on artemisinin combination therapies (ACTs, artemether-lumefantrine and artesunate-mefloquine where the likelihood of increased artemisinin tolerance/resistance has led to speculation on their continued long-term effectiveness. We note previous estimates of artemisinin kill rate were underestimated by a factor of seven, both the unconverted and converted form of the artemisinins kill parasites and the extended PK/PD methodology produced results consistent with field observations. The simulations predict that a potentially rapid decline in ACT effectiveness is likely to occur as artemisinin resistance spreads, emphasising the importance of containing the spread of artemisinin resistance before it results in widespread drug failure. We found that PK/PD data is generally very

  9. [Pharmacotherapy of hyperthyreosis--adverse drug reactions].

    Science.gov (United States)

    Perger, Ludwig; Bürgi, Ulrich; Fattinger, Karin

    2011-06-01

    The antithyroid drugs mainly include thioimidazole (carbimazole, methimazole=thiamazole) and propylthiouracil. After absorption, carbimazole is rapidly metabolized to methimazole and thus switching between these two drugs should not be considered in case of side effects. Furthermore, in case of side effects, sometimes even cross reactions between thioimidazoles and propylthiouracil occur. Common and typical adverse reactions of antithyroid drugs include dose dependent hypothyroidism and thus thyroid function should be repeatedly checked while the patient is on antithyroid drugs. Furthermore, pruritus and rash may develop. In this case, one might try to switch from thioimidazoles to propylthiouracil or vice versa. Antithyroid drugs may cause mild dose dependent neutropenia or severe allergy-mediated agranulocytosis, which typically occurs during the first three months of treatment, has an incidence of 3 per 10,000 patients and cross reactivity between thioimidazoles to propylthiouracil may occur. Rarely, antithyroid drugs can cause aplastic anemia. Mainly propylthiouracil, but sometimes also methimazole may lead to an asymptomatic transient increase in liver enzymes or to severe, even lethal liver injury of cholestatic or hepatocellular pattern. Since propylthiouracil associated liver injury was observed increasingly among children and adolescent, it has been suggested to prefer thioimidazoles for these patients. Because of these potential serious adverse effects, physicians should advise patients to immediately seek medical help if they get a fever or sore throat or malaise, abdominal complaints or jaundice, respectively. Furthermore, arthralgias may develop in 1-5% of patients under both antithyroid drugs. Since arthralgias may be the first symptom of more serious immunologic side effects, it is recommended to stop the antithyroid drug in this case. Drug induced polyarthritis mainly develops during the first month of therapy, whereas ANCA-positive vasculitis is

  10. Desensitization for drug allergy.

    Science.gov (United States)

    Castells, Mariana

    2006-12-01

    Desensitization for drug allergy is the induction of temporary clinical unresponsiveness to drug antigens. Gradual reintroduction of small doses of drug antigen at fixed time intervals allows for the delivery of full therapeutic doses, protecting patients from anaphylaxis. Rapid desensitizations permit the use of essential antibiotics in severely infected allergic patients or aspirin in aspirin-sensitive cardiac patients undergoing revascularization. We review the indications and outcomes of recent protocols for desensitization to antibiotics and aspirin. Despite the success of rapid desensitizations, the cellular and molecular inhibitory mechanisms are incompletely understood. In-vitro mast cell and basophil models implicate molecular signaling molecules syk and STAT6. Rapid desensitization protocols treat type I mast cell/IgE dependent reactions, such as anaphylaxis, as seen with sensitization to penicillin, cephalosporins, and other antibiotics. Anaphylactoid reactions induced upon initial drug exposure and with similar clinical presentation as immunoglobulin E-mediated reactions, as seen with aspirin, vancomycin and taxenes, can also be treated with rapid desensitizations. Successful rapid desensitization protocols for treating adverse reactions to antibiotics and aspirin allow for treatment of critically infected patients and aspirin-sensitive cardiac patients. Standardized protocols with high success rates should be implemented as the standard of care.

  11. Early pharmaceutical profiling to predict oral drug absorption

    DEFF Research Database (Denmark)

    Bergström, Christel A S; Holm, René; Jørgensen, Søren Astrup

    2014-01-01

    Preformulation measurements are used to estimate the fraction absorbed in vivo for orally administered compounds and thereby allow an early evaluation of the need for enabling formulations. As part of the Oral Biopharmaceutical Tools (OrBiTo) project, this review provides a summary of the pharmac...

  12. Absorption and Metabolism of Xanthophylls

    Directory of Open Access Journals (Sweden)

    Eiichi Kotake-Nara

    2011-06-01

    Full Text Available Dietary carotenoids, especially xanthophylls, have attracted significant attention because of their characteristic biological activities, including anti-allergic, anti-cancer, and anti-obese actions. Although no less than forty carotenoids are ingested under usual dietary habits, only six carotenoids and their metabolites have been found in human tissues, suggesting selectivity in the intestinal absorption of carotenoids. Recently, facilitated diffusion in addition to simple diffusion has been reported to mediate the intestinal absorption of carotenoids in mammals. The selective absorption of carotenoids may be caused by uptake to the intestinal epithelia by the facilitated diffusion and an unknown excretion to intestinal lumen. It is well known that β-carotene can be metabolized to vitamin A after intestinal absorption of carotenoids, but little is known about the metabolic transformation of non provitamin A xanthophylls. The enzymatic oxidation of the secondary hydroxyl group leading to keto-carotenoids would occur as a common pathway of xanthophyll metabolism in mammals. This paper reviews the absorption and metabolism of xanthophylls by introducing recent advances in this field.

  13. Drug Facts

    Medline Plus

    Full Text Available ... Drug Use and Kids Drug Use and Unborn Children Drug Use and Your Health Other Effects on ... Someone Find Treatment and Recovery Resources? Prevention Help Children and Teens Stay Drug-Free Talking to Kids ...

  14. Drug Facts

    Medline Plus

    Full Text Available ... and symptoms of someone with a drug use problem? How Does Drug Use Become an Addiction? What ... Use Hurts Brains Drug Use and Mental Health Problems Often Happen Together The Link Between Drug Use ...

  15. Drug Facts

    Medline Plus

    Full Text Available ... Drug Use and Your Health Other Effects on the Body Drug Use Hurts Brains Drug Use and Mental Health Problems Often Happen Together The Link Between Drug Use and HIV/AIDS Treatment & ...

  16. Drug Facts

    Medline Plus

    Full Text Available ... Body Drug Use Hurts Brains Drug Use and Mental Health Problems Often Happen Together The Link Between Drug Use and HIV/AIDS Treatment & Recovery Why Does a Person Need Treatment? Does Drug ...

  17. Drug Safety

    Science.gov (United States)

    ... over-the-counter drug. The FDA evaluates the safety of a drug by looking at Side effects ... clinical trials The FDA also monitors a drug's safety after approval. For you, drug safety means buying ...

  18. Drug Abuse

    Science.gov (United States)

    ... or injuries among Americans. Abused drugs include Methamphetamine Anabolic steroids Club drugs Cocaine Heroin Inhalants Marijuana Prescription drugs, including opioids Drug abuse also plays a role in many major social ...

  19. Drug Facts

    Medline Plus

    Full Text Available ... Use and Unborn Children Drug Use and Your Health Other Effects on the Body Drug Use Hurts Brains Drug Use and Mental Health Problems Often Happen Together The Link Between Drug ...

  20. Drug Facts

    Medline Plus

    Full Text Available ... Where Can Someone Find Treatment and Recovery Resources? Prevent Drug Use Help Children and Teens Stay Drug- ... You Used Drugs in the Past Drug Use Prevention Phone Numbers and Websites Search Share Listen English ...

  1. The Hyperspectral Absorption Sensor - Advantages and challenges of continuous, in situ absorption coefficient measurements

    Science.gov (United States)

    Wollschläger, J.; Röttgers, R.; Petersen, W.; Zielinski, O.

    2016-12-01

    The marine environment is a highly dynamic system and rapid changes can occur on both spatial and temporal scales. This is especially true for the phytoplankton, which forms the basis of the marine food web. Comprehensive monitoring and investigation of its often patchy distribution and seasonal succession requires sensors which are fast, can be used in situ, and are automatable to reduce operational costs. Optical sensors fulfil all of these requirements. Due to its variety of (sometimes group-specific) photosynthetic and photoprotective pigments, phytoplankton has a considerable influence on the water's inherent and apparent optical properties. This offers the possibility to obtain information about the phytoplankton present by measuring these properties, for example the absorption coefficients of the water at the photosynthetic active wavelengths. However, common obstacles for obtaining high quality absorption coefficient measurements are the often low concentration of absorbing material present as well as errors introduced by light scattering on particles. These problems can be overcome by instruments taking advantage of integrating cavities, like the point-source integrating cavity absorption meter (PSICAM). The Hyperspectral Absorption Sensor (HyAbS) is the result of an attempt to combine the advantages of the PSICAM approach with the high resolution of continuous measurements. Its setup and working principle is described, and challenges and potential solutions with respect to its long-term automated operation are highlighted. This includes the replacement of the dye-based calibration of the instrument by a solid standard calibration. Finally, also results from field test with respect to phytoplankton investigation are given.

  2. Lunar absorption spectrophotometer for measuring atmospheric water vapor.

    Science.gov (United States)

    Querel, Richard R; Naylor, David A

    2011-02-01

    A novel instrument has been designed to measure the nighttime atmospheric water vapor column abundance by near-infrared absorption spectrophotometry of the Moon. The instrument provides a simple, effective, portable, and inexpensive means of rapidly measuring the water vapor content along the lunar line of sight. Moreover, the instrument is relatively insensitive to the atmospheric model used and, thus, serves to provide an independent calibration for other measures of precipitable water vapor from both ground- and space-based platforms.

  3. Cytochromes P450 and drug resistance

    NARCIS (Netherlands)

    Doehmer, J.; Goeptar, A R; Vermeulen, N P

    1993-01-01

    Cytochromes P450 are the key enzymes for activating and inactivating many drugs, in particular anticancer drugs. Therefore, individual expression levels of cytochromes P450 may play a crucial role in drug safety and drug efficacy. Overexpression of cytochrome P450 may yield rapid turnover and

  4. Rapidly Developing Toxic Epidermal Necrolysis

    Directory of Open Access Journals (Sweden)

    Viktoria Oline Barrios Poulsen

    2013-01-01

    Full Text Available Severe cutaneous reactions with potentially fatal outcomes can have many different causes. The Stevens-Johnson syndrome (SJS and toxic epidermal necrolysis (TEN are rare. They are characterized by a low incidence but high mortality, and drugs are most commonly implicated. Urgent active therapy is required. Prompt recognition and withdrawal of suspect drug and rapid intervention can result in favourable outcome. No further international guidelines for treatment exist, and much of the treatment relies on old or experimental concepts with no scientific evidence. We report on a 54-year-old man experiencing rapidly developing drug-induced severe TEN and presented multiorgan failure involving the respiratory and circulatory system, coagulopathy, and renal insufficiency. Detachment counted 30% of total body surface area (TBSA. SCORTEN = 5, indicating a mortality rate >90%. The patient was sedated and mechanically ventilated, supported with fluids and inotropes to maintain a stable circulation. Component therapy was guided by thromboelastography (TEG. The patient received plasmapheresis, and shock reversal treatment was initiated. He was transferred to a specialized intensive care burn unit within 24 hours from admittance. The initial care was continued, and hemodialysis was started. Pulmonary, circulatory, and renal sequelae resolved with intensive care, and re-epithelialization progressed slowly. The patient was discharged home on hospital day 19.

  5. Enhanced absorption cycle computer model

    Science.gov (United States)

    Grossman, G.; Wilk, M.

    1993-09-01

    Absorption heat pumps have received renewed and increasing attention in the past two decades. The rising cost of electricity has made the particular features of this heat-powered cycle attractive for both residential and industrial applications. Solar-powered absorption chillers, gas-fired domestic heat pumps, and waste-heat-powered industrial temperature boosters are a few of the applications recently subjected to intensive research and development. The absorption heat pump research community has begun to search for both advanced cycles in various multistage configurations and new working fluid combinations with potential for enhanced performance and reliability. The development of working absorption systems has created a need for reliable and effective system simulations. A computer code has been developed for simulation of absorption systems at steady state in a flexible and modular form, making it possible to investigate various cycle configurations with different working fluids. The code is based on unit subroutines containing the governing equations for the system's components and property subroutines containing thermodynamic properties of the working fluids. The user conveys to the computer an image of his cycle by specifying the different subunits and their interconnections. Based on this information, the program calculates the temperature, flow rate, concentration, pressure, and vapor fraction at each state point in the system, and the heat duty at each unit, from which the coefficient of performance (COP) may be determined. This report describes the code and its operation, including improvements introduced into the present version. Simulation results are described for LiBr-H2O triple-effect cycles, LiCl-H2O solar-powered open absorption cycles, and NH3-H2O single-effect and generator-absorber heat exchange cycles. An appendix contains the user's manual.

  6. Absorption Efficiency of Receiving Antennas

    DEFF Research Database (Denmark)

    Andersen, Jørgen Bach; Frandsen, Aksel

    2005-01-01

    A receiving antenna with a matched load will always scatter some power. This paper sets an upper and a lower bound on the absorption efficiency (absorbed power over sum of absorbed and scattered powers), which lies between 0 and 100% depending on the directivities of the antenna and scatter...... patterns. It can approach 100% as closely as desired, although in practice this may not be an attractive solution. An example with a small endfire array of dipoles shows an efficiency of 93%. Several examples of small conical horn antennas are also given, and they all have absorption efficiencies less than...

  7. Nonlinear absorption in discrete systems

    Energy Technology Data Exchange (ETDEWEB)

    Spire, A; Leon, J [Physique Mathematique et Theorique, CNRS-UMR5825, Universite Montpellier 2, 34095 Montpellier (France)

    2004-10-01

    In the context of nonlinear scattering, a continuous wave incident onto a nonlinear discrete molecular chain of coupled oscillators can be partially absorbed as a result of a three-wave resonant interaction that couples two HF-waves of frequencies close to the edge of the Brillouin zone. Hence both nonlinearity and discreteness are necessary for generating this new absorption process which manifests itself by soliton generation in the medium. As a paradigm of this nonlinear absorption we consider here the Davydov model that describes exciton-phonon coupling in hydrogen-bonded molecular chains.

  8. Absorption-heat-pump system

    Science.gov (United States)

    Grossman, G.; Perez-Blanco, H.

    1983-06-16

    An improvement in an absorption heat pump cycle is obtained by adding adiabatic absorption and desorption steps to the absorber and desorber of the system. The adiabatic processes make it possible to obtain the highest temperature in the absorber before any heat is removed from it and the lowest temperature in the desorber before heat is added to it, allowing for efficient utilization of the thermodynamic availability of the heat supply stream. The improved system can operate with a larger difference between high and low working fluid concentrations, less circulation losses, and more efficient heat exchange than a conventional system.

  9. The mucoadhesive and gastroretentive properties of hydrophobin-coated porous silicon nanoparticle oral drug delivery systems.

    Science.gov (United States)

    Sarparanta, Mirkka P; Bimbo, Luis M; Mäkilä, Ermei M; Salonen, Jarno J; Laaksonen, Päivi H; Helariutta, A M Kerttuli; Linder, Markus B; Hirvonen, Jouni T; Laaksonen, Timo J; Santos, Hélder A; Airaksinen, Anu J

    2012-04-01

    Impediments to intestinal absorption, such as poor solubility and instability in the variable conditions of the gastrointestinal (GI) tract plague many of the current drugs restricting their oral bioavailability. Particulate drug delivery systems hold great promise in solving these problems, but their effectiveness might be limited by their often rapid transit through the GI tract. Here we describe a bioadhesive oral drug delivery system based on thermally-hydrocarbonized porous silicon (THCPSi) functionalized with a self-assembled amphiphilic protein coating consisting of a class II hydrophobin (HFBII) from Trichoderma reesei. The HFBII-THCPSi nanoparticles were found to be non-cytotoxic and mucoadhesive in AGS cells, prompting their use in a biodistribution study in rats after oral administration. The passage of HFBII-THCPSi nanoparticles in the rat GI tract was significantly slower than that of uncoated THCPSi, and the nanoparticles were retained in stomach by gastric mucoadhesion up to 3 h after administration. Upon entry to the small intestine, the mucoadhesive properties were lost, resulting in the rapid transit of the nanoparticles through the remainder of the GI tract. The gastroretentive drug delivery system with a dual function presented here is a viable alternative for improving drug bioavailability in the oral route. Copyright © 2012 Elsevier Ltd. All rights reserved.

  10. Drug: D05304 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D05304 Drug White petrolatum (JP16); Petrolatum, white (USP); Moroline (TN) Pharmac...es 7121 Oil bases D05304 White petrolatum (JP16); Petrolatum, white (USP) CAS: 8009-03-8 PubChem: 17398273 ... ...ment [DR:D05239], Absorptive ointment [DR:D05354], Duratears ointment (TN), Lacri-Lube NP (TN), Refresh PM (TN), Hydrophilic petrolat...um [DR:D05332], Vusion (TN) Therapeutic category of drug

  11. Drug: D01665 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D01665 Drug Voglibose (JP16/USAN/INN); Basen (TN) C10H21NO7 267.1318 267.2762 D01665.gif Antidiabeti...se metabolism hsa04973(8972) Carbohydrate digestion and absorption map07051 Antidiabetics Therapeutic catego...ry of drugs in Japan [BR:br08301] 3 Agents affecting metabolism 39 Other agents affecting metabolism 396 Antidiabeti

  12. Drug trafficking: recent advances in therapeutics and disease.

    Science.gov (United States)

    Sprowl, J A; Sparreboom, A

    2012-11-01

    Drug transporter proteins are of ever-increasing interest because of their role both in processes regulating pharmacokinetic properties of drugs (absorption, distribution, and elimination) and in the development of cellular drug resistance through decreased uptake or increased efflux of drugs in the target organ or tumor. Further understanding of the role of transporters in drug-drug interactions and identification of these proteins as possible therapeutic targets could contribute to improved treatment of a wide variety of diseases.

  13. Aerosol Absorption Measurements in MILAGRO.

    Science.gov (United States)

    Gaffney, J. S.; Marley, N. A.; Arnott, W. P.; Paredes-Miranda, L.; Barnard, J. C.

    2007-12-01

    During the month of March 2006, a number of instruments were used to determine the absorption characteristics of aerosols found in the Mexico City Megacity and nearby Valley of Mexico. These measurements were taken as part of the Department of Energy's Megacity Aerosol Experiment - Mexico City (MAX-Mex) that was carried out in collaboration with the Megacity Interactions: Local and Global Research Observations (MILAGRO) campaign. MILAGRO was a joint effort between the DOE, NSF, NASA, and Mexican agencies aimed at understanding the impacts of a megacity on the urban and regional scale. A super-site was operated at the Instituto Mexicano de Petroleo in Mexico City (designated T-0) and at the Universidad Technologica de Tecamac (designated T-1) that was located about 35 km to the north east of the T-0 site in the State of Mexico. A third site was located at a private rancho in the State of Hidalgo approximately another 35 km to the northeast (designated T-2). Aerosol absorption measurements were taken in real time using a number of instruments at the T-0 and T-1 sites. These included a seven wavelength aethalometer, a multi-angle absorption photometer (MAAP), and a photo-acoustic spectrometer. Aerosol absorption was also derived from spectral radiometers including a multi-filter rotating band spectral radiometer (MFRSR). The results clearly indicate that there is significant aerosol absorption by the aerosols in the Mexico City megacity region. The absorption can lead to single scattering albedo reduction leading to values below 0.5 under some circumstances. The absorption is also found to deviate from that expected for a "well-behaved" soot anticipated from diesel engine emissions, i.e. from a simple 1/lambda wavelength dependence for absorption. Indeed, enhanced absorption is seen in the region of 300-450 nm in many cases, particularly in the afternoon periods indicating that secondary organic aerosols are contributing to the aerosol absorption. This is likely due

  14. Mechanisms for oral absorption of poorly water-soluble compounds

    DEFF Research Database (Denmark)

    Lind, Marianne Ladegaard

    viability and monolayer integrity were developed. The effect of simulated intestinal fluids on the absorption of the poorly water-soluble drug substances, estradiol and diazepam, was studied. The flux of both drug substances across the Caco-2 cells was decreased when simulated intestinal fluids containing...... micelles were applied in the apical compartment. The flux of diazepam was further decreased when pharmaceutical surfactants (Labrafil, fatty acid ester of polyethylene glycol, Cremophor RH40, polysorbate 80 and Pluronic L81) were added to the medium. This was most likely caused by partial incorporation...... of the drug substances in the micelles, and accordingly the drug substances need to be released from the micelles before being absorbed. However, the solubility of estradiol and diazepam was higher in the simulated intestinal fluids, indicating that the presence of bile salts, phospholipids and lipolysis...

  15. Investigating the correlation between in vivo absorption and in vitro release of fenofibrate from lipid matrix particles in biorelevant medium

    DEFF Research Database (Denmark)

    Borkar, Nrupa Nitin; Xia, Dengning; Holm, René

    2014-01-01

    Lipid matrix particles (LMP) may be used as better carriers for poorly water-soluble drugs than liquid lipid carriers because of reduced drug mobilization in the formulations. However, the digestion process of solid lipid particles and their effect on the absorption of poorly water-soluble drugs...

  16. Drugs, drugs--who has the drugs?

    Science.gov (United States)

    Blair, James

    2012-01-01

    Drug diversion, although on the increase, is not the only problem involving drugs that hospital security officials should be concerned with. Growing drug shortages, offshore production, counterfeiting, and weaknesses in the drug supply chain in case of a world-wide pandemic, are even greater causes for concern, the author claims.

  17. Low-Absorption Laser Windows

    Science.gov (United States)

    1976-04-01

    ABSORPTION MEASUREMENTS AT 1.06 Urn James W. Davisson U.S. Naval Research Laboratory Washington, D.C. 20375 ABSTRACT A procedure for the chemical poli...W. Davisson , Fourth Laser Window Materials Conf. p. 466). The alkaline earth fluorides and LiF were mechanically polished by rubbing: till dry

  18. Theory of graphene saturable absorption

    Science.gov (United States)

    Marini, A.; Cox, J. D.; García de Abajo, F. J.

    2017-03-01

    Saturable absorption is a nonperturbative nonlinear optical phenomenon that plays a pivotal role in the generation of ultrafast light pulses. Here we show that this effect emerges in graphene at unprecedentedly low light intensities, thus opening avenues to new nonlinear physics and applications in optical technology. Specifically, we theoretically investigate saturable absorption in extended graphene by developing a semianalytical nonperturbative single-particle approach, describing electron dynamics in the atomically-thin material using the two-dimensional Dirac equation for massless Dirac fermions, which is recast in the form of generalized Bloch equations. By solving the electron dynamics nonperturbatively, we account for both interband and intraband contributions to the intensity-dependent saturated conductivity and conclude that the former dominates regardless of the intrinsic doping state of the material. We obtain results in qualitative agreement with atomistic quantum-mechanical simulations of graphene nanoribbons including electron-electron interactions, finite-size, and higher-band effects. Remarkably, such effects are found to affect mainly the linear absorption, while the predicted saturation intensities are in good quantitative agreement in the limit of extended graphene. Additionally, we find that the modulation depth of saturable absorption in graphene can be electrically manipulated through an externally applied gate voltage. Our results are relevant for the development of graphene-based optoelectronic devices, as well as for applications in mode-locking and random lasers.

  19. Aerosol absorption and radiative forcing

    Directory of Open Access Journals (Sweden)

    P. Stier

    2007-10-01

    Full Text Available We present a comprehensive examination of aerosol absorption with a focus on evaluating the sensitivity of the global distribution of aerosol absorption to key uncertainties in the process representation. For this purpose we extended the comprehensive aerosol-climate model ECHAM5-HAM by effective medium approximations for the calculation of aerosol effective refractive indices, updated black carbon refractive indices, new cloud radiative properties considering the effect of aerosol inclusions, as well as by modules for the calculation of long-wave aerosol radiative properties and instantaneous aerosol forcing. The evaluation of the simulated aerosol absorption optical depth with the AERONET sun-photometer network shows a good agreement in the large scale global patterns. On a regional basis it becomes evident that the update of the BC refractive indices to Bond and Bergstrom (2006 significantly improves the previous underestimation of the aerosol absorption optical depth. In the global annual-mean, absorption acts to reduce the short-wave anthropogenic aerosol top-of-atmosphere (TOA radiative forcing clear-sky from −0.79 to −0.53 W m−2 (33% and all-sky from −0.47 to −0.13 W m−2 (72%. Our results confirm that basic assumptions about the BC refractive index play a key role for aerosol absorption and radiative forcing. The effect of the usage of more accurate effective medium approximations is comparably small. We demonstrate that the diversity in the AeroCom land-surface albedo fields contributes to the uncertainty in the simulated anthropogenic aerosol radiative forcings: the usage of an upper versus lower bound of the AeroCom land albedos introduces a global annual-mean TOA forcing range of 0.19 W m−2 (36% clear-sky and of 0.12 W m−2 (92% all-sky. The consideration of black carbon inclusions on cloud radiative properties results in a small global annual-mean all-sky absorption of 0.05 W

  20. Absorptive capacity and smart companies

    Directory of Open Access Journals (Sweden)

    Patricia Moro González

    2014-12-01

    Full Text Available Purpose: The current competitive environment is substantially modifying the organizations’ learning processes due to a global increase of available information allowing this to be transformed into knowledge. This opportunity has been exploited since the nineties by the tools of “Business Analytics” and “Business Intelligence” but, nevertheless, being integrated in the study of new organizational capacities engaged in the process of creating intelligence inside organizations is still an outstanding task. The review of the concept of absorptive capacity and a detailed study from the perspective of this new reality will be the main objective of study of this paper.Design/methodology/approach: By comparing classical absorptive capacity and absorptive capacity from the point of view of information management tools in each one of the three stages of the organizational learning cycle, some gaps of the former are overcome/fulfilled. The academic/bibliographical references provided in this paper have been obtained from ISI web of knowledge, Scopus and Dialnet data bases, supporting the state of affairs on absorptive capacity and thereafter filtering by "Business Intelligence" and "Business Analytics". Specialized websites and Business Schools` Publications there have also been included, crowning the content on information management tools used that are currently used in the strategic consulting.Findings: Our contribution to the literature is the development of "smart absorptive capacity". This is a new capacity emerging from the reformulation of the classical concept of absorptive capacity wherein some aspects of its definition that might have been omitted are emphasized. The result of this new approach is the creation of a new Theoretical Model of Organizational Intelligence, which aims to explain, within the framework of the Resources and Capabilities Theory, the competitive advantage achieved by the so-called smart companies

  1. Drug: D10178 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available Protein digestion and absorption Target-based classification of drugs [BR:br08310] Enzymes Hydrolases dipep...of type 2 diabetes [DS:H00409] dipeptidyl-peptidase 4 (DPP4) inhibitor [HSA:1803] [KO:K01278] hsa04974(1803)

  2. Drug: D05354 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available apeutic category: 7122 Therapeutic category of drugs in Japan [BR:br08301] 7 Agents not mainly for therape...utic purpose 71 Dispensing medicines 712 Ointment bases 7122 Emulsion bases D05354 Absorptive ointment (JP16) PubChem: 17398289 ...

  3. Drug: D06553 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available ipeptidyl-peptidase 4 (DPP4) inhibitor [HSA:1803] [KO:K01278] hsa04974(1803) Protein digestion and absorption map07051 Antidiabeti...ents affecting metabolism 39 Other agents affecting metabolism 396 Antidiabetic agents 3969 Others D06553 Al...te (JAN/USAN) USP drug classification [BR:br08302] Blood Glucose Regulators Antidiabetic Agents Alogliptin D

  4. Drug: D00216 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available n hsa04973(279+280+8972) Carbohydrate digestion and absorption map07051 Antidiabetics Therapeutic category o...ting metabolism 396 Antidiabetic agents 3969 Others D00216 Acarbose (JAN/USAN/INN) Anatomical Therapeutic Ch...0BF01 Acarbose D00216 Acarbose (JAN/USAN/INN) USP drug classification [BR:br08302] Blood Glucose Regulators Antidiabeti

  5. Drug: D09566 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available -peptidase 4 (DPP4) inhibitor [HSA:1803] [KO:K01278] hsa04974(1803) Protein digestion and absorption map07051 Antidiabeti...cting metabolism 39 Other agents affecting metabolism 396 Antidiabetic agents 3969 Others D09566 Linagliptin...P drug classification [BR:br08302] Blood Glucose Regulators Antidiabetic Agents Linagliptin D09566 Linaglipt

  6. Drug: D08516 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D08516 Drug Sitagliptin (Prop.INN) C16H15F6N5O 407.1181 407.3136 D08516.gif Antidiabeti...1803) Protein digestion and absorption Transporter: ABCB1 [HSA:5243], SLC22A8 [HSA:9376] map07051 Antidiabeti

  7. Drug: D04541 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available ane insulin [DR:D04547] Antidiabetic [DS:H00408 H00409] Component of Humulin 70/30 (TN) insulin receptor ago...absorption CYP induction: CYP1A2 [HSA:1544] map07051 Antidiabetics USP drug classification [BR:br08302] Bloo

  8. Drug: D01400 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D01400 Drug Methyl parahydroxybenzoate (JP16); Methylparaben (NF); Methyl parahydro...xybenzoate (TN); Methylparaben (TN) C8H8O3 152.0473 152.1473 D01400.gif Pharmaceutic aid [antifungal agent] ...Component of Absorptive ointment [DR:D05354] map07110 Benzoic acid family CAS: 99-76-3 PubChem: 7848463 PDB-

  9. Clinical Drug-Drug Pharmacokinetic Interaction Potential of Sucralfate with Other Drugs: Review and Perspectives.

    Science.gov (United States)

    Sulochana, Suresh P; Syed, Muzeeb; Chandrasekar, Devaraj V; Mullangi, Ramesh; Srinivas, Nuggehally R

    2016-10-01

    Sucralfate, a complex of aluminium hydroxide with sulfated sucrose, forms a strong gastrointestinal tract (GIT) mucosal barrier with excellent anti-ulcer property. Because sucralfate does not undergo any significant oral absorption, sucralfate resides in the GIT for a considerable length of time. The unabsorbed sucralfate may alter the pharmacokinetics of the oral drugs by impeding its absorption and reducing the oral bioavailability. Because of the increased use of sucralfate, it was important to provide a reappraisal of the published clinical drug-drug interaction studies of sucralfate with scores of drugs. This review covers several category of drugs such as non-steroidal anti-inflammatory drugs, fluoroquinolones, histamine H2-receptor blockers, macrolides, anti-fungals, anti-diabetics, salicylic acid derivatives, steroidal anti-inflammatory drugs and provides pharmacokinetic data summary along with study design, objectives and key remarks. While the loss of oral bioavailability was significant for the fluoroquinolone class, it generally varied for other classes of drugs, suggesting that impact of the co-administration of sucralfate is manageable in clinical situations. Given the technology advancement in formulation development, it may be in order feasible to develop appropriate formulation strategies to either avoid or minimize the absorption-related issues when co-administered with sucralfate. It is recommended that consideration of both in vitro and preclinical studies may be in order to gauge the level of interaction of a drug with sucralfate. Such data may aid in the development of appropriate strategies to navigate the co-administration of sucralfate with other drugs in this age of polypharmacy.

  10. Food-drug interactions: Careful drug selection and patient counseling can reduce the risk in older patients.

    Science.gov (United States)

    Leibovitch, Eric R; Deamer, Robert L; Sanderson, Leslie A

    2004-03-01

    Older patients are at high risk for food-drug Interactions. These patients are commonly on multiple medications for chronic medical conditions. Age-related physiologic changes affecting drug absorption, distribution, metabolism and excretion, as well as drug action occur in these patients, and this variability in drug action may be further potentiated by interactions with foods. The most prominent interactions involve drug absorption from the GI tract; however alterations in drug metabolism are also highly significant. Food-drug interactions have been reported amongst a wide range of therapeutic drug classes, including, but not limited to, cardiovascular, psychoactive, anti-infective, endocrinologic, gastrointestinal, and respiratory agents. Health care providers can prevent significant drug therapy-related morbidity by carefully selecting drugs for geriatric patients and thoroughly counseling these patients about drug interactions with the foods they eat.

  11. Drug Facts

    Medline Plus

    Full Text Available ... some signs and symptoms of someone with a drug use problem? How Does Drug Use Become an Addiction? What ... Effects on the Body Drug Use Hurts Brains Drug Use and Mental Health Problems Often Happen Together The Link Between Drug Use ...

  12. DRUG-INTERACTIONS WITH QUINOLONE ANTIBACTERIALS

    NARCIS (Netherlands)

    BROUWERS, JRBJ

    1992-01-01

    The quinolone antibacterials are prone to many interactions with other drugs. Quinolone absorption is markedly reduced with antacids containing aluminium, magnesium and/or calcium and therapeutic failure may result. Other metallic ion-containing drugs, such as sucralfate, iron salts, and zinc salts,

  13. Sex Differences in Drug Abuse

    Science.gov (United States)

    Becker, Jill B.; Hu, Ming

    2008-01-01

    Sex differences are present for all of the phases of drug abuse (initiation, escalation of use, addiction, and relapse following abstinence). While there are some differences among specific classes of abused drugs, the general pattern of sex differences is the same for all drugs of abuse. Females begin regularly self-administering licit and illicit drugs of abuse at lower doses than do males, use escalates more rapidly to addiction, and females are at greater risk for relapse following abstinence. In this review, sex differences in drug abuse are discussed for humans and in animal models. The possible neuroendocrine mechanisms mediating these sex differences are discussed. PMID:17904621

  14. Mucoadhesive drug delivery system: An overview

    Directory of Open Access Journals (Sweden)

    Bindu M Boddupalli

    2010-01-01

    Full Text Available Mucoadhesive drug delivery systems interact with the mucus layer covering the mucosal epithelial surface, and mucin molecules and increase the residence time of the dosage form at the site of absorption. The drugs which have local action or those which have maximum absorption in gastrointestinal tract (GIT require increased duration of stay in GIT. Thus, mucoadhesive dosage forms are advantageous in increasing the drug plasma concentrations and also therapeutic activity. In this regard, this review covers the areas of mechanisms and theories of mucoadhesion, factors influencing the mucoadhesive devices and also various mucoadhesive dosage forms.

  15. 75 FR 33317 - Antibacterial Resistance and Diagnostic Device and Drug Development Research for Bacterial...

    Science.gov (United States)

    2010-06-11

    ... HUMAN SERVICES Food and Drug Administration Antibacterial Resistance and Diagnostic Device and Drug... resistance, rapid diagnostic device development for bacterial diseases, and antibacterial drug development. The workshop will address antibacterial drug resistance, mechanisms of resistance, epidemiology of...

  16. Stratum corneum damage and ex vivo porcine skin water absorption - a pilot study

    DEFF Research Database (Denmark)

    Duch Lynggaard, C; Bang Knudsen, D; Jemec, G B E

    2009-01-01

    A simple ex vivo screening technique would be of interest for mass screening of substances for potential barrier disruptive qualities. Ex vivo water absorption as a marker of skin barrier integrity was studied on pig ear skin. Skin water absorption was quantified by weighing and weight changes were...... found to reflect prehydration barrier damage. It is suggested that this simple model may be elaborated to provide a rapid, economical screening tool for potential skin irritants....

  17. Drug Facts

    Medline Plus

    Full Text Available ... to main content Easy-to-Read Drug Facts Search form Search Menu Home Drugs That People Abuse Alcohol Facts ... Past Drug Use Prevention Phone Numbers and Websites Search Share Government Shutdown Because of a lapse in ...

  18. Drug Facts

    Medline Plus

    Full Text Available ... time to find drug treatment centers near you. I want my daughter to avoid drugs. "Debbie" has ... addiction. Counseling is very helpful to her. All I wanted was more of the drug. "Max" was ...

  19. Drug Facts

    Medline Plus

    Full Text Available ... of someone with a drug use problem? How Does Drug Use Become an Addiction? What Makes Someone More Likely to Get Addicted to Drugs? Does Addiction Run in Families? Why Is It So ...

  20. Carotenoid absorption in chicken intestine.

    Science.gov (United States)

    Gómez, R; Alonso, A; Martín, M

    1978-09-01

    The powdered flowers of marigold (Tagetes erecta) are used as a cheap source of carotenoids in avicultura. Lutein (3,3'-dyhydroxi-alpha-carotene) constitutes up to 85 to 90% of marigold carotenoids. In the plant, lutein is found esterified to palmitic or estearic acid. In chicken, carotenoid is hydrolized in the first portion of the small intestine, and absorbed as free lutein. After the absorption, lutein is not re-esterified in the different chicken tissues.

  1. Geometrical interpretation of optical absorption

    Energy Technology Data Exchange (ETDEWEB)

    Monzon, J. J.; Barriuso, A. G.; Sanchez-Soto, L. L. [Departamento de Optica, Facultad de Fisica, Universidad Complutense, E-28040 Madrid (Spain); Montesinos-Amilibia, J. M. [Departamento de Geometria y Topologia, Facultad de Matematicas, Universidad Complutense, E-28040 Madrid (Spain)

    2011-08-15

    We reinterpret the transfer matrix for an absorbing system in very simple geometrical terms. In appropriate variables, the system appears as performing a Lorentz transformation in a (1 + 3)-dimensional space. Using homogeneous coordinates, we map that action on the unit sphere, which is at the realm of the Klein model of hyperbolic geometry. The effects of absorption appear then as a loxodromic transformation, that is, a rhumb line crossing all the meridians at the same angle.

  2. Multispectral Particle Absorption Monitor Project

    Data.gov (United States)

    National Aeronautics and Space Administration — This Small Business Innovation Research Phase II project concerns the development of a multi-wavelength monitor that will provide rapid, real-time measurement of the...

  3. Multispectral Particle Absorption Monitor Project

    Data.gov (United States)

    National Aeronautics and Space Administration — This Small Business Innovation Research Phase I project concerns the development of a multi-wavelength monitor that will provide rapid, real-time measurement of the...

  4. On the nature of absorption

    CERN Document Server

    Barger, V; Halzen, F

    1972-01-01

    The imaginary helicity non-flip omega exchange amplitudes in KN and NN scattering are determined versus t and s from data on elastic differential cross section differences. The omega -universality prediction Im omega /sub N/(t)= 3 Im omega /sub K/(t), is found to be satisfied for 0absorptive cuts as small t preserve universality. The impact parameter distributions of the omega amplitudes show: (i) a peripheral peak centred around b approximately=1 fm, with Delta b approximately =+or-0.5 fm in KN and Delta b approximately=+or-0.75 fm in NN; (ii) a sizeable negative contribution at small b, more negative in NN than in KN, (iii) a smaller tail of negative contributions around b approximately=2 fm. Strong absorption of the omega -pole imaginary amplitude with lambda values around two is needed to reproduced this structure. A new version of the absorption model suggested by pi N amplitude analysis, is confirmed by the results. (20 refs).

  5. Organizational forms and knowledge absorption

    Directory of Open Access Journals (Sweden)

    Radovanović Nikola

    2016-01-01

    Full Text Available Managing the entire portion of knowledge in an organization is a challenging task. At the organizational level, there can be enormous quantities of unknown, poorly valued or inefficiently applied knowledge. This is normally followed with the underdeveloped potential or inability of organizations to absorb knowledge from external sources. Facilitation of the efficient internal flow of knowledge within the established communication network may positively affect organizational capacity to absorb or identify, share and subsequently apply knowledge to commercial ends. Based on the evidences that the adoption of different organizational forms affects knowledge flows within an organization, this research analyzed the relationship between common organizational forms and absorptive capacity of organizations. In this paper, we test the hypothesis stating that the organizational structure affects knowledge absorption and exploitation in the organization. The methodology included quantitative and qualitative research method based on a questionnaire, while the data has been statistically analyzed and the hypothesis has been tested with the use of cross-tabulation and chi-square tests. The findings suggest that the type of organizational form affects knowledge absorption capacity and that having a less formalized and more flexible structure in an organization increases absorbing and exploiting opportunities of potentially valuable knowledge.

  6. Effect of microplastic deformation on the electron ultrasonic absorption in high-purity molybdenum monocrystals

    Energy Technology Data Exchange (ETDEWEB)

    Pal' -Val' , P.P.; Kaufmann, Kh.J.

    1983-03-01

    The low temperature (100-6 K) linear absorption of ultrasound (88 kHz) by high purity molybdenum single crystals have been studied. Both unstrained samples and samples sub ected to microplastic deformation (epsilon<=0.45%) were used. Unstrained samples displayed at T<30 K a rapid increase in the absorption with lowering temperature which is interpreted as an indication of electron viscosity due to electron-phonon collisions. After deformation this part of absorption disappeared. This seems to suggest that microplastic deformation brings about in the crystal a sufficiently large number of defects that can compete with phonons in restricting the electron mean free path. A low temperature dynamic annealing has been revealed in strained samples, that is almost complete recovery of the absorption nature under irradiation with high amplitude sound, epsilon/sub 0/ approximately 10/sup -4/, during 10 min, at 6 K. A new relaxation peak of absorption at 10 K has been found in strained samples.

  7. A rapid mitochondrial toxicity assay utilizing rapidly changing cell energy metabolism.

    Science.gov (United States)

    Sanuki, Yosuke; Araki, Tetsuro; Nakazono, Osamu; Tsurui, Kazuyuki

    2017-01-01

    Drug-induced liver injury is a major cause of safety-related drug-marketing withdrawals. Several drugs have been reported to disrupt mitochondrial function, resulting in hepatotoxicity. The development of a simple and effective in vitro assay to identify the potential for mitochondrial toxicity is thus desired to minimize the risk of causing hepatotoxicity and subsequent drug withdrawal. An in vitro test method called the "glucose-galactose" assay is often used in drug development but requires prior-culture of cells over several passages for mitochondrial adaptation, thereby restricting use of the assay. Here, we report a rapid version of this method with the same predictability as the original method. We found that replacing the glucose in the medium with galactose resulted in HepG2 cells immediately shifting their energy metabolism from glycolysis to oxidative phosphorylation due to drastic energy starvation; in addition, the intracellular concentration of ATP was reduced by mitotoxicants when glucose in the medium was replaced with galactose. Using our proposed rapid method, mitochondrial dysfunction in HepG2 cells can be evaluated by drug exposure for one hour without a pre-culture step. This rapid assay for mitochondrial toxicity may be more suitable for high-throughput screening than the original method at an early stage of drug development.

  8. Effect of age and diet on total and paracellular glucose absorption in nestling house sparrows.

    Science.gov (United States)

    Brzek, Paweł; Caviedes-Vidal, Enrique; Hoefer, Keeshia; Karasov, William H

    2010-01-01

    Size and hydrolytic activity of the gastrointestinal tracts of altricial birds undergo large and rapid changes during ontogeny. However, nothing is known about the development of the capacity of absorption of products of digestion, a factor that can limit total digestive performance. Using pharmacokinetic methods applied to wild-collected and laboratory-raised altricial nestlings of house sparrows (Passer domesticus), we addressed several questions of general significance about absorption in young birds. We found that both rate and efficiency of absorption of radiolabeled 3-O-methyl-D-glucose (3-OMD-glucose; absorbed by both transporter-mediated and nonmediated mechanisms) increased significantly between days 3 and 12 posthatch. We hypothesize that these changes can explain improvements in whole-diet digestion rate and efficiency observed in the young of house sparrows and of many other avian species, even after intestinal growth has ceased. We also tested the hypothesis that a high level of nonmediated, paracellular glucose absorption, as is typical in adult house sparrows, would already be observed in nestlings, and that their glucose absorption efficiency would not depend on glucose load because absorption rate is nonsaturable and is matched to substrate concentration. Using l-glucose (which is absorbed by nonmediated mechanism[s]), we found that, as predicted, paracellular absorption accounted for the majority of total absorption in nestlings of all ages, and starch content (0% vs. 25%) in the diet of laboratory-raised nestlings had no effect on efficiency of absorption of 3-OMD-glucose. Presumably, reliance on nonmediated absorption in young sparrows can save energy for growth. Also, during the transition from an almost starch-free, insect-based diet during the first days posthatch to the starch-rich, seed-based diet that is typical of adults, reliance on passive absorption is advantageous because the rate of absorption can easily match the current

  9. Simulation of solar-powered absorption cooling system

    Energy Technology Data Exchange (ETDEWEB)

    Atmaca, I.; Yigit, A. [Uludag Univ., Bursa (Turkey). Dept. of Mechanical Engineering

    2003-07-01

    With developing technology and the rapid increase in world population, the demand for energy is ever increasing. Conventional energy will not be enough to meet the continuously increasing need for energy in the future. In this case, renewable energy sources will become important. Solar energy is a very important energy source because of its advantages. Instead of a compressor system, which uses electricity, an absorption cooling system, using renewable energy and kinds of waste heat energy, may be used for cooling. In this study, a solar-powered, single stage, absorption cooling system, using a water-lithium bromide solution, is simulated. A modular computer program has been developed for the absorption system to simulate various cycle configurations and solar energy parameters for Antalya, Turkey. So, the effects of hot water inlet temperatures on the coefficient of performance (COP) and the surface area of the absorption cooling components are studied. In addition, reference temperatures which are the minimum allowable hot water inlet temperatures are determined and their effect on the fraction of the total load met by non-purchased energy (FNP) and the coefficient of performance are researched. Also, the effects of the collector type and storage tank mass are investigated in detail. (author)

  10. Absorption and metabolism of yerba mate phenolic compounds in humans.

    Science.gov (United States)

    Gómez-Juaristi, Miren; Martínez-López, Sara; Sarria, Beatriz; Bravo, Laura; Mateos, Raquel

    2018-02-01

    Bioavailability of yerba mate phenolic compounds was assessed in healthy humans. More than 34 metabolites were identified in biological fluids, mainly sulfated conjugates of caffeic and ferulic/isoferulic acids, in addition to non-metabolized caffeoyl-, feruloyl- and p-coumaroilquinic acids, with rapid appearance and clearance in plasma indicative of small intestinal absorption. These compounds amounted to 13.1% of the urinary metabolites. Delayed absorption of dihydrocaffeic, dihydroferulic and dihydrocoumaric acids and their phase II metabolites, in addition to feruloylglycine, pointed to their microbial origin and colonic absorption, accounting for 81.0% of excreted metabolites. Phase II flavonol metabolites (0.2%) derived mainly from rutin after colonic transformation and absorption were also detected. Additionally, dihydroferuloyl-, dihydrocaffeoyl- and dihydrocoumaroylquinic acids (5.7%) were identified, showing the most delayed kinetics. Total phenolic excretion (147.6μmol) corresponded to 13.2% of ingested phenols. In conclusion, yerba mate polyphenols are partially bioavailable and extensively metabolized, mainly by the colonic microbiota. Copyright © 2017. Published by Elsevier Ltd.

  11. Emission and Absorption Entropy Generation in Semiconductors

    OpenAIRE

    Reck, Kasper; Varpula, Aapo; Prunnila, Mika; Hansen, Ole

    2013-01-01

    While emission and absorption entropy generation is well known in black bodies, it has not previously been studied in semiconductors, even though semiconductors are widely used for solar light absorption in modern solar cells [1]. We present an analysis of the entropy generation in semiconductor materials due to emission and absorption of electromagnetic radiation. It is shown that the emission and absorption entropy generation reduces the fundamental limit on the efficiency of any semiconduc...

  12. TRANSDERMAL DRUG DELIVERY SYSTEMS: AN OVERVIEW

    OpenAIRE

    Ahmed, Azhar; Karki, Nirmal; Charde, Rita; Charde, Manoj; Gandhare, Bhushan

    2010-01-01

    With the advent of modern era of pharmaceutical dosage forms, transdermal drug delivery system (TDDS) established itself as an integral part of novel drug delivery systems. Transdermal patches are polymeric formulations which when applied to skin deliver the drug at a predetermined rate across dermis to achieve systemic effects. Transdermal dosage forms, though a costly alternative to conventional formulations, are becoming popular because of their unique advantages. Controlled absorption, mo...

  13. Mucus as a barrier to lipophilic drugs.

    Science.gov (United States)

    Sigurdsson, Hakon H; Kirch, Julian; Lehr, Claus-Michael

    2013-08-30

    Mucus is a complex hydrogel, comprising glycoproteins, lipids, salts, DNA, enzymes and cellular debris, covering many epithelial surfaces in the human body. Once secreted, mucin forms a barrier to protect the underlying tissues against the extracellular environment. Mucus can therefore adversely affect the absorption or action of drugs administered by the oral, pulmonary, vaginal, nasal or other routes. Solubility and lipophilicity are key factors determining drug absorption, as a drug has to be soluble in the body fluids at the site of absorption and must also possess enough lipophilicity to permeate the biological membrane. Evidence has accumulated over the past 40 years indicating that poorly soluble drugs will interact with mucus glycoprotein. Studies of the permeability of native or purified mucous gels are important when it comes to understanding the relative importance of hindered diffusion versus drug binding in mucous layers. This review highlights the current understanding of the drug-mucin interaction and also examines briefly the interaction of polymers and particles with the mucus matrix. While the concept of mucoadhesion was thought to provide an intensified and prolonged contact to mucosal absorption sites, mucopenetrating properties are nowadays being discussed for (nano)particulate carriers to overcome the mucus as a barrier and enhance drug delivery through mucus. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. Cinchocaine hydrochloride determination by atomic absorption spectrometry and spectrophotometry.

    Science.gov (United States)

    Abdel-Ghani, Nour T; Youssef, Ahmed F A; Awady, Mohamed A

    2005-05-01

    Two sensitive spectrophotometric and atomic absorption spectrometric procedures have been developed for determination of cinchocaine hydrochloride (Cin.Cl) in pure form and in pharmaceutical formulation. The spectrophotometric method was based on formation of an insoluble colored ion-associate between the cited drug and tetrathiocyanatocobaltate (CoTC) or hexathiocyanatochromate (CrTC) which dissolved and extracted in an organic solvent. The optimal experimental conditions for quantitative extraction such as pH, concentration of the reagents and solvent were studied. Toluene and iso-butyl alcohol proved to be the most suitable solvents for quantitative extraction of Cin-CoTC and Cin-CrTC ion-associates with maximum absorbance at 620 and 555 nm, respectively. The optimum concentration ranges, molar absorptivities, Ringbom ranges and Sandell sensitivities were also evaluated. The atomic absorption spectrometric method is based on measuring of the excess cobalt or chromium in the aqueous solution, after precipitation of the drug, at 240.7 and 357.9 nm, respectively. Linear application ranges, characteristic masses and detection limits were 57.99-361.9, 50.40 and 4.22 microg ml(-1) of Cin.Cl, in case of CoTC, while 37.99-379.9, 18.94 and 0.81 microg ml(-1) in case of CrTC.

  15. Prediction of Human Intestinal Absorption of Compounds Using Artificial Intelligence Techniques.

    Science.gov (United States)

    Kumar, Rajnish; Sharma, Anju; Siddiqui, Mohammed Haris; Tiwari, Rajesh Kumar

    2017-01-01

    Information about Pharmacokinetics of compounds is an essential component of drug design and development. Modeling the pharmacokinetic properties require identification of the factors effecting absorption, distribution, metabolism and excretion of compounds. There have been continuous attempts in the prediction of intestinal absorption of compounds using various Artificial intelligence methods in the effort to reduce the attrition rate of drug candidates entering to preclinical and clinical trials. Currently, there are large numbers of individual predictive models available for absorption using machine learning approaches. Six Artificial intelligence methods namely, Support vector machine, k- nearest neighbor, Probabilistic neural network, Artificial neural network, Partial least square and Linear discriminant analysis were used for prediction of absorption of compounds. Prediction accuracy of Support vector machine, k- nearest neighbor, Probabilistic neural network, Artificial neural network, Partial least square and Linear discriminant analysis for prediction of intestinal absorption of compounds was found to be 91.54%, 88.33%, 84.30%, 86.51%, 79.07% and 80.08% respectively. Comparative analysis of all the six prediction models suggested that Support vector machine with Radial basis function based kernel is comparatively better for binary classification of compounds using human intestinal absorption and may be useful at preliminary stages of drug design and development. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  16. Rapidly disintegrating vagina retentive cream suppositories of progesterone: development, patient satisfaction and in vitro/in vivo studies.

    Science.gov (United States)

    Bendas, Ehab Rasmy; Basalious, Emad B

    2016-01-01

    Our objective was to develop novel vagina retentive cream suppositories (VRCS) of progesterone having rapid disintegration and good vaginal retention. VRCS of progesterone were prepared using oil in water (o/w) emulsion of mineral oil or theobroma oil in hard fat and compared with conventional vaginal suppositories (CVS) prepared by hard fat. VRCS formulations were tested for content uniformity, disintegration, melting range, in vitro release and stability studies. The most stable formulation (VRCS I) was subjected to scaling-up manufacturing and patients' satisfaction test. The rapid disintegration, good retentive properties are applicable through the inclusion of emulsified theobroma oil rather than hydrophilic surfactant into the hard fat bases. The release profile of progesterone from VRCS I showed a biphasic pattern due to the formation of progesterone reservoir in the emulsified theobroma oil. All volunteers involved in patients' satisfaction test showed high satisfactory response to the tested formulation (VRCS). The in vivo pharmacokinetic study suggests that VRCS of progesterone provided higher rate and extent of absorption compared to hard fat based suppositories. Our results proposed that emulsified theobroma oil could be promising to solve the problems of poor patients' satisfaction and variability of drug absorption associated with hard fat suppositories.

  17. Drug Facts

    Medline Plus

    Full Text Available ... Body Drug Use Hurts Brains Drug Use and Mental Health Problems Often Happen Together The Link Between Drug Use and HIV/AIDS Treatment & Recovery Why Does a Person Need Treatment? Does Drug Treatment Work? What Are the Treatment Options? What Is Recovery? ...

  18. Molecular dynamics study on DNA nanotubes as drug delivery vehicle for anticancer drugs.

    Science.gov (United States)

    Liang, Lijun; Shen, Jia-Wei; Wang, Qi

    2017-05-01

    In recent years, self-assembled DNA nanotubes have emerged as a type of nano-biomaterials with great potential for biomedical applications. To develop universal nanocarriers for smart and targeted drug delivery from DNA nanotubes, the understanding of interaction mechanism between DNA nanotubes and drugs is essential. In this study, the interactions between anti-cancer drugs and DNA nanotubes were investigated via molecular dynamics simulation. Our simulation results demonstrated that the DNA nanotubes could serve as a good drug delivery material by absorption of anti-cancer drugs with π-π interactions. At high concentration of anti-cancer drugs, most of the drugs could be absorbed by DNA nanotubes. Therefore, it could greatly decrease the aggregation of anti-cancer drugs in aqueous solution. In addition, the stability of DNA nanotubes could be improved with the absorption of anti-cancer drugs. These findings greatly enhance the understanding of the interaction mechanism of DNA nanotubes and anti-cancer drugs. Our study suggests that DNA nanotubes are promising delivery vehicles by strong absorption of anti-cancer drugs. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Multifunctional High Drug Loading Nanocarriers for Cancer Drug Delivery

    Science.gov (United States)

    Jin, Erlei

    2011-12-01

    Most anticancer drugs have poor water-solubility, rapid blood clearance, low tumor-selectivity and severe systemic toxicity to healthy tissues. Thus, polymeric nanocarriers have been widely explored for anticancer drugs to solve these problems. However, polymer nanocarriers developed to date still suffer drawbacks including low drug loading contents, premature drug release, slow cellular internalization, slow intracellular drug release and thereby low therapeutic efficiency in cancer thermotherapy. Accordingly, in this dissertation, functional nanocapsules and nanoparticles including high drug loading liposome-like nanocapsules, high drug loading phospholipid-mimic nanocapsules with fast intracellular drug release, high drug loading charge-reversal nanocapsules, TAT based long blood circulation nanoparticles and charge-reversal nuclear targeted nanoparticles are designed and synthesized. These functional carriers have advantages such as high drug loading contents without premature drug release, fast cellular internalization and intracellular drug release, nuclear targeted delivery and long blood circulation. As a result, all these drug carriers show much higher in vitro and in vivo anti-cancer activities.

  20. Rapid Prototyping Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — The ARDEC Rapid Prototyping (RP) Laboratory was established in December 1992 to provide low cost RP capabilities to the ARDEC engineering community. The Stratasys,...

  1. Restoring the Architecture: A Rapid Clinical Perspective on Bone ...

    African Journals Online (AJOL)

    Restoring the Architecture: A Rapid Clinical Perspective on Bone-Mineral Density and Osteoporosis. 23. The page number in the footer is not for bibliographic referencing www.tandfonline.com/oemd. 23. • Vitamin D: Vital for calcium and phosphate absorption. Speculated to exert direct effects on bone, but the relevance of.

  2. Drug testing in oral fluid.

    Science.gov (United States)

    Drummer, Olaf H

    2006-08-01

    Over the last decade there have been considerable developments in the use of oral fluid (saliva) for drug testing. Oral fluid can provide a quick and non-invasive specimen for drug testing. However, its collection may be thwarted by lack of available fluid due to a range of physiological factors, including drug use itself. Food and techniques designed to stimulate production of oral fluid can also affect the concentration of drugs. Current applications are mainly focused on drugs of abuse testing in employees at workplaces where drug use has safety implications, in drivers of vehicles at the roadside and in other situations where drug impairment is suspected. Testing has included alcohol (ethanol) and a range of clinical tests eg antibodies to HIV, therapeutic drugs and steroids. Its main application has been for testing for drugs of abuse such as the amphetamines, cocaine and metabolites, opioids such as morphine, methadone and heroin, and for cannabis. Oral fluid concentrations of basic drugs such as the amphetamines, cocaine and some opioids are similar or higher than those in plasma. Tetrahydrocannabinol (THC), the major species present from cannabis use, displays similar concentrations in oral fluid compared to blood in the elimination phase. However, there is significant local absorption of the drug in the oral cavity which increases the concentrations for a period after use of drug. Depot effects occur for other drugs introduced into the body that allow local absorption, such as smoking of tobacco (nicotine), cocaine, amphetamines, or use of sub-lingual buprenorphine. Screening techniques are usually an adaptation of those used in other specimens, with an emphasis on the parent drug since this is usually the dominant species present in oral fluid. Confirmatory techniques are largely based on mass spectrometry (MS) with an emphasis on Liquid Chromatography-Mass Spectrometry (LC-MS), due to low sample volumes and the low detection limits required. Drug testing

  3. Phytases for Improved Iron Absorption

    DEFF Research Database (Denmark)

    Nielsen, Anne Veller Friis; Nyffenegger, Christian; Meyer, Anne S.

    2014-01-01

    Microbial phytases (EC 3.1.3.8) catalyse dephosphorylation of phytic acid, which is the primary storage compound for phosphorous in cereal kernels. The negatively charged phosphates in phytic acid chelate iron (Fe3+) and thus retards iron bioavailability in humans 1. Supplementation of microbial...... phytase can improve iron absorption from cereal-based diets 2. In order for phytase to catalyse iron release in vivo the phytase must be robust to low pH and proteolysis in the gastric ventricle. Our work has compared the robustness of five different microbial phytases, evaluating thermal stability...

  4. Carbon Dioxide Absorption Heat Pump

    Science.gov (United States)

    Jones, Jack A. (Inventor)

    2002-01-01

    A carbon dioxide absorption heat pump cycle is disclosed using a high pressure stage and a super-critical cooling stage to provide a non-toxic system. Using carbon dioxide gas as the working fluid in the system, the present invention desorbs the CO2 from an absorbent and cools the gas in the super-critical state to deliver heat thereby. The cooled CO2 gas is then expanded thereby providing cooling and is returned to an absorber for further cycling. Strategic use of heat exchangers can increase the efficiency and performance of the system.

  5. Mössbauer study of Chinese ancient mineral drugs

    Science.gov (United States)

    Qin, Guangyong; Li, Shi

    1992-04-01

    About 100 crude Chinese mineral drug samples were investigated with Mossbauer spectroscopy, X-ray diffraction analysis and atomic absorption spectroscopy. The classifications, species and components of Chinese mineral drugs will be elucidated. The pharmaceutic and curative mechanisms of these mineral drugs will be discussed.

  6. Analysis of adverse drug reactions using drug and drug target interactions and graph-based methods.

    Science.gov (United States)

    Lin, Shih-Fang; Xiao, Ke-Ting; Huang, Yu-Ting; Chiu, Chung-Cheng; Soo, Von-Wun

    2010-01-01

    The purpose of this study was to integrate knowledge about drugs, drug targets, and topological methods. The goals were to build a system facilitating the study of adverse drug events, to make it easier to find possible explanations, and to group similar drug-drug interaction cases in the adverse drug reaction reports from the US Food and Drug Administration (FDA). We developed a system that analyses adverse drug reaction (ADR) cases reported by the FDA. The system contains four modules. First, we integrate drug and drug target databases that provide information related to adverse drug reactions. Second, we classify drug and drug targets according to anatomical therapeutic chemical classification (ATC) and drug target ontology (DTO). Third, we build drug target networks based on drug and drug target databases. Finally, we apply topological analysis to reveal drug interaction complexity for each ADR case reported by the FDA. We picked 1952 ADR cases from the years 2005-2006. Our dataset consisted of 1952 cases, of which 1471 cases involved ADR targets, 845 cases involved absorption, distribution, metabolism, and excretion (ADME) targets, and 507 cases involved some drugs acting on the same targets, namely, common targets (CTs). We then investigated the cases involving ADR targets, ADME targets, and CTs using the ATC system and DTO. In the cases that led to death, the average number of common targets (NCTs) was 0.879 and the average of average clustering coefficient (ACC) was 0.067. In cases that did not lead to death, the average NCTs was 0.551, and the average of ACC was 0.039. We implemented a system that can find possible explanations and cluster similar ADR cases reported by the FDA. We found that the average of ACC and the average NCTs in cases leading to death are higher than in cases not leading to death, suggesting that the interactions in cases leading to death are generally more complicated than in cases not leading to death. This indicates that our system

  7. Mechanistic Oral Absorption Modeling and Simulation for Formulation Development and Bioequivalence Evaluation: Report of an FDA Public Workshop.

    Science.gov (United States)

    Zhang, X; Duan, J; Kesisoglou, F; Novakovic, J; Amidon, G L; Jamei, M; Lukacova, V; Eissing, T; Tsakalozou, E; Zhao, L; Lionberger, R

    2017-08-01

    On May 19, 2016, the US Food and Drug Administration (FDA) hosted a public workshop, entitled "Mechanistic Oral Absorption Modeling and Simulation for Formulation Development and Bioequivalence Evaluation." The topic of mechanistic oral absorption modeling, which is one of the major applications of physiologically based pharmacokinetic (PBPK) modeling and simulation, focuses on predicting oral absorption by mechanistically integrating gastrointestinal transit, dissolution, and permeation processes, incorporating systems, active pharmaceutical ingredient (API), and the drug product information, into a systemic mathematical whole-body framework. © 2017 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

  8. High-throughput liquid-absorption air-sampling apparatus and methods

    Science.gov (United States)

    Zaromb, Solomon

    2000-01-01

    A portable high-throughput liquid-absorption air sampler [PHTLAAS] has an asymmetric air inlet through which air is drawn upward by a small and light-weight centrifugal fan driven by a direct current motor that can be powered by a battery. The air inlet is so configured as to impart both rotational and downward components of motion to the sampled air near said inlet. The PHTLAAS comprises a glass tube of relatively small size through which air passes at a high rate in a swirling, highly turbulent motion, which facilitates rapid transfer of vapors and particulates to a liquid film covering the inner walls of the tube. The pressure drop through the glass tube is water, usually water. The sampler's collection efficiency is usually >20% for vapors or airborne particulates in the 2-3.mu. range and >50% for particles larger than 4.mu.. In conjunction with various analyzers, the PHTLAAS can serve to monitor a variety of hazardous or illicit airborne substances, such as lead-containing particulates, tritiated water vapor, biological aerosols, or traces of concealed drugs or explosives.

  9. Characterization of particulate drug delivery systems for oral delivery of Peptide and protein drugs

    DEFF Research Database (Denmark)

    Christophersen, Philip Carsten; Fano, Mathias; Saaby, Lasse

    2015-01-01

    Oral drug delivery is a preferred route because of good patient compliance. However, most peptide/ protein drugs are delivered via parenteral routes because of the absorption barriers in the gastrointestinal (GI) tract such as enzymatic degradation by proteases and low permeability acrossthe biol...

  10. Iodine Absorption Cells Purity Testing

    Directory of Open Access Journals (Sweden)

    Jan Hrabina

    2017-01-01

    Full Text Available This article deals with the evaluation of the chemical purity of iodine-filled absorption cells and the optical frequency references used for the frequency locking of laser standards. We summarize the recent trends and progress in absorption cell technology and we focus on methods for iodine cell purity testing. We compare two independent experimental systems based on the laser-induced fluorescence method, showing an improvement of measurement uncertainty by introducing a compensation system reducing unwanted influences. We show the advantages of this technique, which is relatively simple and does not require extensive hardware equipment. As an alternative to the traditionally used methods we propose an approach of hyperfine transitions’ spectral linewidth measurement. The key characteristic of this method is demonstrated on a set of testing iodine cells. The relationship between laser-induced fluorescence and transition linewidth methods will be presented as well as a summary of the advantages and disadvantages of the proposed technique (in comparison with traditional measurement approaches.

  11. Circumgalactic Oxygen Absorption and Feedback

    Science.gov (United States)

    Mathews, William G.; Prochaska, J. Xavier

    2017-09-01

    O vi absorption in quasar spectra caused by intervening circumgalactic atmospheres suggests a downturn in the atmospheric column density in sightlines passing beyond about 100 kpc from central star-forming galaxies. This turnover supports the hypothesis that the oxygen originates in the central galaxies. When converted into oxygen space density using an Abel integral inversion, the O vi columns require ≳ {10}9 M ⊙ of oxygen concentrated near 100 kpc. Circumgalactic gas within this radius cools in less than 1 Gyr and radiates ˜ {10}42.2 erg s-1 overall. The feedback power necessary to maintain such oxygen-rich atmospheres for many Gyr cannot be easily supplied by galactic supernovae. However, massive central black holes in star-forming galaxies may generate sufficient accretion power and intermittent shock waves at r˜ 100 {kpc} to balance circumgalactic radiation losses in late-type {L}\\star galaxies. The relative absence of O vi absorption observed in early-type, passive {L}\\star galaxies may arise from enhanced AGN feedback from their more massive central black holes.

  12. Iron Absorption in Drosophila melanogaster

    Directory of Open Access Journals (Sweden)

    Fanis Missirlis

    2013-05-01

    Full Text Available The way in which Drosophila melanogaster acquires iron from the diet remains poorly understood despite iron absorption being of vital significance for larval growth. To describe the process of organismal iron absorption, consideration needs to be given to cellular iron import, storage, export and how intestinal epithelial cells sense and respond to iron availability. Here we review studies on the Divalent Metal Transporter-1 homolog Malvolio (iron import, the recent discovery that Multicopper Oxidase-1 has ferroxidase activity (iron export and the role of ferritin in the process of iron acquisition (iron storage. We also describe what is known about iron regulation in insect cells. We then draw upon knowledge from mammalian iron homeostasis to identify candidate genes in flies. Questions arise from the lack of conservation in Drosophila for key mammalian players, such as ferroportin, hepcidin and all the components of the hemochromatosis-related pathway. Drosophila and other insects also lack erythropoiesis. Thus, systemic iron regulation is likely to be conveyed by different signaling pathways and tissue requirements. The significance of regulating intestinal iron uptake is inferred from reports linking Drosophila developmental, immune, heat-shock and behavioral responses to iron sequestration.

  13. Iron Absorption in Drosophila melanogaster

    Science.gov (United States)

    Mandilaras, Konstantinos; Pathmanathan, Tharse; Missirlis, Fanis

    2013-01-01

    The way in which Drosophila melanogaster acquires iron from the diet remains poorly understood despite iron absorption being of vital significance for larval growth. To describe the process of organismal iron absorption, consideration needs to be given to cellular iron import, storage, export and how intestinal epithelial cells sense and respond to iron availability. Here we review studies on the Divalent Metal Transporter-1 homolog Malvolio (iron import), the recent discovery that Multicopper Oxidase-1 has ferroxidase activity (iron export) and the role of ferritin in the process of iron acquisition (iron storage). We also describe what is known about iron regulation in insect cells. We then draw upon knowledge from mammalian iron homeostasis to identify candidate genes in flies. Questions arise from the lack of conservation in Drosophila for key mammalian players, such as ferroportin, hepcidin and all the components of the hemochromatosis-related pathway. Drosophila and other insects also lack erythropoiesis. Thus, systemic iron regulation is likely to be conveyed by different signaling pathways and tissue requirements. The significance of regulating intestinal iron uptake is inferred from reports linking Drosophila developmental, immune, heat-shock and behavioral responses to iron sequestration. PMID:23686013

  14. Development and evaluation of an in vitro vaginal model for assessment of drug's biopharmaceutical properties: curcumin

    National Research Council Canada - National Science Library

    Berginc, Katja; Skalko-Basnet, Nataša; Basnet, Purusotam; Kristl, Albin

    2012-01-01

    Vaginal administration is a promising alternative to the per-oral route in achieving systemic or local therapeutic effects, when intestinal drug absorption is hindered by problematic biopharmaceutical drug properties...

  15. Transport mechanism of lipid covered saquinavir pure drug nanoparticles in intestinal epithelium

    DEFF Research Database (Denmark)

    Xia, Dengning; He, Yuan; Li, Qiuxia

    2018-01-01

    Pure drug nanoparticles (NPs) represent a promising formulation for improved drug solubility and controlled dissolution velocity. However, limited absorption by the intestinal epithelium remains challenge to their clinical application, and little is known about how these NPs within the cells...

  16. Clinical pharmacokinetic and pharmacodynamic properties of drugs used in the treatment of Parkinson's disease.

    Science.gov (United States)

    Deleu, Dirk; Northway, Margaret G; Hanssens, Yolande

    2002-01-01

    Current research in Parkinson's disease (PD) focuses on symptomatic therapy and neuroprotective interventions. Drugs that have been used for symptomatic therapy are levodopa, usually combined with a peripheral decarboxylase inhibitor, synthetic dopamine receptor agonists, centrally-acting antimuscarinic drugs, amantadine, monoamine oxidase-B (MAO-B) inhibitors and catechol-O-methyltransferase (COMT) inhibitors. Drugs for which there is at least some evidence for neuroprotective effect are certain dopamine agonists, amantadine and MAO-B inhibitors (selegiline). Levodopa remains the most effective drug for the treatment of PD. Several factors contribute to the complex clinical pharmacokinetics of levodopa: erratic absorption, short half-life, peripheral O-methylation and facilitated transport across the blood-brain barrier. In patients with response fluctuations to levodopa, the concentration-effect curve becomes steeper and shifts to the right compared with patients with stable response. Pharmacokinetic-pharmacodynamic modelling can affect decisions regarding therapeutic strategies. The dopamine agonists include ergot derivatives (bromocriptine, pergolide, lisuride and cabergoline), non-ergoline derivatives (pramipexole, ropinirole and piribedil) and apomorphine. Most dopamine agonists have their specific pharmacological profile. They are used in monotherapy and as an adjunct to levodopa in early and advanced PD. Few pharmacokinetic and pharmacodynamic data are available regarding centrally acting antimuscarinic drugs. They are characterised by rapid absorption after oral intake, large volume of distribution and low clearance relative to hepatic blood flow, with extensive metabolism. The mechanism of action of amantadine remains elusive. It is well absorbed and widely distributed. Since elimination is primarily by renal clearance, accumulation of the drug can occur in patients with renal dysfunction and dosage reduction must be envisaged. The COMT inhibitors

  17. Drug resistance mechanisms and novel drug targets for tuberculosis therapy.

    Science.gov (United States)

    Islam, Md Mahmudul; Hameed, H M Adnan; Mugweru, Julius; Chhotaray, Chiranjibi; Wang, Changwei; Tan, Yaoju; Liu, Jianxiong; Li, Xinjie; Tan, Shouyong; Ojima, Iwao; Yew, Wing Wai; Nuermberger, Eric; Lamichhane, Gyanu; Zhang, Tianyu

    2017-01-20

    Drug-resistant tuberculosis (TB) poses a significant challenge to the successful treatment and control of TB worldwide. Resistance to anti-TB drugs has existed since the beginning of the chemotherapy era. New insights into the resistant mechanisms of anti-TB drugs have been provided. Better understanding of drug resistance mechanisms helps in the development of new tools for the rapid diagnosis of drug-resistant TB. There is also a pressing need in the development of new drugs with novel targets to improve the current treatment of TB and to prevent the emergence of drug resistance in Mycobacterium tuberculosis. This review summarizes the anti-TB drug resistance mechanisms, furnishes some possible novel drug targets in the development of new agents for TB therapy and discusses the usefulness using known targets to develop new anti-TB drugs. Whole genome sequencing is currently an advanced technology to uncover drug resistance mechanisms in M. tuberculosis. However, further research is required to unravel the significance of some newly discovered gene mutations in their contribution to drug resistance. Copyright © 2016 Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Ltd. All rights reserved.

  18. NEW ANTIPLATELET DRUGS (PART 1

    Directory of Open Access Journals (Sweden)

    A. B. Sumarokov

    2016-01-01

    Full Text Available Antiplatelet agents are a necessary component of modern atherosclerosis therapy. The difficulties of antiplatelet treatment lie in the balance between the necessary therapeutic effect of the drug and the risk of excessive action leading to the bleeding. Possibility to control pharmacodynamics effects of antiplatelet agents is still very limited. Pharmacology of antiplatelet drugs is growing rapidly. Some of new antiplatelet drugs are on their way to clinical application — prasugrel, ticagrelor, elinogrel, inhibitors of thromboxane and thrombin receptors. Clinical pharmacology of these drugs is different. This requires a doctor's good knowledge of their identity to avoid the development of iatrogenic complications.

  19. NEW ANTIPLATELET DRUGS (PART 1

    Directory of Open Access Journals (Sweden)

    A. B. Sumarokov

    2011-01-01

    Full Text Available Antiplatelet agents are a necessary component of modern atherosclerosis therapy. The difficulties of antiplatelet treatment lie in the balance between the necessary therapeutic effect of the drug and the risk of excessive action leading to the bleeding. Possibility to control pharmacodynamics effects of antiplatelet agents is still very limited. Pharmacology of antiplatelet drugs is growing rapidly. Some of new antiplatelet drugs are on their way to clinical application — prasugrel, ticagrelor, elinogrel, inhibitors of thromboxane and thrombin receptors. Clinical pharmacology of these drugs is different. This requires a doctor's good knowledge of their identity to avoid the development of iatrogenic complications.

  20. Rapid Airplane Parametric Input Design (RAPID)

    Science.gov (United States)

    Smith, Robert E.

    1995-01-01

    RAPID is a methodology and software system to define a class of airplane configurations and directly evaluate surface grids, volume grids, and grid sensitivity on and about the configurations. A distinguishing characteristic which separates RAPID from other airplane surface modellers is that the output grids and grid sensitivity are directly applicable in CFD analysis. A small set of design parameters and grid control parameters govern the process which is incorporated into interactive software for 'real time' visual analysis and into batch software for the application of optimization technology. The computed surface grids and volume grids are suitable for a wide range of Computational Fluid Dynamics (CFD) simulation. The general airplane configuration has wing, fuselage, horizontal tail, and vertical tail components. The double-delta wing and tail components are manifested by solving a fourth order partial differential equation (PDE) subject to Dirichlet and Neumann boundary conditions. The design parameters are incorporated into the boundary conditions and therefore govern the shapes of the surfaces. The PDE solution yields a smooth transition between boundaries. Surface grids suitable for CFD calculation are created by establishing an H-type topology about the configuration and incorporating grid spacing functions in the PDE equation for the lifting components and the fuselage definition equations. User specified grid parameters govern the location and degree of grid concentration. A two-block volume grid about a configuration is calculated using the Control Point Form (CPF) technique. The interactive software, which runs on Silicon Graphics IRIS workstations, allows design parameters to be continuously varied and the resulting surface grid to be observed in real time. The batch software computes both the surface and volume grids and also computes the sensitivity of the output grid with respect to the input design parameters by applying the precompiler tool