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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. Rapid screening and identification of illicit drugs by IR absorption spectroscopy and gas chromatography

    Science.gov (United States)

    Mengali, Sandro; Liberatore, Nicola; Luciani, Domenico; Viola, Roberto; Cardinali, Gian Carlo; Elmi, Ivan; Poggi, Antonella; Zampolli, Stefano; Biavardi, Elisa; Dalcanale, Enrico; Bonadio, Federica; Delemont, Olivier; Esseiva, Pierre; Romolo, Francesco S.

    2013-01-01

    Analytical instruments based on InfraRed Absorption Spectroscopy (IRAS) and Gas Chromatography (GC) are today available only as bench-top instrumentation for forensic labs and bulk analysis. Within the 'DIRAC' project funded by the European Commission, we are developing an advanced portable sensor, that combines miniaturized GC as its key chemical separation tool, and IRAS in a Hollow Fiber (HF) as its key analytical tool, to detect and recognize illicit drugs and key precursors, as bulk and as traces. The HF-IRAS module essentially consists of a broadly tunable External Cavity (EC) Quantum Cascade Laser (QCL), thermo-electrically cooled MCT detectors, and an infrared hollow fiber at controlled temperature. The hollow fiber works as a miniaturized gas cell, that can be connected to the output of the GC column with minimal dead volumes. Indeed, the module has been coupled to GC columns of different internal diameter and stationary phase, and with a Vapour Phase Pre-concentrator (VPC) that selectively traps target chemicals from the air. The presentation will report the results of tests made with amphetamines and precursors, as pure substances, mixtures, and solutions. It will show that the sensor is capable of analyzing all the chemicals of interest, with limits of detection ranging from a few nanograms to about 100-200 ng. Furthermore, it is suitable to deal with vapours directly trapped from the headspace of a vessel, and with salts treated in a basic solution. When coupled to FAST GC columns, the module can analyze multi-components mixes in less than 5 minutes.

  3. Polymeric nanoparticles for increased oral bioavailability and rapid absorption using celecoxib as a model of a low-solubility, high-permeability drug.

    Science.gov (United States)

    Morgen, Michael; Bloom, Corey; Beyerinck, Ron; Bello, Akintunde; Song, Wei; Wilkinson, Karen; Steenwyk, Rick; Shamblin, Sheri

    2012-02-01

    To demonstrate drug/polymer nanoparticles can increase the rate and extent of oral absorption of a low-solubility, high-permeability drug. Amorphous drug/polymer nanoparticles containing celecoxib were prepared using ethyl cellulose and either sodium caseinate or bile salt. Nanoparticles were characterized using dynamic light scattering, transmission and scanning electron microscopy, and differential scanning calorimetry. Drug release and resuspension studies were performed using high-performance liquid chromatography. Pharmacokinetic studies were performed in dogs and humans. A physical model is presented describing the nanoparticle state of matter and release performance. Nanoparticles dosed orally in aqueous suspensions provided higher systemic exposure and faster attainment of peak plasma concentrations than commercial capsules, with median time to maximum drug concentration (Tmax) of 0.75 h in humans for nanoparticles vs. 3 h for commercial capsules. Nanoparticles released celecoxib rapidly and provided higher dissolved-drug concentrations than micronized crystalline drug. Nanoparticle suspensions are stable for several days and can be spray-dried to form dry powders that resuspend in water. Drug/polymer nanoparticles are well suited for providing rapid oral absorption and increased bioavailability of BCS Class II drugs.

  4. Drug absorption from the irradiated rat small intestine in situ

    International Nuclear Information System (INIS)

    Venho, V.M.K.

    1976-01-01

    The absorption of acidic drugs phenobarbitone and sulphafurazole, basic drugs mecamylamine and quinidine, and a neutral drug isoniazid was studied in situ. Rats were irradiated 750 rad whole-body with 60 Co and the absorption experiment was done three and six days thereafter using the cannulated small intestine of urethane-anaesthetized rats. Drug disappearance from the intestinal lumen and drug levels in the whole blood and intestinal wall were measured. In control rats phenobarbitone showed the most rapid absorption and mecamylamine the slowest. Irradiation retarded the disappearance of all drugs from the intestinal lumen on the third postirradiation day. Fluid absorption was also diminished. On the sixth postirradiation day the absorption of phenobarbitone, sulphafurazole and mecamylamine had returned to the control level, but the absorption of quinidine and isoniazid was still retarded. After i.v. administration of drugs they were not significantly excreted into the intestinal contents and irradiation did not modify excretion. The distribution of drugs between the intestinal fluid and the intestinal wall was complete in the first 10 min of experiment. Mecamylamine and quinidine were lowered in the whole blood by irradiation. Blood levels of drugs did not correlate well to the rate of disappearance of drugs from the intestinal lumen. The reversible changes in absorption induced by irradiation are probably secondary effects of irradiation on intestinal morphology, permeability and transport capacity, composition, and possibly blood flow. (orig.) [de

  5. Effect of oils on drug absorption

    OpenAIRE

    Palin, K.J.

    1981-01-01

    Oil and emulsion vehicles have been shown to alter the oral absorption of many drugs. This may be due to enhanced lymph flow and/or altered gastro-intestinal motility in the presence of the oils. The oral absorption of a model compound (DOT) in the presence of three chemically different oils, arachis oil, Miglyol 812 and liquid paraffin was investigated in rats, the influence of lymphatic absorption and gastro-intestinal motility being determined. The findings were applied to the for.mulation...

  6. Systematic review: Helicobacter pylori infection and impaired drug absorption.

    Science.gov (United States)

    Lahner, E; Annibale, B; Delle Fave, G

    2009-02-15

    Impaired acid secretion may affect drug absorption and may be consequent to corporal Helicobacter pylori-gastritis, which may affect the absorption of orally administered drugs. To focus on the evidence of impaired drug absorption associated with H. pylori infection. Data sources were the systematic search of MEDLINE/EMBASE/SCOPUS databases (1980-April 2008) for English articles using the keywords: drug malabsorption/absorption, stomach, Helicobacter pylori, gastritis, gastric acid, gastric pH, hypochlorhydria, gastric hypoacidity. Study selection was made from 2099 retrieved articles, five studies were identified. Data were extracted from selected papers, investigated drugs, study type, main features of subjects, study design, intervention type and results were extracted. In all, five studies investigated impaired absorption of l-dopa, thyroxine and delavirdine in H. pylori infection. Eradication treatment led to 21-54% increase in l-dopa in Parkinson's disease. Thyroxine requirement was higher in hypochlorhydric goitre with H. pylori-gastritis and thyrotropin levels decreased by 94% after treatment. In H. pylori- and HIV-positive hypochlorhydric subjects, delavirdine absorption increased by 57% with orange juice administration and by 150% after eradication. A plausible mechanism of impaired drug absorption is decreased acid secretion in H. pylori-gastritis patients. Helicobacter pylori infection and hypochlorhydria should be considered in prescribing drugs the absorption of which is potentially affected by intragastric pH.

  7. A new in vitro lipid digestion - in vivo absorption model to evaluate the mechanisms of drug absorption from lipid-based formulations.

    Science.gov (United States)

    Crum, Matthew F; Trevaskis, Natalie L; Williams, Hywel D; Pouton, Colin W; Porter, Christopher J H

    2016-04-01

    In vitro lipid digestion models are commonly used to screen lipid-based formulations (LBF), but in vitro-in vivo correlations are in some cases unsuccessful. Here we enhance the scope of the lipid digestion test by incorporating an absorption 'sink' into the experimental model. An in vitro model of lipid digestion was coupled directly to a single pass in situ intestinal perfusion experiment in an anaesthetised rat. The model allowed simultaneous real-time analysis of the digestion and absorption of LBFs of fenofibrate and was employed to evaluate the influence of formulation digestion, supersaturation and precipitation on drug absorption. Formulations containing higher quantities of co-solvent and surfactant resulted in higher supersaturation and more rapid drug precipitation in vitro when compared to those containing higher quantities of lipid. In contrast, when the same formulations were examined using the coupled in vitro lipid digestion - in vivo absorption model, drug flux into the mesenteric vein was similar regardless of in vitro formulation performance. For some drugs, simple in vitro lipid digestion models may underestimate the potential for absorption from LBFs. Consistent with recent in vivo studies, drug absorption for rapidly absorbed drugs such as fenofibrate may occur even when drug precipitation is apparent during in vitro digestion.

  8. Rapid Assessment of Drugs of Abuse.

    Science.gov (United States)

    Wiencek, Joesph R; Colby, Jennifer M; Nichols, James H

    Laboratory testing for drugs of abuse has become standard practice in many settings both forensic and clinical. Urine is the predominant specimen, but other specimens are possible including hair, nails, sweat, and oral fluid. Point-of-care test kits provide for rapid analysis at the site where specimens are collected allowing for immediate action on the results. POCT is based on immunochromatography where the drug in the patient's sample competes with drug and antibody conjugates in the test to develop or block the development of a colored line. Most POCTs are visually interpreted in a few minutes. The potential for false positives is possible due to drug cross-reactivity with the antibodies in the test. False negatives are also possible due to dilution of the sample and the potential for adulteration or sample substitution by the patient. POCT shows more variability than central laboratory testing because of the variety of operators involved in the testing process, but POCT has good agreement for most tests with mass spectrometry provided comparable cutoffs and cross-reactivity of drugs/metabolites are considered. Validation of the test performance with the intended operators will identify potential interferences and operational issues before implementing the test in routine practice. POCT offers faster turnaround of test results provided the limitations and challenges of the test are considered. © 2017 Elsevier Inc. All rights reserved.

  9. Quantitation of small intestinal permeability during normal human drug absorption

    OpenAIRE

    Levitt, David G

    2013-01-01

    Background Understanding the quantitative relationship between a drug?s physical chemical properties and its rate of intestinal absorption (QSAR) is critical for selecting candidate drugs. Because of limited experimental human small intestinal permeability data, approximate surrogates such as the fraction absorbed or Caco-2 permeability are used, both of which have limitations. Methods Given the blood concentration following an oral and intravenous dose, the time course of intestinal absorpti...

  10. 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.

  11. In Silico Modeling of Gastrointestinal Drug Absorption: Predictive Performance of Three Physiologically Based Absorption Models.

    Science.gov (United States)

    Sjögren, Erik; Thörn, Helena; Tannergren, Christer

    2016-06-06

    Gastrointestinal (GI) drug absorption is a complex process determined by formulation, physicochemical and biopharmaceutical factors, and GI physiology. Physiologically based in silico absorption models have emerged as a widely used and promising supplement to traditional in vitro assays and preclinical in vivo studies. However, there remains a lack of comparative studies between different models. The aim of this study was to explore the strengths and limitations of the in silico absorption models Simcyp 13.1, GastroPlus 8.0, and GI-Sim 4.1, with respect to their performance in predicting human intestinal drug absorption. This was achieved by adopting an a priori modeling approach and using well-defined input data for 12 drugs associated with incomplete GI absorption and related challenges in predicting the extent of absorption. This approach better mimics the real situation during formulation development where predictive in silico models would be beneficial. Plasma concentration-time profiles for 44 oral drug administrations were calculated by convolution of model-predicted absorption-time profiles and reported pharmacokinetic parameters. Model performance was evaluated by comparing the predicted plasma concentration-time profiles, Cmax, tmax, and exposure (AUC) with observations from clinical studies. The overall prediction accuracies for AUC, given as the absolute average fold error (AAFE) values, were 2.2, 1.6, and 1.3 for Simcyp, GastroPlus, and GI-Sim, respectively. The corresponding AAFE values for Cmax were 2.2, 1.6, and 1.3, respectively, and those for tmax were 1.7, 1.5, and 1.4, respectively. Simcyp was associated with underprediction of AUC and Cmax; the accuracy decreased with decreasing predicted fabs. A tendency for underprediction was also observed for GastroPlus, but there was no correlation with predicted fabs. There were no obvious trends for over- or underprediction for GI-Sim. The models performed similarly in capturing dependencies on dose and

  12. A two-dimensional mathematical model of percutaneous drug absorption

    Directory of Open Access Journals (Sweden)

    Kubota K

    2004-06-01

    Full Text Available Abstract Background When a drug is applied on the skin surface, the concentration of the drug accumulated in the skin and the amount of the drug eliminated into the blood vessel depend on the value of a parameter, r. The values of r depend on the amount of diffusion and the normalized skin-capillary clearence. It is defined as the ratio of the steady-state drug concentration at the skin-capillary boundary to that at the skin-surface in one-dimensional models. The present paper studies the effect of the parameter values, when the region of contact of the skin with the drug, is a line segment on the skin surface. Methods Though a simple one-dimensional model is often useful to describe percutaneous drug absorption, it may be better represented by multi-dimensional models. A two-dimensional mathematical model is developed for percutaneous absorption of a drug, which may be used when the diffusion of the drug in the direction parallel to the skin surface must be examined, as well as in the direction into the skin, examined in one-dimensional models. This model consists of a linear second-order parabolic equation with appropriate initial conditions and boundary conditions. These boundary conditions are of Dirichlet type, Neumann type or Robin type. A finite-difference method which maintains second-order accuracy in space along the boundary, is developed to solve the parabolic equation. Extrapolation in time is applied to improve the accuracy in time. Solution of the parabolic equation gives the concentration of the drug in the skin at a given time. Results Simulation of the numerical methods described is carried out with various values of the parameter r. The illustrations are given in the form of figures. Conclusion Based on the values of r, conclusions are drawn about (1 the flow rate of the drug, (2 the flux and the cumulative amount of drug eliminated into the receptor cell, (3 the steady-state value of the flux, (4 the time to reach the steady

  13. Remote controlled capsules in human drug absorption (HDA) studies.

    Science.gov (United States)

    Wilding, Ian R; Prior, David V

    2003-01-01

    The biopharmaceutical complexity of today's new drug candidates provides significant challenges for pharmaceutical scientists in terms of both candidate selection and optimizing subsequent development strategy. In addition, life cycle management of marketed drugs has become an important income stream for pharmaceutical companies, but the selection of least risk/highest benefit strategies is far from simple. The proactive adoption of human drug absorption (HDA) studies using remote controlled capsules offers the pharmaceutical scientist significant guidance for planning a route through the maze of product development. This review examines the position of HDA studies in drug development, using a variety of case histories and an insightful update on remote controlled capsules to achieve site-specific delivery.

  14. 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.

  15. Rapid absorption of diclofenac and acetaminophen after their oral administration to cattle.

    Science.gov (United States)

    Sawaguchi, Akiyo; Sasaki, Kazuaki; Miyanaga, Keisuke; Nakayama, Mitsuhiro; Nagasue, Masato; Shimoda, Minoru

    2016-10-01

    The oral pharmacokinetics of diclofenac (DF) were evaluated in cattle by analyzing plasma concentration-time data after its intravenous and oral administration in order to propose the oral administration of DF as effective route to avoid long withdraw period. DF was intravenously and orally administered at 1 mg/kg to cattle using a crossover design with a 4-week washout period. Plasma concentrations of DF were determined by a HPLC analysis. The mean absorption time (MAT) and absorption half-life (t 1/2ka ) were 1.61 ± 0.61 and 1.51 ± 0.38 hr, respectively, and bioavailability was nearly 100%. The oral pharmacokinetics of acetaminophen (AAP) were also evaluated in cattle. Plasma concentrations of AAP were determined by a HPLC analysis. MAT and t 1/2ka were 2.85 ± 0.93 and 1.53 ± 0.28 hr, respectively, and bioavailability was approximately 70%. In conclusion, the results of the present study indicate that DF and AAP are rapidly absorbed from the forestomach of cattle. Therefore, the appropriate efficacies of these drugs may be achieved via their oral administration, even in cattle.

  16. 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

  17. Gastrointestinal drug absorption in rats exposed to 60Co γ-radiation

    International Nuclear Information System (INIS)

    Brady, M.E.

    1976-01-01

    Following exposure of the gastrointestinal (GI) tract to ionizing radiation, its structure and function are altered for several days. Such alterations may affect the bioavailability of orally administered drugs. The potential mechanisms by which radiation may affect drug absorption were explored by studying the absorption of four test drugs, sulfanilamide, bretylium, sulfisoxazole acetyl, and riboflavin, in rats that were exposed to 850 R cobalt-60 gamma-radiation or sham irradiated. In one series of experiments, the drugs were administered orally and the amount of drug excreted in urine was used as a measure of the extent of their absorption. Cumulative urinary excretion of the drugs was shown to be a valid measure of absorption since it was not affected by radiation after intravenous administration of the drugs. At one day post-irradiation, the extent of absorption of sulfanilamide and bretylium was not affected by radiation but the absorption of sulfisoxazole acetyl and riboflavin was increased. At five days post-irradiation, there was no detectable difference between irradiated and control animals in the extent of absorption of the drugs. The fraction of sulfanilamide excreted in the urine as 4 N-conjugate was increased at one day post-irradiation. The increased excretion of metabolite appeared to result from metabolism of the drug by gut flora prior to absorption. This study shows that radiation-induced alterations in the absorption of orally administered drugs are due primarily to slowed gastric emptying. In general, slowed gastric emptying causes the rate of drug absorption to decline. The extent of absorption of drugs that are normally well absorbed is not affected by radiation while the extent of absorption of drugs that normally are absorbed poorly may be increased after irradiation of the GI tract

  18. Rapid identification of drugs in the overdosed patient.

    Science.gov (United States)

    Hackett, L P; Dusci, L J

    1977-01-01

    A rapid analytical procedure is described for a variety of drugs that could be present in the overdosed patient. The technique used gives quantitative results for most of the drugs analyzed in serum using gas chromatography and incorporates thin-layer chromatography and spot tests for drug confirmation. The procedure is novel for it relies on the initial extraction of acidics, basics, and neutrals from serum acidified with hydroxhloric acid.

  19. Improved intestinal absorption of a poorly water-soluble oral drug using mannitol microparticles containing a nanosolid drug dispersion.

    Science.gov (United States)

    Nishino, Yukiko; Kubota, Aya; Kanazawa, Takanori; Takashima, Yuuki; Ozeki, Tetsuya; Okada, Hiroaki

    2012-11-01

    A nozzle for a spray dryer that can prepare microparticles of water-soluble carriers containing various nanoparticles in a single step was previously developed in our laboratory. To enhance the solubility and intestinal absorption of poorly water-soluble drugs, we used probucol (PBL) as a poorly water-soluble drug, mannitol (MAN) as a water-soluble carrier for the microparticles, and EUDRAGIT (EUD) as a polymer vehicle for the solid dispersion. PBL-EUD-acetone-methanol and aqueous MAN solutions were simultaneously supplied through different liquid passages of the spray nozzle and dried together. PBL-EUD solid dispersion was nanoprecipitated in the MAN solution using an antisolvent mechanism and rapidly dried by surrounding it with MAN. PBL in the dispersion vehicle was amorphous and had higher physical stability according to powder X-ray diffraction and differential scanning calorimetry analysis. The bioavailability of PBL in PBL-EUD S-100-MAN microparticles after oral administration in rats was markedly higher (14- and 6.2-fold, respectively) than that of the original PBL powder and PBL-MAN microparticles. These results demonstrate that the composite microparticles containing a nanosized solid dispersion of a poorly water-soluble drug prepared using the spray nozzle developed by us should be useful to increase the solubility and bioavailability of drugs after oral administration. Copyright © 2012 Wiley Periodicals, Inc.

  20. Interplay of Drug-Metabolizing Enzymes and Transporters in Drug Absorption and Disposition.

    Science.gov (United States)

    Shi, Shaojun; Li, Yunqiao

    2014-01-01

    In recent years, the functional interplay between drug-metabolizing enzymes (DMEs) and drug transporters (DTs) in drug absorption and disposition, as well as the complex drug interactions (DIs), has become an intriguing contention, which has also been termed the "transport-metabolism interplay". The current mechanistic understanding for this interplay is first discussed. In the present article, studies investigating the interplay between cytochrome P450 enzymes (CYPs) and efflux transporters have been systematically reviewed in vitro, in situ, in silico, in animals and humans, followed by CYPs-uptake transporters, CYPs-uptake transporters-efflux transporters, and phase II metabolic enzymes-transporters interplay studies. Although several cellular, isolated organ and whole animal studies, in conjunction with simulation and modelling, have addressed the issue that DMEs and DTs can work cooperatively to affect the bioavailability of shared substrate drugs, convincing evidences in human studies are still lacking. Furthermore, the functional interplay between DMEs and DTs will be highly substrate- and dose- dependent. Additionally, we review recent studies to evaluate the influence of genetic variations in the interplay between DMEs and DTs, which might be helpful for the prediction of pharmacokinetics (PK) and possible DIs in human more correctly. There is strong evidence of coordinately regulated DEMs and DTs gene expression and protein activity (e.g. nuclear receptors). Taken together, further investigations and analysis are urgently needed to explore the functional interplay of DMEs and DTs and to delineate the underlying mechanisms.

  1. Radiological absorption characteristics of sedatives, hypnotic drugs and psychopharmaceuticals with respect to drug intoxications in suicides

    International Nuclear Information System (INIS)

    Melchert, H.

    1980-01-01

    When in cases of patients with severe intoxication aspiration is suspected clinically, an X-ray image of the thorax is made in order to prevent that atelectases or inflammatory pulmonary infiltrations remain undetected, in addition, an X-ray image of the abdomen should be made in each in which the swallowed preparation has not been identified, because our investigations have proved that any drugs of any kind with an absorption coefficient above 0.23 are radiologically detectable, when the resorption process is not finished yet. In shadow-producing pharmaceuticals these abdominal X-ray images allow not only the examination and supervision of the toxic resorption of an enterally taken preparation, but also the possible identification of the type the drug belongs to. Moreover, information about quantity, resorption, and localisation of the tablets being somewhere in the gastrointestinal tract can be obtained. (orig.) [de

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

    International Nuclear Information System (INIS)

    Grier, C. J.; Brandt, W. N.; Trump, J. R.; Schneider, D. P.; Hall, P. B.; Shen, Yue; Vivek, M.; Dawson, K. S.; Ak, N. Filiz; Chen, Yuguang; Denney, K. D.; Kochanek, C. S.; Peterson, B. M.; Green, Paul J.; Jiang, Linhua; McGreer, Ian D.; Pâris, I.; Tao, Charling; Wood-Vasey, W. M.; Bizyaev, Dmitry

    2015-01-01

    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 −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 e ≳ 3.9 × 10 5 cm −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. 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.

  4. Mapping Quantitatively Regional Drug Absorption in Canines with IntelliCap System

    NARCIS (Netherlands)

    Becker, D.; Schütz, H.; Beyerbach, A.; Zou, H.; Shimizu, J.; Iordanov, V.P.

    2011-01-01

    Quantitative regional absorption of a drug under development was studied by using the novel IntelliCap system. IntelliCap is an orally swallowable programmable drug delivery capsule and capable of real-time monitoring of physiological conditions (pH, temperature), consequently allowing localization

  5. Correlation between oral drug absorption in humans and apparent drug permeability coefficients in human intestinal epithelial (Caco-2) cells

    International Nuclear Information System (INIS)

    Artursson, P.; Karlsson, J.

    1991-01-01

    Monolayers of a well differentiated human intestinal epithelial cell line, Caco-2, were used as a model to study passive drug absorption across the intestinal epithelium. Absorption rate constants (expressed as apparent permeability coefficients) were determined for 20 drugs and peptides with different structural properties. The permeability coefficients ranged from approximately 5 x 10 - 8 to 5 x 10 - 5 cm/s. A good correlation was obtained between data on oral absorption in humans and the results in the Caco-2 model. Drugs that are completely absorbed in humans had permeability coefficients greater than 1 x 10 - 6 cm/s. Drugs that are absorbed to greater than 1% but less than 100% had permeability coefficients of 0.1-1.0 x 10 - 6 cm/s while drugs and peptides that are absorbed to less than 1% had permeability coefficients of less than or equal to 1 x 10 - 7 cm/s. The results indicate that Caco-2 monolayers can be used as a model for studies on intestinal drug absorption

  6. Rapid drug susceptibility test of mycobacterium tuberculosis by bioluminescence sensor

    Science.gov (United States)

    Lu, Bin; Xu, Shunqing; Chen, Zifei; Zhou, Yikai

    2001-09-01

    With the persisting increase of drug-resistant stains of M. Tuberculosis around the world, rapid and sensitive detection of antibiotic of M. Tuberculosis is becoming more and more important. In the present study, drug susceptibility of M. tuberculosis were detected by recombination mycobacteriophage combined with bioluminescence sensor. It is based on the use of recombination mycobacteriophage which can express firefly luciferase when it infects viable mycobacteria, and can effectively produce quantifiable photon. Meanwhile, in mycobacterium cells treated with active antibiotic, no light is observed. The emitted light is recorded by a bioluminscence sensor, so the result of drug-resistant test can be determined by the naked eye. 159 stains of M. tuberculosis were applied to this test on their resistant to rifampin, streptomycin and isoniazid. It is found that the agreement of this assay with Liewenstein- Jensen slat is: rifampin 95.60 percent, isoniazid 91.82 percent, streptomycin 88.68 percent, which showed that it is a fast and practical method to scene and detect drug resistant of mycobacterium stains.

  7. Plasmonic Nanobubbles Rapidly Detect and Destroy Drug-Resistant Tumors

    Science.gov (United States)

    Lukianova-Hleb, Ekaterina Y.; Ren, Xiaoyang; Townley, Debra; Wu, Xiangwei; Kupferman, Michael E.; Lapotko, Dmitri O.

    2012-01-01

    The resistance of residual cancer cells after oncological resection to adjuvant chemoradiotherapies results in both high recurrence rates and high non-specific tissue toxicity, thus preventing the successful treatment of such cancers as head and neck squamous cell carcinoma (HNSCC). The patients' survival rate and quality of life therefore depend upon the efficacy, selectivity and low non-specific toxicity of the adjuvant treatment. We report a novel, theranostic in vivo technology that unites both the acoustic diagnostics and guided intracellular delivery of anti-tumor drug (liposome-encapsulated doxorubicin, Doxil) in one rapid process, namely a pulsed laser-activated plasmonic nanobubble (PNB). HNSCC-bearing mice were treated with gold nanoparticle conjugates, Doxil, and single near-infrared laser pulses of low energy. Tumor-specific clusters of gold nanoparticles (solid gold spheres) converted the optical pulses into localized PNBs. The acoustic signals of the PNB detected the tumor with high specificity and sensitivity. The mechanical impact of the PNB, co-localized with Doxil liposomes, selectively ejected the drug into the cytoplasm of cancer cells. Cancer cell-specific generation of PNBs and their intracellular co-localization with Doxil improved the in vivo therapeutic efficacy from 5-7% for administration of only Doxil or PNBs alone to 90% thus demonstrating the synergistic therapeutic effect of the PNB-based intracellular drug release. This mechanism also reduced the non-specific toxicity of Doxil below a detectable level and the treatment time to less than one minute. Thus PNBs combine highly sensitive diagnosis, overcome drug resistance and minimize non-specific toxicity in a single rapid theranostic procedure for intra-operative treatment. PMID:23139725

  8. Terahertz absorption spectra of commonly used antimalarial drugs

    Science.gov (United States)

    Bawuah, Prince; Zeitler, J. Axel; Ketolainen, Jarkko; Peiponen, Kai-Erik

    2018-03-01

    Terahertz (THz) spectra from the pure forms [i.e. the active pharmaceutical ingredients (APIs)] of four commonly used antimalarial drugs are reported. The well-defined spectral fingerprints obtained for these APIs in the spectral range of 0.1 THz-3 THz show the sensitivity of the THz time-domain spectroscopic (THz-TDS) method for screening antimalarial drugs. For identification purpose, two commercially available antimalarial tablets were detected. Clear spectral fingerprints of the APIs in the antimalarial tablets were obtained even amidst the several types of excipients present in the tablets. This observation further proves the high sensitivity of the THz techniques in tracking the presence or absence of API in a pharmaceutical tablet. We envisage that the spectral data obtained for these drugs can contribute to a spectroscopic database in the far infrared spectral region and hence support the modelling of THz sensing to differentiate between genuine and counterfeit antimalarial tablets.

  9. Terahertz absorption spectra of commonly used antimalarial drugs

    Science.gov (United States)

    Bawuah, Prince; Zeitler, J. Axel; Ketolainen, Jarkko; Peiponen, Kai-Erik

    2018-06-01

    Terahertz (THz) spectra from the pure forms [i.e. the active pharmaceutical ingredients (APIs)] of four commonly used antimalarial drugs are reported. The well-defined spectral fingerprints obtained for these APIs in the spectral range of 0.1 THz-3 THz show the sensitivity of the THz time-domain spectroscopic (THz-TDS) method for screening antimalarial drugs. For identification purpose, two commercially available antimalarial tablets were detected. Clear spectral fingerprints of the APIs in the antimalarial tablets were obtained even amidst the several types of excipients present in the tablets. This observation further proves the high sensitivity of the THz techniques in tracking the presence or absence of API in a pharmaceutical tablet. We envisage that the spectral data obtained for these drugs can contribute to a spectroscopic database in the far infrared spectral region and hence support the modelling of THz sensing to differentiate between genuine and counterfeit antimalarial tablets.

  10. 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.

  11. New Insights into Drug Absorption from Oil Depots

    NARCIS (Netherlands)

    Kalicharan, R.W.

    2017-01-01

    Sustained delivery formulations are used in order to prolong the pharmacological activity of a drug. A commonly used parenteral sustained delivery formulation is an oil depot which consists of a solution of lipophilic molecules in a vegetable oil. These are normally administered either

  12. 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......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...... and state-of-the art methodologies to study API properties impacting on oral absorption are reviewed. Assays performed during early development, i.e. physicochemical characterization, dissolution profiles under physiological conditions, permeability assays and the impact of excipients on these properties...

  13. Active intestinal drug absorption and the solubility-permeability interplay.

    Science.gov (United States)

    Porat, Daniel; Dahan, Arik

    2018-02-15

    The solubility-permeability interplay deals with the question: what is the concomitant effect on the drug's apparent permeability when increasing the apparent solubility with a solubility-enabling formulation? The solubility and the permeability are closely related, exhibit certain interplay between them, and ongoing research throughout the past decade shows that treating the one irrespectively of the other may be insufficient. The aim of this article is to provide an overview of the current knowledge on the solubility-permeability interplay when using solubility-enabling formulations for oral lipophilic drugs, highlighting active permeability aspects. A solubility-enabling formulation may affect the permeability in opposite directions; the passive permeability may decrease as a result of the apparent solubility increase, according to the solubility-permeability tradeoff, but at the same time, certain components of the formulation may inhibit/saturate efflux transporters (when relevant), resulting in significant apparent permeability increase. In these cases, excipients with both solubilizing and e.g. P-gp inhibitory properties may lead to concomitant increase of both the solubility and the permeability. Intelligent development of such formulation will account for the simultaneous effects of the excipients' nature/concentrations on the two arms composing the overall permeability: the passive and the active arms. Overall, thorough mechanistic understanding of the various factors involved in the solubility-permeability interplay may allow developing better solubility-enabling formulations, thereby exploiting the advantages analyzed in this article, offering oral delivery solution even for BCS class IV drugs. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Ethanol-drug absorption interaction: potential for a significant effect on the plasma pharmacokinetics of ethanol vulnerable formulations.

    Science.gov (United States)

    Lennernäs, Hans

    2009-01-01

    Generally, gastric emptying of a drug to the small intestine is controlled by gastric motor activity and is the main factor affecting the onset of absorption. Accordingly, the emptying rate from the stomach is mainly affected by the digestive state, the properties of the pharmaceutical formulation and the effect of drugs, posture and circadian rhythm. Variability in the gastric emptying of drugs is reflected in variability in the absorption rate and the shape of the plasma pharmacokinetic profile. When ethanol interacts with an oral controlled release product, such that the mechanism controlling drug release is impaired, the delivery of the dissolved dose into the small intestine and the consequent absorption may result in dangerously high plasma concentrations. For example, the maximal plasma concentration of hydromorphone has individually been shown to be increased as much as 16 times through in vivo testing as a result of this specific pharmacokinetic ethanol-drug formulation interaction. Thus, a pharmacokinetic ethanol-drug interaction is a very serious safety concern when substantially the entire dose from a controlled release product is rapidly emptied into the small intestine (dose dumping), having been largely dissolved in a strong alcoholic beverage in the stomach during a sufficient lag-time in gastric emptying. Based on the literature, a two hour time frame for screening the in vitro dissolution profile of a controlled release product in ethanol concentrations of up to 40% is strongly supported and may be considered as the absolute minimum standard. It is also evident that the dilution, absorption and metabolism of ethanol in the stomach are processes with a minor effect on the local ethanol concentration and that ethanol exposure will be highly dependent on the volume and ethanol concentration of the fluid ingested, together with the rate of intake and gastric emptying. When and in which patients a clinically significant dose dumping will happen is

  15. 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...

  16. The coupling of rapidly synergistic cloud point extraction with thermospray flame furnace atomic absorption spectrometry

    International Nuclear Information System (INIS)

    Wen, X.; Deng, Q.; Guo, J.; Zhao, X.; Zhao, Y.; Ji, S.

    2012-01-01

    Rapidly synergistic cloud point extraction (RS-CPE) was coupled with thermospray flame furnace atomic absorption spectrometry (TS-FF-AAS) to result in new CPE patterns and accelerated (1 min) protocols. It is demonstrated, for the case of copper (II) ion, that TS-FF-AAS improves the sampling efficiency and the sensitivity of FAAS determinations. Problems of nebulization associated with previous methods based on the coupling of FAAS and RS-CPE are overcome. TS-FF-AAS also improves sensitivity and gives a limit of detection for copper of 0.20 μg L -1 , which is better by a factor of 32. Compared to direct FAAS, the factor is 114. (author)

  17. Hydrodynamic Impacts on Dissolution, Transport and Absorption from Thousands of Drug Particles Moving within the Intestines

    Science.gov (United States)

    Behafarid, Farhad; Brasseur, James G.

    2017-11-01

    Following tablet disintegration, clouds of drug particles 5-200 μm in diameter pass through the intestines where drug molecules are absorbed into the blood. Release rate depends on particle size, drug solubility, local drug concentration and the hydrodynamic environment driven by patterned gut contractions. To analyze the dynamics underlying drug release and absorption, we use a 3D lattice Boltzmann model of the velocity and concentration fields driven by peristaltic contractions in vivo, combined with a mathematical model of dissolution-rate from each drug particle transported through the grid. The model is empirically extended for hydrodynamic enhancements to release rate by local convection and shear-rate, and incorporates heterogeneity in bulk concentration. Drug dosage and solubility are systematically varied along with peristaltic wave speed and volume. We predict large hydrodynamic enhancements (35-65%) from local shear-rate with minimal enhancement from convection. With high permeability boundary conditions, a quasi-equilibrium balance between release and absorption is established with volume and wave-speed dependent transport time scale, after an initial transient and before a final period of dissolution/absorption. Supported by FDA.

  18. 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

  19. A rapidly-reversible absorptive and emissive vapochromic Pt(II) pincer-based chemical sensor.

    Science.gov (United States)

    Bryant, M J; Skelton, J M; Hatcher, L E; Stubbs, C; Madrid, E; Pallipurath, A R; Thomas, L H; Woodall, C H; Christensen, J; Fuertes, S; Robinson, T P; Beavers, C M; Teat, S J; Warren, M R; Pradaux-Caggiano, F; Walsh, A; Marken, F; Carbery, D R; Parker, S C; McKeown, N B; Malpass-Evans, R; Carta, M; Raithby, P R

    2017-11-27

    Selective, robust and cost-effective chemical sensors for detecting small volatile-organic compounds (VOCs) have widespread applications in industry, healthcare and environmental monitoring. Here we design a Pt(II) pincer-type material with selective absorptive and emissive responses to methanol and water. The yellow anhydrous form converts reversibly on a subsecond timescale to a red hydrate in the presence of parts-per-thousand levels of atmospheric water vapour. Exposure to methanol induces a similarly-rapid and reversible colour change to a blue methanol solvate. Stable smart coatings on glass demonstrate robust switching over 10 4 cycles, and flexible microporous polymer membranes incorporating microcrystals of the complex show identical vapochromic behaviour. The rapid vapochromic response can be rationalised from the crystal structure, and in combination with quantum-chemical modelling, we provide a complete microscopic picture of the switching mechanism. We discuss how this multiscale design approach can be used to obtain new compounds with tailored VOC selectivity and spectral responses.

  20. 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.

  1. An analytical solution for percutaneous drug absorption: application and removal of the vehicle.

    Science.gov (United States)

    Simon, L; Loney, N W

    2005-10-01

    The methods of Laplace transform were used to solve a mathematical model developed for percutaneous drug absorption. This model includes application and removal of the vehicle from the skin. A system of two linear partial differential equations was solved for the application period. The concentration of the medicinal agent in the skin at the end of the application period was used as the initial condition to determine the distribution of the drug in the skin following instantaneous removal of the vehicle. The influences of the diffusion and partition coefficients, clearance factor and vehicle layer thickness on the amount of drug in the vehicle and the skin were discussed.

  2. Computational Studies of Drug Release, Transport and Absorption in the Human Intestines

    Science.gov (United States)

    Behafarid, Farhad; Brasseur, J. G.; Vijayakumar, G.; Jayaraman, B.; Wang, Y.

    2016-11-01

    Following disintegration of a drug tablet, a cloud of particles 10-200 μm in diameter enters the small intestine where drug molecules are absorbed into the blood. Drug release rate depends on particle size, solubility and hydrodynamic enhancements driven by gut motility. To quantify the interrelationships among dissolution, transport and wall permeability, we apply lattice Boltzmann method to simulate the drug concentration field in the 3D gut released from polydisperse distributions of drug particles in the "fasting" vs. "fed" motility states. Generalized boundary conditions allow for both solubility and gut wall permeability to be systematically varied. We apply a local 'quasi-steady state' approximation for drug dissolution using a mathematical model generalized for hydrodynamic enhancements and heterogeneity in drug release rate. We observe fundamental differences resulting from the interplay among release, transport and absorption in relationship to particle size distribution, luminal volume, motility, solubility and permeability. For example, whereas smaller volume encourages higher bulk concentrations and reduced release rate, it also encourages higher absorption rate, making it difficult to generalize predictions. Supported by FDA.

  3. 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.

  4. High-speed combustion diagnostics in a rapid compression machine by broadband supercontinuum absorption spectroscopy.

    Science.gov (United States)

    Werblinski, Thomas; Fendt, Peter; Zigan, Lars; Will, Stefan

    2017-05-20

    The first results under fired internal combustion engine conditions based on a supercontinuum absorption spectrometer are presented and discussed. Temperature, pressure, and water mole fraction are inferred simultaneously from broadband H 2 O absorbance spectra ranging from 1340 nm to 1440 nm. The auto-ignition combustion process is monitored for two premixed n-heptane/air mixtures with 10 kHz in a rapid compression machine. Pressure and temperature levels during combustion exceed 65 bar and 1900 K, respectively. To allow for combustion measurements, the robustness of the spectrometer against beam steering has been improved compared to its previous version. Additionally, the detectable wavelength range has been extended further into the infrared region to allow for the acquisition of distinct high-temperature water transitions located in the P-branch above 1410 nm. Based on a theoretical study, line-of-sight (LOS) effects introduced by temperature stratification on the broadband fitting algorithm in the complete range from 1340 nm to 1440 nm are discussed. In this context, the recorded spectra during combustion were evaluated only within a narrower spectral region exhibiting almost no interference from low-temperature molecules (here, P-branch from 1410 nm to 1440 nm). It is shown that this strategy mitigates almost all of the LOS effects introduced by cold molecules and the evaluation of the spectrum in the entirely recorded wavelength range at engine combustion conditions.

  5. Automation of cell-based drug absorption assays in 96-well format using permeable support systems.

    Science.gov (United States)

    Larson, Brad; Banks, Peter; Sherman, Hilary; Rothenberg, Mark

    2012-06-01

    Cell-based drug absorption assays, such as Caco-2 and MDCK-MDR1, are an essential component of lead compound ADME/Tox testing. The permeability and transport data they provide can determine whether a compound continues in the drug discovery process. Current methods typically incorporate 24-well microplates and are performed manually. Yet the need to generate absorption data earlier in the drug discovery process, on an increasing number of compounds, is driving the use of higher density plates. A simple, more efficient process that incorporates 96-well permeable supports and proper instrumentation in an automated process provides more reproducible data compared to manual methods. Here we demonstrate the ability to perform drug permeability and transport assays using Caco-2 or MDCKII-MDR1 cells. The assay procedure was automated in a 96-well format, including cell seeding, media and buffer exchanges, compound dispense, and sample removal using simple robotic instrumentation. Cell monolayer integrity was confirmed via transepithelial electrical resistance and Lucifer yellow measurements. Proper cell function was validated by analyzing apical-to-basolateral and basolateral-to-apical movement of rhodamine 123, a known P-glycoprotein substrate. Apparent permeability and efflux data demonstrate how the automated procedure provides a less variable method than manual processing, and delivers a more accurate assessment of a compound's absorption characteristics.

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

    KAUST Repository

    Nasir, Ehson Fawad; Farooq, Aamir

    2016-01-01

    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

  7. Intra-pulse laser absorption sensor with cavity enhancement for oxidation experiments in a rapid compression machine

    KAUST Repository

    Nasir, Ehson Fawad; Farooq, Aamir

    2018-01-01

    A sensor based on a mid-IR pulsed quantum cascade laser (QCL) and off-axis cavity enhanced absorption spectroscopy (OA-CEAS) has been developed for highly sensitive concentration measurements of carbon monoxide (CO) in a rapid compression machine

  8. Circumvention of the tumor membrane barrier to WR-2721 absorption by reduction of drug hydrophilicity

    International Nuclear Information System (INIS)

    Yuhas, J.M.; Davis, M.E.; Glover, D.; Brown, D.Q.; Ritter, M.

    1982-01-01

    In attempting to account for the ability of most solid tumors to restrict the absorption of WR-2721, aminopropyl-aminoethylphosphorothioate, we examined a number of drug characteristics which might allow for this restriction, and observed that drug hypdrophilicity was a major contributing factor. When the highly hydrophilic WR-2721 was dephosphorylated, the drug became less hydrophilic and could readily cross tumor cell membranes. In addition, conventional radioprotectants, such as cysteine and mercaptoethylamine, were shown to be less hydrophilic than WR-2721 and also to cross tumor membranes readily. Therefore, drug hydrophilicity would appear to be the factor underlying the ability of WR-2721 to selectively protect normal tissues while most other protectors alter the radiation resistance of normal and tumor tissue alike. A red blood cell model for studying this problem in greater detail is described

  9. Rapidly reconfigurable slow-light system based on off-resonant Raman absorption

    International Nuclear Information System (INIS)

    Vudyasetu, Praveen K.; Howell, John C.; Camacho, Ryan M.

    2010-01-01

    We present a slow-light system based on dual Raman absorption resonances in warm rubidium vapor. Each Raman absorption resonance is produced by a control beam in an off-resonant Λ system. This system combines all optical control of the Raman absorption and the low-dispersion broadening properties of the double Lorentzian absorption slow light. The bandwidth, group delay, and central frequency of the slow-light system can all be tuned dynamically by changing the properties of the control beam. We demonstrate multiple pulse delays with low distortion and show that such a system has fast switching dynamics and thus fast reconfiguration rates.

  10. Application of ion mobility spectrometer for rapid drug detection

    Energy Technology Data Exchange (ETDEWEB)

    Xuemei, Zhu; Jian, Zheng [The Third Research Inst. of Ministry of Public Security, Shanghai (China); Yongjie, Lv; Yangqin, Chen [Department of Physics, Key Laboratory of Optical and Magnetic Resonance Spectroscopy, East China Normal Univ., Shanghai (China)

    2007-10-15

    A {sup 63}Ni source-based high resolution ion mobility spectrometer (IMS) was developed and applied to drug detection. The drugs included opium, morphine, heroin, methamphetamine, MDMA, MDEA, ketamine and cannabis. Their ion mobility spectra were acquired, ion types were derived and reduced mobilities were calculated, which are in good agreement with the data reported in literatures. The results indicate that the IMS can detect effectively a variety of drugs, especially for the amphetamine derivatives. And the reduced mobility standard database of drugs was established. (authors)

  11. Application of ion mobility spectrometer for rapid drug detection

    International Nuclear Information System (INIS)

    Zhu Xuemei; Zheng Jian; Lv Yongjie; Chen Yangqin

    2007-01-01

    A 63 Ni source-based high resolution ion mobility spectrometer (IMS) was developed and applied to drug detection. The drugs included opium, morphine, heroin, methamphetamine, MDMA, MDEA, ketamine and cannabis. Their ion mobility spectra were acquired, ion types were derived and reduced mobilities were calculated, which are in good agreement with the data reported in literatures. The results indicate that the IMS can detect effectively a variety of drugs, especially for the amphetamine derivatives. And the reduced mobility standard database of drugs was established. (authors)

  12. Multi-purposable filaments of HPMC for 3D printing of medications with tailored drug release and timed-absorption.

    Science.gov (United States)

    Kadry, Hossam; Al-Hilal, Taslim A; Keshavarz, Ali; Alam, Farzana; Xu, Changxue; Joy, Abraham; Ahsan, Fakhrul

    2018-04-20

    Three-dimensional printing (3DP), though developed for nonmedical applications and once regarded as futuristic only, has recently been deployed for the fabrication of pharmaceutical products. However, the existing feeding materials (inks and filaments) that are used for printing drug products have various shortcomings, including the lack of biocompatibility, inadequate extrudability and printability, poor drug loading, and instability. Here, we have sought to develop a filament using a single pharmaceutical polymer, with no additives, which can be multi-purposed and manipulated by computational design for the preparation of tablets with desired release and absorption patterns. As such, we have used hydroxypropyl-methylcellulose (HPMC) and diltiazem, a model drug, to prepare both drug-free and drug-impregnated filaments, and investigated their thermal and crystalline properties, studied the cytotoxicity of the filaments, designed and printed tablets with various infill densities and patterns. By alternating the drug-free and drug-impregnated filaments, we fabricated various types of tablets, studied the drug release profiles, and assessed oral absorption in rats. Both diltiazem and HPMC were stable at extrusion and printing temperatures, and the drug loading was 10% (w/w). The infill density, as well as infill patterns, influenced the drug release profile, and thus, when the infill density was increased to 100%, the percentage of drug released dramatically declined. Tablets with alternating drug-free and drug-loaded layers showed delayed and intermittent drug release, depending on when the drug-loaded layers encountered the dissolution media. Importantly, the oral absorption patterns accurately reproduced the drug release profiles and showed immediate, extended, delayed and episodic absorption of the drug from the rat gastrointestinal tract (GIT). Overall, we have demonstrated here that filaments for 3D printers can be prepared from a pharmaceutical polymer with no

  13. Absorption-desorption of drugs in porous polymers obtained by plasma

    International Nuclear Information System (INIS)

    Gonzalez T, M.

    2016-01-01

    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. A reaction limited in vivo dissolution model for the study of drug absorption: Towards a new paradigm for the biopharmaceutic classification of drugs.

    Science.gov (United States)

    Macheras, Panos; Iliadis, Athanassios; Melagraki, Georgia

    2018-05-30

    The aim of this work is to develop a gastrointestinal (GI) drug absorption model based on a reaction limited model of dissolution and consider its impact on the biopharmaceutic classification of drugs. Estimates for the fraction of dose absorbed as a function of dose, solubility, reaction/dissolution rate constant and the stoichiometry of drug-GI fluids reaction/dissolution were derived by numerical solution of the model equations. The undissolved drug dose and the reaction/dissolution rate constant drive the dissolution rate and determine the extent of absorption when high-constant drug permeability throughout the gastrointestinal tract is assumed. Dose is an important element of drug-GI fluids reaction/dissolution while solubility exclusively acts as an upper limit for drug concentrations in the lumen. The 3D plots of fraction of dose absorbed as a function of dose and reaction/dissolution rate constant for highly soluble and low soluble drugs for different "stoichiometries" (0.7, 1.0, 2.0) of the drug-reaction/dissolution with the GI fluids revealed that high extent of absorption was found assuming high drug- reaction/dissolution rate constant and high drug solubility. The model equations were used to simulate in vivo supersaturation and precipitation phenomena. The model developed provides the theoretical basis for the interpretation of the extent of drug's absorption on the basis of the parameters associated with the drug-GI fluids reaction/dissolution. A new paradigm emerges for the biopharmaceutic classification of drugs, namely, a model independent biopharmaceutic classification scheme of four drug categories based on either the fulfillment or not of the current dissolution criteria and the high or low % drug metabolism. Copyright © 2018. Published by Elsevier B.V.

  15. Rapid interferometric imaging of printed drug laden multilayer structures

    DEFF Research Database (Denmark)

    Sandler, Niklas; Kassamakov, Ivan; Ehlers, Henrik

    2014-01-01

    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...

  16. 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.

  17. Drugs' rapid payoffs distort evaluation of their instrumental uses.

    Science.gov (United States)

    Ainslie, George

    2011-12-01

    Science has needed a dispassionate valuation of psychoactive drugs, but a motivational analysis should be conducted with respect to long-term reward rather than reproductive fitness. Because of hyperbolic overvaluation of short-term rewards, an individual's valuation depends on the time she forms it and the times she will revisit it, sometimes making her best long-term interest lie in total abstinence.

  18. 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...

  19. 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.

  20. Analysis of Intra- and Intersubject Variability in Oral Drug Absorption in Human Bioequivalence Studies of 113 Generic Products.

    Science.gov (United States)

    Sugihara, Masahisa; Takeuchi, Susumu; Sugita, Masaru; Higaki, Kazutaka; Kataoka, Makoto; Yamashita, Shinji

    2015-12-07

    In this study, the data of 113 human bioequivalence (BE) studies of immediate release (IR) formulations of 74 active pharmaceutical ingredients (APIs) conducted at Sawai Pharmaceutical Co., Ltd., was analyzed to understand the factors affecting intra- and intersubject variabilities in oral drug absorption. The ANOVA CV (%) calculated from area under the time-concentration curve (AUC) in each BE study was used as an index of intrasubject variability (Vintra), and the relative standard deviation (%) in AUC was used as that of intersubject variability (Vinter). Although no significant correlation was observed between Vintra and Vinter of all drugs, Vintra of class 3 drugs was found to increase in association with a decrease in drug permeability (P(eff)). Since the absorption of class 3 drugs was rate-limited by the permeability, it was suggested that, for such drugs, the low P(eff) might be a risk factor to cause a large intrasubject variability. To consider the impact of poor water solubility on the variability in BE study, a parameter of P(eff)/Do (Do; dose number) was defined to discriminate the solubility-limited and dissolution-rate-limited absorption of class 2 drugs. It was found that the class 2 drugs with a solubility-limited absorption (P(eff)/Do high intrasubject variability. Furthermore, as a reason for high intra- or intersubject variability in AUC for class 1 drugs, effects of drug metabolizing enzymes were investigated. It was demonstrated that intrasubject variability was high for drugs metabolized by CYP3A4 while intersubject variability was high for drugs metabolized by CYP2D6. For CYP3A4 substrate drugs, the Km value showed the significant relation with Vintra, indicating that the affinity to the enzyme can be a parameter to predict the risk of high intrasubject variability. In conclusion, by analyzing the in house data of human BE study, low permeability, solubility-limited absorption, and high affinity to CYP3A4 are identified as risk factors for

  1. Rapid detection of drug metabolites in latent fingermarks.

    Science.gov (United States)

    Hazarika, Pompi; Jickells, Sue M; Russell, David A

    2009-01-01

    Magnetic particles functionalised with anti-cotinine antibody have been used to image latent fingermarks through the detection of the cotinine antigen in the sweat deposited within the fingerprints of smokers. The antibody-magnetic particle conjugates are readily applied to latent fingerprints while excess reagents are removed through the use of a magnetic wand. The results have shown that drug metabolites, such as cotinine, can be detected and used to image the fingermark to establish the identity of an individual within 15 minutes.

  2. Imperfect drug penetration leads to spatial monotherapy and rapid evolution of multidrug resistance

    NARCIS (Netherlands)

    Moreno-Gamez, Stefany; Hill, Alison L.; Rosenbloom, Daniel I. S.; Petrov, Dmitri A.; Nowak, Martin A.; Pennings, Pleuni S.

    2015-01-01

    Infections with rapidly evolving pathogens are often treated using combinations of drugs with different mechanisms of action. One of the major goal of combination therapy is to reduce the risk of drug resistance emerging during a patient's treatment. Although this strategy generally has significant

  3. In Vitro Characterization of the Biomimetic Properties of Poly(dimethylsiloxane) To Simulate Oral Drug Absorption.

    Science.gov (United States)

    Sinko, Patrick D; Gidley, David; Vallery, Richard; Lamoureux, Aaron; Amidon, Gordon L; Amidon, Gregory E

    2017-12-04

    The potential use of poly(dimethylsiloxane) (PDMS) as an in vitro biomimetic analogue of the passive drug absorption process in the human gastrointestinal tract (GI) is assessed. PDMS is biomimetic because of similarities in small molecule transport, such as mechanism, ionization selectivity, lipophilicity. Nine molecular probes are used to evaluate the transport pathways and properties used to predict human oral absorption rates. The transport pathways through PDMS (bulk/pore) are analogous to transcellular (TCDT) and paracellular (PCDT) drug transport pathways. PDMS PCDT is assessed using positronium annihilation lifetime spectroscopy (PALS) and partition experiments; TCDT using diffusion and partition experiments. PALS determined that PDMS pores were uniform (D ∼ 0.85 nm), isolated, and void volume was unaffected by drug accumulation after equilibrium partitioning. Therefore, there is no PCDT or convective flow through PDMS. A strong linear correlation exists between predicted octanol-water partition coefficients and PDMS partition coefficients (LogK PDMS = 0.736 × LogP O-W - 0.971, R 2 = 0.981). The pH-partition hypothesis is confirmed in PDMS using ibuprofen over pH 2-12. Diffusivity through PDMS is a function of lipophilicity and polar surface area K × D PDMS = 4.46 × 10 -8 × e 2.91×LogK PDMS (R 2 = 0.963) and [Formula: see text] (R 2 = 0.973). Varying the mass% of curing agent changed the lipophilicity and diffusivity (p < 0.02), but not practically (K × D = 2.23 × 10 -5 cm 2 s -1 vs 2.60 × 10 -5 cm 2 s -1 ), and does affect elastic modulus (3.2% = 0.3 MPa to 25% = 3.2 MPa).

  4. Evaluation of rapid radiometric method for drug susceptibility testing of Mycobacterium tuberculosis

    International Nuclear Information System (INIS)

    Siddiqi, S.H.; Libonati, J.P.; Middlebrook, G.

    1981-01-01

    A total of 106 isolates of Mycobacterium tuberculosis were tested for drug susceptibility by the conventional 7H11 plate method and by a new rapid radiometric method using special 7H12 liquid medium with 14 C-labeled substrate. Results obtained by the two methods were compared for rapidity, sensitivity, and specificity of the new test method. There was 98% overall agreement between the results obtained by the two methods. Of a total of 424 drug tests, only 8 drug results did not agree, mostly in the case of streptomycin. This new procedure was found to be rapid, with 87% of the tests results reportable within 4 days and 98% reportable within 5 days as compared to the usual 3 weeks required with the conventional indirect susceptibility test method. The results of this preliminary study indicate that the rapid radiometric method seems to have the potential for routine laboratory use and merits further investigations

  5. In Vitro-In Vivo Predictive Dissolution-Permeation-Absorption Dynamics of Highly Permeable Drug Extended-Release Tablets via Drug Dissolution/Absorption Simulating System and pH Alteration.

    Science.gov (United States)

    Li, Zi-Qiang; Tian, Shuang; Gu, Hui; Wu, Zeng-Guang; Nyagblordzro, Makafui; Feng, Guo; He, Xin

    2018-05-01

    Each of dissolution and permeation may be a rate-limiting factor in the absorption of oral drug delivery. But the current dissolution test rarely took into consideration of the permeation property. Drug dissolution/absorption simulating system (DDASS) valuably gave an insight into the combination of drug dissolution and permeation processes happening in human gastrointestinal tract. The simulated gastric/intestinal fluid of DDASS was improved in this study to realize the influence of dynamic pH change on the complete oral dosage form. To assess the effectiveness of DDASS, six high-permeability drugs were chosen as model drugs, including theophylline (pK a1  = 3.50, pK a2  = 8.60), diclofenac (pK a  = 4.15), isosorbide 5-mononitrate (pK a  = 7.00), sinomenine (pK a  = 7.98), alfuzosin (pK a  = 8.13), and metoprolol (pK a  = 9.70). A general elution and permeation relationship of their commercially available extended-release tablets was assessed as well as the relationship between the cumulative permeation and the apparent permeability. The correlations between DDASS elution and USP apparatus 2 (USP2) dissolution and also between DDASS permeation and beagle dog absorption were developed to estimate the predictability of DDASS. As a result, the common elution-dissolution relationship was established regardless of some variance in the characteristic behavior between DDASS and USP2 for drugs dependent on the pH for dissolution. Level A in vitro-in vivo correlation between DDASS permeation and dog absorption was developed for drugs with different pKa. The improved DDASS will be a promising tool to provide a screening method on the predictive dissolution-permeation-absorption dynamics of solid drug dosage forms in the early-phase formulation development.

  6. 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.

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

    Science.gov (United States)

    Imashuku, Yasuhiko; Kitagawa, Hirotoshi; Mizuno, Takayoshi; Fukushima, Yutaka

    2017-01-01

    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. PMID:28217070

  8. Rapid Optimization of External Quantum Efficiency of Thin Film Solar Cells Using Surrogate Modeling of Absorptivity.

    Science.gov (United States)

    Kaya, Mine; Hajimirza, Shima

    2018-05-25

    This paper uses surrogate modeling for very fast design of thin film solar cells with improved solar-to-electricity conversion efficiency. We demonstrate that the wavelength-specific optical absorptivity of a thin film multi-layered amorphous-silicon-based solar cell can be modeled accurately with Neural Networks and can be efficiently approximated as a function of cell geometry and wavelength. Consequently, the external quantum efficiency can be computed by averaging surrogate absorption and carrier recombination contributions over the entire irradiance spectrum in an efficient way. Using this framework, we optimize a multi-layer structure consisting of ITO front coating, metallic back-reflector and oxide layers for achieving maximum efficiency. Our required computation time for an entire model fitting and optimization is 5 to 20 times less than the best previous optimization results based on direct Finite Difference Time Domain (FDTD) simulations, therefore proving the value of surrogate modeling. The resulting optimization solution suggests at least 50% improvement in the external quantum efficiency compared to bare silicon, and 25% improvement compared to a random design.

  9. Development of a Unified Dissolution and Precipitation Model and Its Use for the Prediction of Oral Drug Absorption.

    Science.gov (United States)

    Jakubiak, Paulina; Wagner, Björn; Grimm, Hans Peter; Petrig-Schaffland, Jeannine; Schuler, Franz; Alvarez-Sánchez, Rubén

    2016-02-01

    Drug absorption is a complex process involving dissolution and precipitation, along with other kinetic processes. The purpose of this work was to (1) establish an in vitro methodology to study dissolution and precipitation in early stages of drug development where low compound consumption and high throughput are necessary, (2) develop a mathematical model for a mechanistic explanation of generated in vitro dissolution and precipitation data, and (3) extrapolate in vitro data to in vivo situations using physiologically based models to predict oral drug absorption. Small-scale pH-shift studies were performed in biorelevant media to monitor the precipitation of a set of poorly soluble weak bases. After developing a dissolution-precipitation model from this data, it was integrated into a simplified, physiologically based absorption model to predict clinical pharmacokinetic profiles. The model helped explain the consequences of supersaturation behavior of compounds. The predicted human pharmacokinetic profiles closely aligned with the observed clinical data. In summary, we describe a novel approach combining experimental dissolution/precipitation methodology with a mechanistic model for the prediction of human drug absorption kinetics. The approach unifies the dissolution and precipitation theories and enables accurate predictions of in vivo oral absorption by means of physiologically based modeling.

  10. Rapid Quantification of Energy Absorption and Dissipation Metrics for PPE Padding Materials

    Science.gov (United States)

    2010-01-22

    dampers ,   i.e.,  Hooke’s  Law  springs  and   viscous ...absorbing/dissipating materials. Input forces caused by blast pressures, determined from computational fluid dynamics (CFD) analysis and simulation...simple  lumped-­‐ parameter  elements   –  spring,  k  (energy  storage)   –  damper ,  b  (energy  dissipa/on   Rapid

  11. Observation of reversible, rapid changes in drug susceptibility of hypoxic tumor cells in a microfluidic device

    Energy Technology Data Exchange (ETDEWEB)

    Germain, Todd; Ansari, Megan; Pappas, Dimitri, E-mail: d.pappas@ttu.edu

    2016-09-14

    Hypoxia is a major stimulus for increased drug resistance and for survival of tumor cells. Work from our group and others has shown that hypoxia increases resistance to anti-cancer compounds, radiation, and other damage-pathway cytotoxic agents. In this work we utilize a microfluidic culture system capable of rapid switching of local oxygen concentrations to determine changes in drug resistance in prostate cancer cells. We observed rapid adaptation to hypoxia, with drug resistance to 2 μM staurosporine established within 30 min of hypoxia. Annexin-V/Sytox Green apoptosis assays over 9 h showed 78.0% viability, compared to 84.5% viability in control cells (normoxic cells with no staurosporine). Normoxic cells exposed to the same staurosporine concentration had a viability of 48.6% after 9 h. Hypoxia adaptation was rapid and reversible, with Hypoxic cells treated with 20% oxygen for 30 min responding to staurosporine with 51.6% viability after drug treatment for 9 h. Induction of apoptosis through the receptor-mediated pathway, which bypasses anti-apoptosis mechanisms induced by hypoxia, resulted in 39.4 ± 7% cell viability. The rapid reversibility indicates co-treatment of oxygen with anti-cancer compounds may be a potential therapeutic target. - Highlights: • Microfluidic system switches rapidly between normoxia and hypoxia (5 min). • Observation of rapid adaptation of PC3 cells to hypoxia and normoxia (30 min). • Drug susceptibility in tumor cells restored after chip switched to normoxia for 30 min.

  12. A modified physiological BCS for prediction of intestinal absorption in drug discovery.

    Science.gov (United States)

    Zaki, Noha M; Artursson, Per; Bergström, Christel A S

    2010-10-04

    In this study, the influence of physiologically relevant media on the compound position in a biopharmaceutical classification system (BCS) which resembled the intestinal absorption was investigated. Both solubility and permeability limited compounds (n = 22) were included to analyze the importance of each of these on the final absorption. Solubility was determined in three different dissolution media, phosphate buffer pH 6.5 (PhB 6.5), fasted state simulated intestinal fluid (FaSSIF), and fed state simulated intestinal fluid (FeSSIF) at 37 °C, and permeability values were determined using the 2/4/A1 cell line. The solubility data and membrane permeability values were used for sorting the compounds into a BCS modified to reflect the fasted and fed state. Three of the seven compounds sorted as BCS II in PhB 6.5 (high permeability, low solubility) changed their position to BCS I when dissolved in FaSSIF and/or FeSSIF (high permeability, high solubility). These were low dosed (20 mg or less) lipophilic molecules displaying solvation limited solubility. In contrast, compounds having solid-state limited solubility had a minor increase in solubility when dissolved in FaSSIF and/or FeSSIF. Although further studies are needed to enable general cutoff values, our study indicates that low dosed BCS Class II compounds which have solubility normally restricted by poor solvation may behave as BCS Class I compounds in vivo. The large series of compounds investigated herein reveals the importance of investigating solubility and dissolution under physiologically relevant conditions in all stages of the drug discovery process to push suitable compounds forward, to select proper formulations, and to reduce the risk of food effects.

  13. Intra-pulse laser absorption sensor with cavity enhancement for oxidation experiments in a rapid compression machine

    KAUST Repository

    Nasir, Ehson Fawad

    2018-05-23

    A sensor based on a mid-IR pulsed quantum cascade laser (QCL) and off-axis cavity enhanced absorption spectroscopy (OA-CEAS) has been developed for highly sensitive concentration measurements of carbon monoxide (CO) in a rapid compression machine. The duty cycle and the pulse repetition rate of the laser were optimized for increased tuning range, high chirp rate, and small line width to achieve effective laser-cavity coupling. This enabled spectrally resolved CO line-shape measurements at high pressures (P ~10 bar). A gain factor of 133 and a time resolution of 10 μs were demonstrated. CO concentration-time profiles during the oxidation of highly dilute n-octane/air mixtures were recorded, illustrating new opportunities in RCM experiments for chemical kinetics.

  14. Rapid Mapping of Lithiation Dynamics in Transition Metal Oxide Particles with Operando X-ray Absorption Spectroscopy

    Science.gov (United States)

    Nowack, Lea; Grolimund, Daniel; Samson, Vallerie; Marone, Federica; Wood, Vanessa

    2016-02-01

    Since the commercialization of lithium ion batteries (LIBs), layered transition metal oxides (LiMO2, where M = Co, Mn, Ni, or mixtures thereof) have been materials of choice for LIB cathodes. During cycling, the transition metals change their oxidation states, an effect that can be tracked by detecting energy shifts in the X-ray absorption near edge structure (XANES) spectrum. X-ray absorption spectroscopy (XAS) can therefore be used to visualize and quantify lithiation kinetics in transition metal oxide cathodes; however, in-situ measurements are often constrained by temporal resolution and X-ray dose, necessitating compromises in the electrochemistry cycling conditions used or the materials examined. We report a combined approach to reduce measurement time and X-ray exposure for operando XAS studies of lithium ion batteries. A highly discretized energy resolution coupled with advanced post-processing enables rapid yet reliable identification of the oxidation state. A full-field microscopy setup provides sub-particle resolution over a large area of battery electrode, enabling the oxidation state within many transition metal oxide particles to be tracked simultaneously. Here, we apply this approach to gain insights into the lithiation kinetics of a commercial, mixed-metal oxide cathode material, nickel cobalt aluminium oxide (NCA), during (dis)charge and its degradation during overcharge.

  15. Observation of reversible, rapid changes in drug susceptibility of hypoxic tumor cells in a microfluidic device.

    Science.gov (United States)

    Germain, Todd; Ansari, Megan; Pappas, Dimitri

    2016-09-14

    Hypoxia is a major stimulus for increased drug resistance and for survival of tumor cells. Work from our group and others has shown that hypoxia increases resistance to anti-cancer compounds, radiation, and other damage-pathway cytotoxic agents. In this work we utilize a microfluidic culture system capable of rapid switching of local oxygen concentrations to determine changes in drug resistance in prostate cancer cells. We observed rapid adaptation to hypoxia, with drug resistance to 2 μM staurosporine established within 30 min of hypoxia. Annexin-V/Sytox Green apoptosis assays over 9 h showed 78.0% viability, compared to 84.5% viability in control cells (normoxic cells with no staurosporine). Normoxic cells exposed to the same staurosporine concentration had a viability of 48.6% after 9 h. Hypoxia adaptation was rapid and reversible, with Hypoxic cells treated with 20% oxygen for 30 min responding to staurosporine with 51.6% viability after drug treatment for 9 h. Induction of apoptosis through the receptor-mediated pathway, which bypasses anti-apoptosis mechanisms induced by hypoxia, resulted in 39.4 ± 7% cell viability. The rapid reversibility indicates co-treatment of oxygen with anti-cancer compounds may be a potential therapeutic target. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. 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.

  17. Sunlight Induced Rapid Oil Absorption and Passive Room-Temperature Release: An Effective Solution toward Heavy Oil Spill Cleanup

    KAUST Repository

    Wu, Mengchun

    2018-05-18

    Rapid cleanup and easy recovery of spilled heavy oils is always a great challenge due to their high viscosity (>103 mPa s). One of the efficient methods to absorb highly viscous oils is to reduce their viscosity by increasing their temperature. In this work, the authors integrate the sunlight‐induced light‐to‐heat conversion effect of polypyrrole (PPy) and thermoresponsive property of poly(N‐isopropylacrylamide) (PNIPAm) into the melamine sponge, which successfully delivers a fast heavy oil absorption under sunlight and passive oil release underwater at room temperature. Thanks to the rationally designed functionalities, the PNIPAm/PPy functionalized sponges possess oleophilicity and hydrophobicity under sunlight. Due to the photothermal effect of PPy, the sponges locally heat up contacting heavy oil under sunlight and reduce its viscosity to a point where the oil voluntarily flow into the pores of the sponge. The material in this work is able to rapidly absorb the heavy oil with room temperature viscosity as high as ≈1.60 × 105 mPa s. The absorbed oil can be passively forced out the sponge underwater at room temperature due to the hydrophilicity of PNIPAm. The sunlight responsive and multifunctional sponge represents a meaningful attempt in coming up with a sustainable solution toward heavy oil spill.

  18. 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.

  19. Sunlight Induced Rapid Oil Absorption and Passive Room-Temperature Release: An Effective Solution toward Heavy Oil Spill Cleanup

    KAUST Repository

    Wu, Mengchun; Shi, Yusuf; Chang, Jian; Li, Renyuan; Ong, Chi Siang; Wang, Peng

    2018-01-01

    Rapid cleanup and easy recovery of spilled heavy oils is always a great challenge due to their high viscosity (>103 mPa s). One of the efficient methods to absorb highly viscous oils is to reduce their viscosity by increasing their temperature. In this work, the authors integrate the sunlight‐induced light‐to‐heat conversion effect of polypyrrole (PPy) and thermoresponsive property of poly(N‐isopropylacrylamide) (PNIPAm) into the melamine sponge, which successfully delivers a fast heavy oil absorption under sunlight and passive oil release underwater at room temperature. Thanks to the rationally designed functionalities, the PNIPAm/PPy functionalized sponges possess oleophilicity and hydrophobicity under sunlight. Due to the photothermal effect of PPy, the sponges locally heat up contacting heavy oil under sunlight and reduce its viscosity to a point where the oil voluntarily flow into the pores of the sponge. The material in this work is able to rapidly absorb the heavy oil with room temperature viscosity as high as ≈1.60 × 105 mPa s. The absorbed oil can be passively forced out the sponge underwater at room temperature due to the hydrophilicity of PNIPAm. The sunlight responsive and multifunctional sponge represents a meaningful attempt in coming up with a sustainable solution toward heavy oil spill.

  20. 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.

  1. 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.

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

    International Nuclear Information System (INIS)

    Li, Xiaoguang; Qian, Hua; Miyamoto, Fusako; Naito, Takeshi; Kawaji, Kumi; Kajiwara, Kazumi; Hattori, Toshio; Matsuoka, Masao; Watanabe, Kentaro; Oishi, Shinya; Fujii, Nobutaka

    2012-01-01

    Highlights: ► We established a novel, simple and rapid in vivo system for evaluation of anti-HIV-1 drugs with rats. ► The system may be applicable for other antiviral drugs, and/or useful for initial screening in vivo. ► 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 IIIB and HIV-1 BaL as representative CXCR4- and CCR5-tropic HIV-1 strains, respectively. CXCR4 antagonists were shown to only possess anti-HIV-1 IIIB activity, whereas fusion inhibitors showed both anti-HIV-1 IIIB and anti-HIV-1 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.

  3. [Experience of rapid drug desensitization therapy in the treatment of mycobacterial disease].

    Science.gov (United States)

    Sasaki, Yuka; Kurashima, Atsuyuki; Morimoto, Kozo; Okumura, Masao; Watanabe, Masato; Yoshiyama, Takashi; Ogata, Hideo; Gotoh, Hajime; Kudoh, Shoji; Suzuki, Hiroaki

    2014-11-01

    Drugs for tuberculosis and non-tuberculosis mycobacterial diseases are limited. In particular, no new drugs for non-tuberculosis mycobacterial disease have been developed in recent years. Antimycobacterial drugs have many adverse reactions, for which drug desensitization therapy has been used. Rapid drug desensitization (RDD) therapy, including antituberculosis drugs and clarithromycin, has been implemented in many regions in Europe and the United States. We investigated the validity of RDD therapy in Japan. We report our experience with RDD therapy in 13 patients who developed severe drug allergy to antimycobacterial treatment. The desensitization protocol reported by Holland and Cernandas was adapted. The underlying diseases were 7 cases of pulmonary Mycobacterium avium complex disease and 6 cases of pulmonary tuberculosis. Isoniazid was readministered in 2 (100%) of 2 patients; rifampicin, in 8 (67.7%) of 12 patients; ethambutol, in 4 (67.7%) of 6 patients; and clarithromycin, in 2 (100%) of 2 patients. In Japan, the desensitization therapy recommended by the Treatment Committee of the Japanese Society for Tuberculosis have been implemented generally. We think RDD therapy is effective and safe as the other desensitization therapy. We will continue to investigate the efficiency of RDD therapy in patients who had discontinued antimycobacterial treatment because of the drug allergic reaction.

  4. 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...

  5. Rapid analysis of pharmaceutical drugs using LIBS coupled with multivariate analysis.

    Science.gov (United States)

    Tiwari, P K; Awasthi, S; Kumar, R; Anand, R K; Rai, P K; Rai, A K

    2018-02-01

    Type 2 diabetes drug tablets containing voglibose having dose strengths of 0.2 and 0.3 mg of various brands have been examined, using laser-induced breakdown spectroscopy (LIBS) technique. The statistical methods such as the principal component analysis (PCA) and the partial least square regression analysis (PLSR) have been employed on LIBS spectral data for classifying and developing the calibration models of drug samples. We have developed the ratio-based calibration model applying PLSR in which relative spectral intensity ratios H/C, H/N and O/N are used. Further, the developed model has been employed to predict the relative concentration of element in unknown drug samples. The experiment has been performed in air and argon atmosphere, respectively, and the obtained results have been compared. The present model provides rapid spectroscopic method for drug analysis with high statistical significance for online control and measurement process in a wide variety of pharmaceutical industrial applications.

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

    International Nuclear Information System (INIS)

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

    2015-01-01

    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. (paper)

  7. Evaluation of the microscopic observational drug susceptibility assay for rapid and efficient diagnosis of multi-drug resistant tuberculosis

    Directory of Open Access Journals (Sweden)

    R P Lazarus

    2012-01-01

    Full Text Available Purpose: Tuberculosis (TB is endemic in India and the burden of multi-drug-resistant tuberculosis (MDR-TB is high. Early detection of MDR-TB is of primary importance in controlling the spread of TB. The microscopic observational drug susceptibility (MODS assay has been described as a cost-effective and rapid method by which mycobacterial culture and the drug susceptibility test (DST can be done at the same time. Materials and Methods: A total of 302 consecutive sputum samples that were received in an accredited mycobacteriology laboratory for conventional culture and DST were evaluated by the MODS assay. Results: In comparison with conventional culture on Lowenstein Jensen (LJ media, the MODS assay showed a sensitivity of 94.12% and a specificity of 89.39% and its concordance with the DST by the proportion method on LJ media to isoniazid and rifampicin was 90.8% and 91.5%, respectively. The turnaround time for results by MODS was 9 days compared to 21 days by culture on LJ media and an additional 42 days for DST by the 1% proportion method. The cost of performing a single MODS assay was Rs. 250/-, compared to Rs. 950/- for culture and 1st line DST on LJ. Conclusion: MODS was found to be a sensitive and rapid alternative method for performing culture and DST to identify MDR-TB in resource poor settings.

  8. Erbium:YAG laser resurfacing increases skin permeability and the risk of excessive absorption of antibiotics and sunscreens: the influence of skin recovery on drug absorption.

    Science.gov (United States)

    Lee, Woan-Ruoh; Shen, Shing-Chuan; Al-Suwayeh, Saleh A; Li, Yi-Ching; Fang, Jia-You

    2012-06-01

    While laser skin resurfacing is expected to result in reduced barrier function and increased risk of drug absorption, the extent of the increment has not yet been systematically investigated. We aimed to establish the skin permeation profiles of tetracycline and sunscreens after exposure to the erbium:yttrium-aluminum-garnet (Er:YAG) laser during postoperative periods. Physiological and histopathological examinations were carried out for 5 days after laser treatment on nude mice. Percutaneous absorption of the permeants was determined by an in vitro Franz cell. Ablation depths varied in reaching the stratum corneum (10 μm, 2.5 J/cm²) to approach the epidermis (25 μm, 6.25 J/cm²) and upper dermis (40 μm, 10 J/cm²). Reepithelialization evaluated by transepidermal water loss was complete within 2-4 days and depended on the ablation depth. Epidermal hyperplasia was observed in the 40-μm-treated group. The laser was sufficient to disrupt the skin barrier and allow the transport of the permeants into and across the skin. The laser fluence was found to play an important role in modulating skin absorption. A 25-μm ablation depth increased tetracycline flux 84-fold. A much smaller enhancement (3.3-fold) was detected for tetracycline accumulation within the skin. The laser with different fluences produced enhancement of oxybenzone skin deposition of 3.4-6.4-fold relative to the untreated group. No penetration across the skin was shown regardless of whether titanium dioxide was applied to intact or laser-treated skin. However, laser resurfacing increased the skin deposition of titanium dioxide from 46 to 109-188 ng/g. Tetracycline absorption had recovered to the level of intact skin after 5 days, while more time was required for oxybenzone absorption. The in vivo skin accumulation and plasma concentration revealed that the laser could increase tetracycline absorption 2-3-fold. The experimental results indicated that clinicians should be cautious when determining the

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

    Science.gov (United States)

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

    2018-01-01

    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. 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 © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  10. Effects of PEGylated lipid nanoparticles on the oral absorption of one BCS II drug: a mechanistic investigation

    Directory of Open Access Journals (Sweden)

    Zhang XW

    2014-11-01

    Full Text Available Xingwang Zhang,* Guijiang Chen,* Tianpeng Zhang, Zhiguo Ma, Baojian WuDivision of Pharmaceutics, College of Pharmacy, Jinan University, Guangzhou, People’s Republic of China*These authors contributed equally to this workAbstract: Lipid nanocarriers are becoming a versatile platform for oral delivery of lipophilic drugs. In this article, we aimed to explore the gastrointestinal behaviors of lipid nanoparticles and the effect of PEGylation on oral absorption of fenofibrate (FN, a Biopharmaceutics Classification System (BCS II model drug. FN-loaded PEGylated lipid nanoparticles (FN-PLNs were prepared by the solvent-diffusion method and characterized by particle size distribution, morphology, Fourier transform infrared spectroscopy, and drug release. Lipolytic experiments were performed to assess the resistance of lipid nanoparticles against pancreatic lipase. Pharmacokinetics was evaluated in rats after oral administration of FN preparations. The obtained FN-PLNs were 186.7 nm in size with an entrapment efficiency of >95%. Compared to conventional lipid nanoparticles, PLNs exhibited slower drug release in the lipase-containing medium, strikingly reduced mucin binding, and suppressed lipolysis in vitro. Further, oral absorption of FN was significantly enhanced using PLNs with relative bioavailability of 123.9% and 157.0% to conventional lipid nanoparticles and a commercial formulation (Lipanthyl®, respectively. It was demonstrated that reduced mucin trapping, suppressed lipolysis, and/or improved mucosal permeability were responsible for increased oral absorption. These results facilitated a better understanding of the in vivo fate of lipid nanoparticles, and suggested the potential of PLNs as oral carriers of BCS II drugs.Keywords: fenofibrate, lipid nanoparticles, PEGylation, oral bioavailability, absorption mechanism

  11. 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.

  12. Rapid assessment response (RAR study: drug use and health risk - Pretoria, South Africa

    Directory of Open Access Journals (Sweden)

    Trautmann Franz

    2011-06-01

    Full Text Available Abstract Background Within a ten year period South Africa has developed a substantial illicit drug market. Data on HIV risk among drug using populations clearly indicate high levels of HIV risk behaviour due to the sharing of injecting equipment and/or drug-related unprotected sex. While there is international evidence on and experience with adequate responses, limited responses addressing drug use and drug-use-related HIV and other health risks are witnessed in South Africa. This study aimed to explore the emerging problem of drug-related HIV transmission and to stimulate the development of adequate health services for the drug users, by linking international expertise and local research. Methods A Rapid Assessment and Response (RAR methodology was adopted for the study. For individual and focus group interviews a semi-structured questionnaire was utilised that addressed key issues. Interviews were conducted with a total of 84 key informant (KI participants, 63 drug user KI participants (49 males, 14 females and 21 KI service providers (8 male, 13 female. Results and Discussion Adverse living conditions and poor education levels were cited as making access to treatment harder, especially for those living in disadvantaged areas. Heroin was found to be the substance most available and used in a problematic way within the Pretoria area. Participants were not fully aware of the concrete health risks involved in drug use, and the vague ideas held appear not to allow for concrete measures to protect themselves. Knowledge with regards to substance related HIV/AIDS transmission is not yet widespread, with some information sources disseminating incorrect or unspecific information. Conclusions The implementation of pragmatic harm-reduction and other evidence-based public health care policies that are designed to reduce the harmful consequences associated with substance use and HIV/AIDS should be considered. HIV testing and treatment services also need to

  13. A study of the energy absorption and exposure buildup factors of some anti-inflammatory drugs

    International Nuclear Information System (INIS)

    Ekinci, Neslihan; Kavaz, Esra; Özdemir, Yüksel

    2014-01-01

    Human radiation exposure is increasing due to radiation development in science and technology. The development of radioprotective agents is important for protecting patients from the side effects of radiotherapy and for protecting the public from unwanted irradiation. Radioprotective agents are used to reduce the damage caused by radiation in healthy tissues. There are several classes of radioprotective compounds that are under investigation. Analgesics and anti-inflammatory compounds are being considered for treating or preventing the effects of damage due to radiation exposure, or for increasing the chance of survival after exposure to a high dose of radiation. In this study, we investigated the radioprotective effects of some analgesic and anti-inflammatory compounds by evaluating buildup factors. The gamma ray energy absorption (EABF) and exposure buildup factors (EBF) were calculated to select compounds in a 0.015–15 MeV energy region up to a penetration depth of 40 mfp (mean free path). Variations of EABF and EBF with incident photon energy and penetration depth elements were also investigated. Significant variations in both EABF and EBF values were observed for several compounds at the moderate energy region. At energies below 0.15 MeV, EABF and EBF values increased with decreasing equivalent atomic number (Z eq ) of the samples. In addition, EABF and EBF were the largest for ibuprofen, aspirin, paracetamol, naproxen and ketoprofen at 0.05 and 0.06 MeV, respectively, and the EABF value was 0.1 MeV for aceclofenac. From these results, we concluded that the buildup of photons is less for aceclofenac compared to other materials. - Highlights: • Buildup factors of anti-inflammatory drugs have been calculated by a G-P fitting method. • Z eff of diclofenac was observed higher than other compounds. • It was found that buildup of photons is less for aceclofenac and diclofenac. • It would be appealing to use aceclofenac and diclofenac as radioprotective

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

    Directory of Open Access Journals (Sweden)

    R Bartholomé

    Full Text Available 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.

  15. Rapid screening of pharmaceutical drugs using thermal desorption – SALDI mass spectrometry

    International Nuclear Information System (INIS)

    Grechnikov, A A; Kubasov, A E; Borodkov, A S; Georgieva, V B; Nikiforov, S M; Simanovsky, Ya O; Alimpiev, S S

    2012-01-01

    A novel approach to the rapid screening of pharmaceutical drugs by surface assisted laser desorption-ionization (SALDI) mass spectrometry with the rotating ball interface coupled with temperature programmed thermal desorption has been developed. Analytes were thermally desorbed and deposited onto the surface of amorphous silicon substrate attached to the rotating ball. The ball was rotated and the deposited analytes were analyzed using SALDI. The effectiveness of coupling SALDI mass spectrometry with thermal desorption was evaluated by the direct and rapid analysis of tablets containing lidocaine, diphenhydramine and propranolol without any sample pretreatment. The overall duration of the screening procedure was 30÷40 sec. Real urine samples were studied for drug analysis. It is shown that with simple preparation steps, urine samples can be quantitatively analyzed using the proposed technique with the detection limits in the range of 0.2÷0.5 ng/ml.

  16. In vivo assessment of the impact of efflux transporter on oral drug absorption using portal vein-cannulated rats.

    Science.gov (United States)

    Matsuda, Yoshiki; Konno, Yoshihiro; Hashimoto, Takashi; Nagai, Mika; Taguchi, Takayuki; Satsukawa, Masahiro; Yamashita, Shinji

    2013-08-01

    The purpose of this study was to evaluate the impact of intestinal efflux transporters on the in vivo oral absorption process. Three model drugs-fexofenadine (FEX), sulfasalazine (SASP), and topotecan (TPT)-were selected as P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and P-gp and BCRP substrates, respectively. The drugs were orally administered to portal vein-cannulated rats after pretreatment with zosuquidar (ZSQ), P-gp inhibitor, and/or Ko143, BCRP inhibitor. Intestinal availability (Fa·Fg) of the drugs was calculated from the difference between portal and systemic plasma concentrations. When rats were orally pretreated with ZSQ, Fa·Fg of FEX increased 4-fold and systemic clearance decreased to 75% of the control. In contrast, intravenous pretreatment with ZSQ did not affect Fa·Fg of FEX, although systemic clearance decreased significantly. These data clearly show that the method presented herein using portal vein-cannulated rats can evaluate the effects of intestinal transporters on Fa·Fg of drugs independently of variable systemic clearance. In addition, it was revealed that 71% of FEX taken up into enterocytes underwent selective efflux via P-gp to the apical surface, while 79% of SASP was effluxed by Bcrp. In the case of TPT, both transporters were involved in its oral absorption. Quantitative analysis indicated a 3.5-fold higher contribution from Bcrp than P-gp. In conclusion, the use of portal vein-cannulated rats enabled the assessment of the impact of efflux transporters on intestinal absorption of model drugs. This experimental system is useful for clarifying the cause of low bioavailability of various drugs.

  17. Global transcriptional profiling of longitudinal clinical isolates of Mycobacterium tuberculosis exhibiting rapid accumulation of drug resistance.

    Directory of Open Access Journals (Sweden)

    Anirvan Chatterjee

    Full Text Available The identification of multidrug resistant (MDR, extensively and totally drug resistant Mycobacterium tuberculosis (Mtb, in vulnerable sites such as Mumbai, is a grave threat to the control of tuberculosis. The current study aimed at explaining the rapid expression of MDR in Directly Observed Treatment Short Course (DOTS compliant patients, represents the first study comparing global transcriptional profiles of 3 pairs of clinical Mtb isolates, collected longitudinally at initiation and completion of DOTS. While the isolates were drug susceptible (DS at onset and MDR at completion of DOTS, they exhibited identical DNA fingerprints at both points of collection. The whole genome transcriptional analysis was performed using total RNA from H37Rv and 3 locally predominant spoligotypes viz. MANU1, CAS and Beijing, hybridized on MTBv3 (BuG@S microarray, and yielded 36, 98 and 45 differentially expressed genes respectively. Genes encoding transcription factors (sig, rpoB, cell wall biosynthesis (emb genes, protein synthesis (rpl and additional central metabolic pathways (ppdK, pknH, pfkB were found to be down regulated in the MDR isolates as compared to the DS isolate of the same genotype. Up regulation of drug efflux pumps, ABC transporters, trans-membrane proteins and stress response transcriptional factors (whiB in the MDR isolates was observed. The data indicated that Mtb, without specific mutations in drug target genes may persist in the host due to additional mechanisms like drug efflux pumps and lowered rate of metabolism. Furthermore this population of Mtb, which also showed reduced DNA repair activity, would result in selection and stabilization of spontaneous mutations in drug target genes, causing selection of a MDR strain in the presence of drug pressures. Efflux pump such as drrA may play a significant role in increasing fitness of low level drug resistant cells and assist in survival of Mtb till acquisition of drug resistant mutations with

  18. Supersaturation-nucleation behavior of poorly soluble drugs and its impact on the oral absorption of drugs in thermodynamically high-energy forms.

    Science.gov (United States)

    Ozaki, Shunsuke; Minamisono, Takuma; Yamashita, Taro; Kato, Takashi; Kushida, Ikuo

    2012-01-01

    In order to better understand the oral absorption behavior of poorly water-soluble drugs, their supersaturation-nucleation behavior was characterized in fasted state simulated intestinal fluid. The induction time (t(ind)) for nucleation was measured for four model drugs: itraconazole, erlotinib, troglitazone, and PLX4032. Supersaturated solutions were prepared by solvent shift method, and nucleation initiation was monitored by ultraviolet detection. The relationship between t(ind) and degree of supersaturation was analyzed in terms of classical nucleation theory. The defined supersaturation stability proved to be compound specific. Clinical data on oral absorption were investigated for drugs in thermodynamically high-energy forms such as amorphous forms and salts and was compared with in vitro supersaturation-nucleation characteristics. Solubility-limited maximum absorbable dose was proportionate to intestinal effective drug concentrations, which are related to supersaturation stability and thermodynamic solubility. Supersaturation stability was shown to be an important factor in determining the effect of high-energy forms. The characterization of supersaturation-nucleation behavior by the presented method is, therefore, valuable for assessing the potential absorbability of poorly water-soluble drugs. Copyright © 2011 Wiley-Liss, Inc.

  19. A rapid in vitro screening system for the identification and evaluation of anticancer drugs

    International Nuclear Information System (INIS)

    Kao, J.W.; Collins, J.L.

    1989-01-01

    We report the development of an in vitro screening system that can be used to identify new anticancer drugs that are specifically cytotoxic for dividing cells. The screening system takes advantage of the potential of many cell lines, including tumor cells, to stop dividing when they are plated at high cell density. The cytotoxic effects of anticancer drugs on dividing (i.e., cells plated at low cell density) and nondividing cells (i.e., cells plated at high cell density) is measured by the incorporation of 51Cr. This in vitro system was evaluated by measuring the cytotoxic effects of the anticancer drugs cisplatin, thiotepa, doxorubicin, methotrexate, and vinblastine on the cell lines B/C-N, ME-180, and MCF-7. In this in vitro system the concentrations of the anticancer drugs that produced significant cytotoxicity on only dividing cells are similar to the concentrations that are used clinically. The fact that this in vitro system is rapid, simple, applicable to many cell types, and able to predict effective concentrations of anticancer drugs should make it useful for the screening of new anticancer drugs and for the design of preclinical studies

  20. A review of advanced oral drug delivery technologies facilitating the protection and absorption of protein and peptide molecules.

    Science.gov (United States)

    Choonara, Bibi F; Choonara, Yahya E; Kumar, Pradeep; Bijukumar, Divya; du Toit, Lisa C; Pillay, Viness

    2014-11-15

    The oral delivery of proteins and peptides is a dynamic research field despite the numerous challenges limiting their effective delivery. Successful oral delivery of proteins and peptides requires the accomplishment of three key tasks: protection of the macromolecules from degradation in the gastrointestinal tract (GIT), permeation through the intestinal barrier and absorption of molecules into the systemic circulation. Currently, no clinically useful oral formulations have been developed but several attempts have been made to overcome the challenges of low oral bioavailability resulting from poor absorption, poor permeation and enzymatic degradation of the proteins and peptides in the GIT. Present strategies attempt to provide structural protection of the proteins and peptides and improved absorption through the use of enzyme inhibitors, absorption enhancers, novel polymeric delivery systems and chemical modification. However, each of these technologies has their limitations despite showing positive results. This review attempts to discuss the physical and chemical barriers of the GIT with particular emphasis on the current approaches employed to overcome these barriers, including the evaluation of other non-parenteral routes of protein and peptide delivery. In addition, this review assimilates oral formulation strategies under development and within the clinical trial stage in relation to their benefits and drawbacks with regard to facilitating optimal protection and absorption of proteins and peptides, as well as pertinent future challenges and opportunities governing oral drug delivery. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Self-reported drug use among secondary school students in two rapidly developing Nigerian towns.

    Science.gov (United States)

    Nevadomsky, J

    1982-01-01

    A 32-item standardized multiple-choice and open-ended questionnaire was completed by nearly 500 male and female secondary school students in two rapidly developing Nigerian towns. About two thirds of the students reported some exposure to alcohol, and about one quarter reported some experience with tobacco. There was much less use of caffeine, methaqualone in combination with diphenhydramine, 2-ethylamino-3-phenylorcamphane in combination with vitamins, chlordiazepoxide, diazepam, cannabis and dexamphetamine. Many students fell into the "past use" category. Parents were extremely disapproving of the use of almost any drug. Many students supported stronger penalties for the use of cannabis. Non-users claimed that drugs were dangerous to health. In addition, religious beliefs were associated with abstinence from drugs.

  2. 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.

  3. Single and Double Infrared Transitions in Rapid Vapor Deposited Parahydrogen Solids: Application to Sample Thickness Determination and Quantitative Infrared Absorption Spectroscopy

    National Research Council Canada - National Science Library

    Tam, Simon

    2001-01-01

    ...) solid from its infrared (IR) absorption spectrum. Millimeters-thick pH2 solids of exceptional optical clarity can be produced by the rapid vapor deposition method M.E. Fajardo and S. Tam, J. Chem. Phys. 108, 4237 (1998...

  4. 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

  5. Mechanism of enhanced oral absorption of morin by phospholipid complex based self-nanoemulsifying drug delivery system.

    Science.gov (United States)

    Zhang, Jinjie; Li, Jianbo; Ju, Yuan; Fu, Yao; Gong, Tao; Zhang, Zhirong

    2015-02-02

    Phospholipid complex (PLC) based self-nanoemulsifying drug delivery system (PLC-SNEDDS) has been developed for efficient delivery of drugs with poor solubility and low permeability. In the present study, a BCS class IV drug and a P-glycoprotein (P-gp) substrate, morin, was selected as the model drug to elucidate the oral absorption mechanism of PLC-SNEDDS. PLC-SNEDDS was superior to PLC in protecting morin from degradation by intestinal enzymes in vitro. In situ perfusion study showed increased intestinal permeability by PLC was duodenum-specific. In contrast, PLC-SNEDDS increased morin permeability in all intestinal segments and induced a change in the main absorption site of morin from colon to ileum. Moreover, ileum conducted the lymphatic transport of PLC-SNEDDS, which was proven by microscopic intestinal visualization of Nile red labeled PLC-SNEDDS and lymph fluids in vivo. Low cytotoxicity and increased Caco-2 cell uptake suggested a safe and efficient delivery of PLC-SNEDDS. The increased membrane fluidity and disrupted actin filaments were closely associated with the increased cell uptake of PLC-SNEDDS. PLC-SNEDDS could be internalized into enterocytes as an intact form in a cholesterol-dependent manner via clathrin-mediated endocytosis and macropinocytosis. The enhanced oral absorption of morin was attributed to the P-gp inhibition by Cremophor RH and the intact internalization of M-PLC-SNEDDS into Caco-2 cells bypassing P-gp recognition. Our findings thus provide new insights into the development of novel nanoemulsions for poorly absorbed drugs.

  6. Rapid drug desensitization for hypersensitivity reactions to chemotherapy and monoclonal antibodies in the 21st century.

    Science.gov (United States)

    Castells Guitart, M C

    2014-01-01

    The frequency of hypersensitivity reactions (HSR) to drugs has risen in the last 10 years owing to increased exposure to better and more allergenic medications including monoclonal antibodies. HSRs prevent patients from using their first-line therapy, leading to decreased quality of life and life expectancy. Although premedication with antihistamines, leukotriene blockers, and corticosteroids can protect against mild-to-moderate HSR, none of these medications has provided protection against anaphylaxis. Rapid drug desensitization is a treatment option for patients with HSR to their first-line medication that protects against anaphylaxis.Although the mechanisms of drug desensitization are not completely understood, in vitro mast cell models of IgE antigen desensitization have led to the design of safe and effective in vivo protocols aimed at protecting highly sensitized patients from hypersensitivity reactions and anaphylaxis. This review provides an insight into the mechanisms of IgE/mast cell desensitization, the principles and practice of drug desensitization, and an overview of the different desensitization protocols and their safety and efficacy profiles. Drug desensitization should only be performed by allergists, trained nurses, and experienced pharmacists, since this high-risk procedure involves reintroducing allergenic medication to highly sensitized patients, with the consequent potential for severe or fatal HSRs.

  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. 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.

  9. Embryonic Zebrafish Model - A Well-Established Method for Rapidly Assessing the Toxicity of Homeopathic Drugs

    Science.gov (United States)

    Gupta, Himanshu R; Patil, Yogesh; Singh, Dipty

    2016-01-01

    in this study. The embryonic zebrafish model is recommended as a well-established method for rapidly assessing the toxicity of homeopathic drugs. PMID:28127503

  10. Rapid increase in the use of oral antidiabetic drugs in the United States, 1990-2001.

    Science.gov (United States)

    Wysowski, Diane K; Armstrong, George; Governale, Laura

    2003-06-01

    To describe the use of oral antidiabetic drugs for management of type 2 diabetes in the U.S. from 1990 through 2001. Data on oral antidiabetic drugs were derived from two pharmaceutical marketing databases from IMS Health, the National Prescription Audit Plus and the National Disease and Therapeutic Index. In 1990, 23.4 million outpatient prescriptions of oral antidiabetic agents were dispensed. By 2001, this number had increased 3.9-fold, to 91.8 million prescriptions. Glipizide and glyburide, two sulfonylurea medications, accounted for approximately 77% of prescriptions of oral antidiabetic drugs in 1990 and 35.5% of prescriptions in 2001. By 2001, the biguanide metformin (approved in 1995) had captured approximately 33% of prescriptions, and the thiazolidinedione insulin sensitizers (rosiglitazone and pioglitazone marketed beginning in 1999) accounted for approximately 17% of market share. Compared with patients treated in 1990, those in 2001 were proportionately younger and they more often used oral antidiabetic drugs and insulin in combination. Internists and general and family practitioners were the primary prescribers of this class of drugs. Consistent with the reported increase in the prevalence of type 2 diabetes, the number of dispensed outpatient prescriptions of oral antidiabetic drugs increased rapidly between 1990 and 2001. This period was marked by an increase in the treatment of younger people and the use of oral antidiabetic drugs in combination. With the approval in the last decade of several new types of oral antidiabetic medications with different mechanisms of action, options for management of type 2 diabetes have expanded.

  11. Rapid molecular diagnostics for multi-drug resistant tuberculosis in India.

    Science.gov (United States)

    Ramachandran, Rajeswari; Muniyandi, M

    2018-03-01

    Rapid molecular diagnostic methods help in the detection of TB and Rifampicin resistance. These methods detect TB early, are accurate and play a crucial role in reducing the burden of drug resistant tuberculosis. Areas covered: This review analyses rapid molecular diagnostic tools used in the diagnosis of MDR-TB in India, such as the Line Probe Assay and GeneXpert. We have discussed the burden of MDR-TB and the impact of recent diagnostic tools on case detection and treatment outcomes. This review also discusses the costs involved in establishing these new techniques in India. Expert commentary: Molecular methods have considerable advantages for the programmatic management of drug resistant TB. These include speed, standardization of testing, potentially high throughput and reduced laboratory biosafety requirements. There is a desperate need for India to adopt modern, rapid, molecular tools with point-of-care tests being currently evaluated. New molecular diagnostic tests appear to be cost effective and also help in detecting missing cases. There is enough evidence to support the scaling up of these new tools in India.

  12. Effects of gastric pH on oral drug absorption: In vitro assessment using a dissolution/permeation system reflecting the gastric dissolution process.

    Science.gov (United States)

    Kataoka, Makoto; Fukahori, Miho; Ikemura, Atsumi; Kubota, Ayaka; Higashino, Haruki; Sakuma, Shinji; Yamashita, Shinji

    2016-04-01

    The aim of the present study was to evaluate the effects of gastric pH on the oral absorption of poorly water-soluble drugs using an in vitro system. A dissolution/permeation system (D/P system) equipped with a Caco-2 cell monolayer was used as the in vitro system to evaluate oral drug absorption, while a small vessel filled with simulated gastric fluid (SGF) was used to reflect the gastric dissolution phase. After applying drugs in their solid forms to SGF, SGF solution containing a 1/100 clinical dose of each drug was mixed with the apical solution of the D/P system, which was changed to fasted state-simulated intestinal fluid. Dissolved and permeated amounts on applied amount of drugs were then monitored for 2h. Similar experiments were performed using the same drugs, but without the gastric phase. Oral absorption with or without the gastric phase was predicted in humans based on the amount of the drug that permeated in the D/P system, assuming that the system without the gastric phase reflected human absorption with an elevated gastric pH. The dissolved amounts of basic drugs with poor water solubility, namely albendazole, dipyridamole, and ketoconazole, in the apical solution and their permeation across a Caco-2 cell monolayer were significantly enhanced when the gastric dissolution process was reflected due to the physicochemical properties of basic drugs. These amounts resulted in the prediction of higher oral absorption with normal gastric pH than with high gastric pH. On the other hand, when diclofenac sodium, the salt form of an acidic drug, was applied to the D/P system with the gastric phase, its dissolved and permeated amounts were significantly lower than those without the gastric phase. However, the oral absorption of diclofenac was predicted to be complete (96-98%) irrespective of gastric pH because the permeated amounts of diclofenac under both conditions were sufficiently high to achieve complete absorption. These estimations of the effects of

  13. 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

    Vigabatrin is an antiepileptic drug substance mainly used in pediatric treatment of infantile spasms. The main source of nutrition for infants is breast milk and/or infant formula. Our hypothesis was that infant formula may affect the intestinal absorption of vigabatrin. The aim was therefore...... to investigate the potential effect of coadministration of infant formula with vigabatrin on the oral absorption in vitro and in vivo. The effect of vigabatrin given with an infant formula on the oral uptake and transepithelial transport was investigated in vitro in Caco-2 cells. In vivo effects of infant...... formula and selected amino acids on the pharmacokinetic profile of vigabatrin was investigated after oral coadministration to male Sprague–Dawley rats using acetaminophen as a marker for gastric emptying. The presence of infant formula significantly reduced the uptake rate and permeability of vigabatrin...

  14. Aminoclay–lipid hybrid composite as a novel drug carrier of fenofibrate for the enhancement of drug release and oral absorption

    Directory of Open Access Journals (Sweden)

    Yang L

    2016-03-01

    Full Text Available Liang Yang, Yating Shao, Hyo-Kyung Han BK Plus Project Team, College of Pharmacy, Dongguk University, Goyang, South Korea Abstract: This study aimed to prepare the aminoclay–lipid hybrid composite to enhance the drug release and improve the oral bioavailability of poorly water-soluble fenofibrate. Antisolvent precipitation coupled with an immediate freeze-drying method was adopted to incorporate fenofibrate into aminoclay–lipid hybrid composite (ALC. The optimal composition of the ALC formulation was determined as the ratios of aminoclay to krill oil of 3:1 (w/w, krill oil to fenofibrate of 2:1 (w/w, and antisolvent to solvent of 6:4 (v/v. The morphological characteristics of ALC formulation were determined using scanning electron microscopy, differential scanning calorimetry, and X-ray powder diffraction, which indicated microcrystalline state of fenofibrate in ALC formulation. The ALC formulation achieved almost complete dissolution within 30 minutes, whereas the untreated powder and physical mixture exhibited less than 15% drug release. Furthermore, ALC formulation effectively increased the peak plasma concentration (Cmax and area under the curve (AUC of fenofibric acid (an active metabolite in rats by approximately 13- and seven-fold, respectively. Furthermore, ALC formulation exhibited much lower moisture sorption behavior than the lyophilized formulation using sucrose as a cryoprotectant. Taken together, the present findings suggest that ALC formulation is promising for improving the oral absorption of poorly soluble fenofibrate. Keywords: aminoclay, omega-3 phospholipids, fenofibrate, drug release, oral absorption 

  15. 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

    2012-10-01

    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, in particular, BCS class II weak acids. However, a discrepancy between the in vivo BE results and in vitro dissolution results for 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 of 6.0. Further the experimental dissolution of ibuprofen tablets in a low concentration phosphate buffer at pH 6.0 (the average buffer capacity 2.2 mmol l (-1) /pH) was dramatically reduced compared with the dissolution in SIF (the average buffer capacity 12.6 mmol l (-1) /pH). Thus these predictions for the oral absorption of BCS class II acids indicate that the absorption patterns depend largely on the intestinal pH and buffer strength and must be considered carefully for a bioequivalence test. Simulation software may be a very useful tool to aid the selection of dissolution media that may be useful in setting an in vitro bioequivalence dissolution standard. Copyright © 2012 John Wiley & Sons, Ltd.

  16. 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

  17. Sex, drugs, and HIV: rapid assessment of HIV risk behaviors among street-based drug using sex workers in Durban, South Africa.

    Science.gov (United States)

    Needle, Richard; Kroeger, Karen; Belani, Hrishikesh; Achrekar, Angeli; Parry, Charles D; Dewing, Sarah

    2008-11-01

    South Africa is experiencing significant changes in patterns of illicit drug use, including increasing injection and non-injection drug use, and the use of drugs by persons engaged in sex work, both of which could further expand the HIV/AIDS epidemic. In 2005, a rapid ethnographic assessment was conducted in Durban, South Africa, to learn more about patterns of drug use and HIV risk behaviors among drug-using, street-based sex workers. Field teams recruited 52 current injection and non-injection drug users for key informant interviews and focus groups, and they conducted mapping and observation in identified high-risk neighborhoods. Key informants were offered free, voluntary counseling and HIV rapid testing. The results of the assessment indicate that in this population, drugs play an organizing role in patterns of daily activities, with sex work closely linked to the buying, selling, and using of drugs. Participants reported using multiple drugs including crack cocaine, heroin, Ecstasy and Mandrax, and their choices were based on their expectations about the functional role and behavioral and pharmacological properties of the drugs. The organization of sex work and patterns of drug use differ by gender, with males exercising more control over daily routines and drug and sexual transactions than females. Activities of female sex workers are subject to considerable control by individual pimps, many of whom also function as landlords and drug dealers. A strong hold over the overlapping economies of drugs and sex work by a few individuals extends to control of the physical and social settings in which sex is exchanged and drugs are sold and used as well as the terms under which sex work is carried out. The potential for accelerated HIV spread is considerable given the evidence of overlapping drug-using and sexual risk behaviors and the mixing patterns across drug and sexual risk networks.

  18. The contribution of the in-vivo fate of an oil depot to drug absorption

    NARCIS (Netherlands)

    Kalicharan, R. W.; Oussoren, C; Schot, Peter; Rijk, de, E.; Vromans, H.

    2017-01-01

    Sustained release of lipophilic compounds can be achieved with oil depots. These parenteral formulations are generally injected in the vastus lateralis and deltoid muscle. It is known that the absorption rate differs between these two muscles. The reason for this is not fully understood. The aim of

  19. Rapid phospho-turnover by receptor tyrosine kinases impacts downstream signaling and drug binding.

    Science.gov (United States)

    Kleiman, Laura B; Maiwald, Thomas; Conzelmann, Holger; Lauffenburger, Douglas A; Sorger, Peter K

    2011-09-02

    Epidermal growth factor receptors (ErbB1-4) are oncogenic receptor tyrosine kinases (RTKs) that regulate diverse cellular processes. In this study, we combine measurement and mathematical modeling to quantify phospho-turnover at ErbB receptors in human cells and to determine the consequences for signaling and drug binding. We find that phosphotyrosine residues on ErbB1 have half-lives of a few seconds and therefore turn over 100-1000 times in the course of a typical immediate-early response to ligand. Rapid phospho-turnover is also observed for EGF-activated ErbB2 and ErbB3, unrelated RTKs, and multiple intracellular adaptor proteins and signaling kinases. Thus, the complexes formed on the cytoplasmic tail of active receptors and the downstream signaling kinases they control are highly dynamic and antagonized by potent phosphatases. We develop a kinetic scheme for binding of anti-ErbB1 drugs to receptors and show that rapid phospho-turnover significantly impacts their mechanisms of action. Copyright © 2011 Elsevier Inc. All rights reserved.

  20. 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%.

  1. Rapid and simple clean-up and derivatizaton procedure for the gas chromatographic determination of acidic drugs in plasma

    NARCIS (Netherlands)

    Roseboom, H.; Hulshoff, A.

    1979-01-01

    A rapid and simple clean-up and derivatization procedure that can be generally applied to the gas chromatographie (GC) determination of acidic drugs of various chemical and therapeutic classes is described. The drugs are extracted from acidified plasma with chloroform containing 5% of isopropanol,

  2. A RAPID THIN-LAYER CHROMATOGRAPHIC PROCEDURE TO IDENTIFY POOR AND EXTENSIVE OXIDATIVE DRUG METABOLIZERS IN MAN USING DEXTROMETHORPHAN

    NARCIS (Netherlands)

    DEZEEUW, RA; EIKEMA, D; FRANKE, JP; JONKMAN, JHG

    A rapid TLC method is presented to distinguish poor oxidative drug metabolizers from extensive oxidative drug metabolizers. Dextromethorphan (1) is used as test probe because it is safe, well characterized, generally available and easy to measure. The method is based on the extraction of 1 and its

  3. Drug Susceptibility Testing of 31 Antimicrobial Agents on Rapidly Growing Mycobacteria Isolates from China.

    Science.gov (United States)

    Pang, Hui; Li, Guilian; Zhao, Xiuqin; Liu, Haican; Wan, Kanglin; Yu, Ping

    2015-01-01

    Several species of rapidly growing mycobacteria (RGM) are now recognized as human pathogens. However, limited data on effective drug treatments against these organisms exists. Here, we describe the species distribution and drug susceptibility profiles of RGM clinical isolates collected from four southern Chinese provinces from January 2005 to December 2012. Clinical isolates (73) were subjected to in vitro testing with 31 antimicrobial agents using the cation-adjusted Mueller-Hinton broth microdilution method. The isolates included 55 M. abscessus, 11 M. fortuitum, 3 M. chelonae, 2 M. neoaurum, and 2 M. septicum isolates. M. abscessus (75.34%) and M. fortuitum (15.07%), the most common species, exhibited greater antibiotic resistance than the other three species. The isolates had low resistance to amikacin, linezolid, and tigecycline, and high resistance to first-line antituberculous agents, amoxicillin-clavulanic acid, rifapentine, dapsone, thioacetazone, and pasiniazid. M. abscessus and M. fortuitum were highly resistant to ofloxacin and rifabutin, respectively. The isolates showed moderate resistance to the other antimicrobial agents. Our results suggest that tigecycline, linezolid, clofazimine, and cefmetazole are appropriate choices for M. abscessus infections. Capreomycin, sulfamethoxazole, tigecycline, clofazimine, and cefmetazole are potentially good choices for M. fortuitum infections. Our drug susceptibility data should be useful to clinicians.

  4. Drug Susceptibility Testing of 31 Antimicrobial Agents on Rapidly Growing Mycobacteria Isolates from China

    Directory of Open Access Journals (Sweden)

    Hui Pang

    2015-01-01

    Full Text Available Objectives. Several species of rapidly growing mycobacteria (RGM are now recognized as human pathogens. However, limited data on effective drug treatments against these organisms exists. Here, we describe the species distribution and drug susceptibility profiles of RGM clinical isolates collected from four southern Chinese provinces from January 2005 to December 2012. Methods. Clinical isolates (73 were subjected to in vitro testing with 31 antimicrobial agents using the cation-adjusted Mueller-Hinton broth microdilution method. The isolates included 55 M. abscessus, 11 M. fortuitum, 3 M. chelonae, 2 M. neoaurum, and 2 M. septicum isolates. Results. M. abscessus (75.34% and M. fortuitum (15.07%, the most common species, exhibited greater antibiotic resistance than the other three species. The isolates had low resistance to amikacin, linezolid, and tigecycline, and high resistance to first-line antituberculous agents, amoxicillin-clavulanic acid, rifapentine, dapsone, thioacetazone, and pasiniazid. M. abscessus and M. fortuitum were highly resistant to ofloxacin and rifabutin, respectively. The isolates showed moderate resistance to the other antimicrobial agents. Conclusions. Our results suggest that tigecycline, linezolid, clofazimine, and cefmetazole are appropriate choices for M. abscessus infections. Capreomycin, sulfamethoxazole, tigecycline, clofazimine, and cefmetazole are potentially good choices for M. fortuitum infections. Our drug susceptibility data should be useful to clinicians.

  5. 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.

  6. Platform for Rapid Delivery of Biologics and Drugs to Ocular Cells and Tissues Following Combat Associated Trauma

    Science.gov (United States)

    2013-09-01

    death pathways such as apoptosis subsequent to acute trauma as soon as possible, ideally by self- administration of a drug or a biologic that can be... Drugs to Ocular Tissues Including Retina and Cornea . Mol Ther, 2007;16(1):107- 14. 3. Read SP, Cashman SM, and Kumar-Singh R: POD...1 AD_________________ Award Number: W81XWH-12-1-0374 TITLE: Platform for Rapid Delivery of Biologics and Drugs to Ocular Cells

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

    African Journals Online (AJOL)

    M.A. Khanday

    2014-11-25

    Nov 25, 2014 ... Abstract Background: The delivery of drugs through dermal layers known as transdermal ... number of factors which includes the physio-co-chemical prop- ..... 9. Kumari B, Adlakha N. One dimensional model to study the effect.

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

    African Journals Online (AJOL)

    M.A. Khanday

    2014-11-25

    Nov 25, 2014 ... ematical transport models describing the release of drug from various delivery systems and ... numerical simulations to describe the pharmacokinetics of ... studied the diffusion of heat and mass in biological tissues particularly ...

  9. In vivo evaluation of thiolated poly(acrylic acid) as a drug absorption modulator for MRP2 efflux pump substrates.

    Science.gov (United States)

    Greindl, Melanie; Föger, Florian; Hombach, Juliane; Bernkop-Schnürch, Andreas

    2009-08-01

    Recently, several polymers have been reported to modulate drug absorption by inhibition of intestinal efflux pumps such as multidrug resistance proteins (MRPs) and P-glycoprotein (P-gp). The aim of the present study was to evaluate the efficiency of thiolated poly(acrylic acid) (PAA-Cys) to act as a drug absorption modulator for MRP2 efflux pump substrates in vivo, using sulforhodamine 101 as representative MRP2 substrate. In vitro, the permeation-enhancing effect of unmodified PAA and PAA(250)-Cys(,) displaying 580 micromol free thiol groups per gram polymer, was evaluated by using freshly excised rat intestinal mucosa mounted in Ussing-type chambers. In comparison to that of the buffer control, the sulforhodamine 101 transport in the presence of 0.5% unmodified PAA(250) and 0.5% (w/v) PAA(250)-Cys was 1.3- and 4.0-fold improved, respectively. In vivo, sulforhodamine 101 solutions containing 4% (w/v) unmodified PAA(250) or 4% (w/v) thiolated PAA(250) were orally given to rats. The PAA(250)-Cys solution increased the area under the plasma concentration-time curve (AUC(0-12)) of sulforhodamine 101 3.8-fold in comparison to control and 2.2-fold in comparison to unmodified PAA(250). This in vivo study revealed that PAA(250)-Cys significantly increased the oral bioavailability of MRP2 substrate sulforhodamine 101.

  10. 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.

  11. NIR responsive liposomal system for rapid release of drugs in cancer therapy

    Directory of Open Access Journals (Sweden)

    Chen MM

    2017-06-01

    Full Text Available Ming-Mao Chen,1 Yuan-Yuan Liu,1 Guang-Hao Su,2 Fei-Fei Song,1 Yan Liu,3 Qi-Qing Zhang1,4 1Institute of Biomedical and Pharmaceutical Technology, Fuzhou University, Fuzhou, 2Institute of Pediatric Research, Children’s Hospital of Soochow University, Suzhou, 3State Key Lab of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, 4Key Laboratory of Biomedical Material of Tianjin, Institute of Biomedical Engineering, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, People’s Republic of China Abstract: To design a rapid release liposomal system for cancer therapy, a NIR responsive bubble-generating thermosensitive liposome (BTSL system combined with photothermal agent (Cypate, doxorubicin (DOX, and NH4HCO3 was developed. Cypate/DOX-BTSL exhibited a good aqueous stability, photostability, and photothermal effect. In vitro release suggested that the amounts of DOX released from BTSL were obviously higher than that of (NH42SO4 liposomes at 42°C. After NIR irradiation, the hyperthermic temperature induced by Cypate led to the decomposition of NH4HCO3 and the generation of a large number of CO2 bubbles, triggering a rapid release of drugs. Confocal laser scanning microscope and acridine orange staining indicated that Cypate/DOX-BTSL upon irradiation could facilitate to disrupt the lysosomal membranes and realize endolysosomal escape into cytosol, improving the intracellular uptake of DOX clearly. MTT and trypan blue staining implied that the cell damage of Cypate/DOX-BTSL with NIR irradiation was more severe than that in the groups without irradiation. In vivo results indicated that Cypate/DOX-BTSL with irradiation could dramatically increase the accumulation of DOX in tumor, inhibit tumor growth, and reduce systemic side effects of DOX. These data demonstrated that Cypate/DOX-BTSL has the potential to be used as a NIR responsive liposomal system for a rapid

  12. Enhancement of in-vitro drug dissolution of ketoconazole for its optimal in-vivo absorption using Nanoparticles and Solid Dispersion forms of the drug

    Science.gov (United States)

    Syed, Mohammed Irfan

    was modified to include 0.02%, 0.05% and 0.1% sodium lauryl sulfate. Here, after 2 hours, the amount of drug dissolved was calculated to be 10% from controls, 21% from solid dispersion and 36% from nanoparticles in SIF with 0.02% SLS. Drug release was 20% from controls, 41% from solid dispersion and 52% from nanoparticle formulation in SIF with 0.05% SLS. Whereas amount of drug released in SIF with 0.1% SLS showed 21% from the control, 62% from solid dispersion and 85% from Nanoparticles respectively. This data supports that the ketoconazole Nanoparticles and its solid-dispersion exhibit many fold increase in dissolution of the drug, which could lead to a less variable and enhanced in-vivo drug absorption profiles. In addition, the data from the Physical Characterization (DSC, XRD and FTIR) supports that there were no interaction within the ingredients occurred in Nanoparticles and solid-dispersion formulations of the drug sample. Wet Bead Milling and Hot Melt methods proved useful in developing the Nanoparticles and solid dispersion form of ketoconazole. Results from particle size analysis were in correlation with data obtained from Scanning electron Microscopy and size of the nanoparticles was below 100nm. The dissolution studies with the modified simulated intestinal fluid (SIF) exhibited several fold increase in the dissolution of the drug compared to the pure drug powder and the commercial products used as the control. Also, the results from the physical characterization studies clearly support the stability of ketoconazole in both of these formulations.

  13. MRP2 mediated drug-drug interaction: indomethacin increases sulfasalazine absorption in the small intestine, potentially decreasing its colonic targeting.

    Science.gov (United States)

    Dahan, Arik; Amidon, Gordon L

    2010-02-15

    We have recently shown that efflux transport, mediated by multidrug resistance-associated protein 2 (MRP2) and breast cancer resistance protein (BCRP), is responsible for sulfasalazine low-permeability in the small intestine, thereby enabling its colonic targeting and therapeutic action. The purpose of the present study was to evaluate the potential pharmacokinetic interaction between indomethacin and sulfasalazine, in the mechanism of efflux transporter competition. The concentration-dependent effects of indomethacin on sulfasalazine intestinal epithelial transport were investigated across Caco-2 cell monolayers, in both apical to basolateral (AP-BL) and BL-AP directions. The interaction was then investigated in the in situ single-pass rat jejunal perfusion model. Sulfasalazine displayed 30-fold higher BL-AP than AP-BL Caco-2 permeability, indicative of net mucosal secretion. Indomethacin significantly increased AP-BL and decreased BL-AP sulfasalazine Caco-2 transport, in a concentration-dependent manner, with IC(50) values of 75 and 196 microM respectively. In the rat model, higher sulfasalazine concentrations resulted in higher intestinal permeability, consistent with saturation of efflux transporter. Without indomethacin, sulfasalazine demonstrated low rat jejunal permeability (vs. metoprolol). Indomethacin significantly increased sulfasalazine P(eff), effectively shifting it from BCS (biopharmaceutics classification system) Class IV to II. In conclusion, the data indicate that concomitant intake of indomethacin and sulfasalazine may lead to increased absorption of sulfasalazine in the small intestine, thereby reducing its colonic concentration and potentially altering its therapeutic effect. Copyright 2009 Elsevier B.V. All rights reserved.

  14. 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

    Bone tissue engineering implants with sustained local drug delivery provide an opportunity for better postoperative care for bone tumor patients because these implants offer sustained drug release at the tumor site and reduce systemic side effects. A rapid prototyped macroporous polycaprolactone......, this scaffold can fulfill the requirements for both bone tissue engineering and local sustained release of an anticancer drug in vitro. These results suggest that the scaffold can be used clinically in reconstructive surgery after bone tumor resection. Moreover, by changing the composition and amount...... of individual components, the scaffold can find application in other tissue engineering areas that need local sustained release of drug....

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

    African Journals Online (AJOL)

    Non-injection drug use (mainly cannabis, methaqualone, crack cocaine and crystal methamphetamine) and injection drug use (mainly heroin) was occurring in these cities. Drug users report selling sex for money to buy drugs, and CSWs used drugs before, during and after sex. Most (70%) of the drug-using KIs offered HIV ...

  16. Sequential determination of arsenic, selenium, antimony, and tellurium in foods via rapid hydride evolution and atomic absorption spectrometry

    International Nuclear Information System (INIS)

    Fiorino, J.A.; Jones, J.W.; Capar, S.G.

    1976-01-01

    Analysis of acid digests of foods for As, Se, Sb, and Te was semiautomated. Hydrides generated by controlled addition of base stabilized NaBH 4 solution to acid digests are transported directly into a shielded, hydrogen (nitrogen diluted), entrained-air flame for atomic absorption spectrophotometric determination of the individual elements. The detection limits, based on 1 g of digested sample, are approximately 10 to 20 ng/g for all four elements. Measurement precision is 1 to 2 percent relative standard deviation for each element measured at 0.10 μg. A comparison is made of results of analysis of lyophilized fish tissues for As and Se by instrumental neutron activation (INAA), hydride generation with atomic absorption spectrometry, fluorometry, and spectrophotometry. NBS standard reference materials (orchard leaves and bovine liver) analyzed for As, Se, and Sb by this method show excellent agreement with certified values and with independent NAA values

  17. Impact of concentration and rate of intraluminal drug delivery on absorption and gut wall metabolism of verapamil in humans.

    Science.gov (United States)

    Glaeser, Hartmut; Drescher, Siegfried; Hofmann, Ute; Heinkele, Georg; Somogyi, Andrew A; Eichelbaum, Michel; Fromm, Martin F

    2004-09-01

    In humans gut wall metabolism can be quantitatively as important as hepatic drug metabolism in limiting the systemic exposure to drugs after oral administration. However, it has been proposed that the role of gut wall metabolism might be overemphasized, because high luminal drug concentrations would lead to a saturation of gut wall metabolism. Therefore we investigated the impact of concentration and rate of intraluminal drug delivery on absorption (F(abs)) and gastrointestinal extraction (E(GI)) of a luminally administered cytochrome P450 (CYP) 3A4 substrate (verapamil) using a multilumen perfusion catheter in combination with a stable isotope technique. Two 20-cm-long, adjacent jejunal segments were isolated with the multilumen perfusion catheter in 7 subjects. In this study 80 mg of unlabeled verapamil (d0-verapamil 15 min) was infused into one segment over a 15-minute period, 80 mg of 3-fold deuterated verapamil (d3-verapamil 240 min) was administered over a 240-minute period into the other segment, and simultaneously, 5 mg of 7-fold deuterated verapamil (d7-verapamil) was injected intravenously over a 15-minute period. The rate of intraluminal drug delivery had only a modest effect on bioavailability of the verapamil isotopes (after correction for F abs ) (F/F abs d3-verapamil 240 min versus d0-verapamil 15 min, 0.24 +/- 0.10 versus 0.20 +/- 0.09; P d3-verapamil 240 min was 0.50 +/- 0.18 compared with 0.59 +/- 0.14 for d0 -verapamil 15 min ( P d0-verapamil 15 min ) correlated strongly with E GI (d3-verapamil 240 min ) (r = 0.94, P d0-verapamil 15 min /d3-verapamil 240 min (r = 0.62, P =.03). Substantial gut wall metabolism of verapamil occurs in humans and can be predicted from ex vivo data by use of shed enterocytes. The different intraluminal concentrations and rates of intraluminal drug delivery did not lead to a pronounced saturation of intestinal drug metabolism.

  18. Microbiome-mediated bile acid modification: Role in intestinal drug absorption and metabolism.

    Science.gov (United States)

    Enright, Elaine F; Griffin, Brendan T; Gahan, Cormac G M; Joyce, Susan A

    2018-04-13

    Once regarded obscure and underappreciated, the gut microbiota (the microbial communities colonizing the gastrointestinal tract) is gaining recognition as an influencer of many aspects of human health. Also increasingly apparent is the breadth of interindividual variation in these co-evolved microbial-gut associations, presenting novel quests to explore implications for disease and therapeutic response. In this respect, the unearthing of the drug-metabolizing capacity of the microbiota has provided impetus for the integration of microbiological and pharmacological research. This review considers a potential mechanism, 'microbial bile acid metabolism', by which the intricate interplay between the host and gut bacteria may influence drug pharmacokinetics. Bile salts traditionally regarded as biological surfactants, synthesized by the host and biotransformed by gut bacteria, are now also recognized as signalling molecules that affect diverse physiological processes. Accumulating data indicate that bile salts are not equivalent with respect to their physicochemical properties, micellar solubilization capacities for poorly water-soluble drugs, crystallization inhibition tendencies nor potencies for bile acid receptor activation. Herein, the origin, physicochemical properties, physiological functions, plasticity and pharmaceutical significance of the human bile acid pool are discussed. Microbial dependant differences in the composition of the human bile acid pool, simulated intestinal media and commonly used preclinical species is highlighted to better understand in vivo performance predictiveness. While the precise impact of an altered gut microbiome, and consequently bile acid pool, in the biopharmaceutical setting remains largely elusive, the objective of this article is to aid knowledge acquisition through a detailed review of the literature. Copyright © 2018 Elsevier Ltd. All rights reserved.

  19. Rapid food decomposition by H2O2-H2SO4 for determination of total mercury by flow injection cold vapor atomic absorption spectrometry.

    Science.gov (United States)

    Zenebon, Odair; Sakuma, Alice M; Dovidauskas, Sergio; Okada, Isaura A; de, MaioFrancaD; Lichtig, Jaim

    2002-01-01

    A mixture of 50% H2O2-H2SO4 (3 + 1, v/v) was used for decomposition of food in open vessels at 80 degrees C. The treatment allowed rapid total mercury determination by flow injection cold vapor atomic absorption spectrometry. Cabbage, potatoes, peanuts paste, hazelnuts paste, oats, tomatoes and their derivatives, oysters, shrimps, prawns, shellfish, marine algae, and many kinds of fish were analyzed by the proposed methodology with a limit of quantitation of 0.86 +/- 0.08 microg/L mercury in the final solution. Reference materials tested also gave excellent recovery.

  20. 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.

  1. Understanding the Oral Mucosal Absorption and Resulting Clinical Pharmacokinetics of Asenapine

    NARCIS (Netherlands)

    Bartlett, Jeremy A.; Maarschalk, Kees van der Voort

    2012-01-01

    Absorption of drugs from the oral cavity into the mucosal tissues is typically a fast event. Dissolved drugs partition into the mucosal membranes and within minutes will reach equilibrium with drug in solution in the oral cavity. However, this does not always equate to rapid drug appearance in the

  2. Microneedles as Enhancer of Drug Absorption Through the Skin and Applications in Medicine and Cosmetology.

    Science.gov (United States)

    Serrano-Castañeda, Pablo; Escobar-Chavez, Jose Juan; Rodriguez-Cruz, Isabel Marlen; Melgoza, Luz Maria; Martinez-Hernandez, Jessica

    2018-01-01

    The microneedles technology has found applications in many health-related fields. For example, their application in drugs and vaccines delivery as well, as the determination of biomarkers, has been reported. They also have a place in the dermatology and cosmetic areas such as the treatment of wounds from burns, scars, acne, depigmentation, and alopecia will be shown. Microneedles are used in therapeutic applications and are manufactured using materials such as metal (steel, titanium, nickel), polymer (oly-glycolic acid (PGA), poly-lactide-co-glycolide acid (PLGA), poly-L-lactic acid (PLA), chitosan), glass, silicon, ceramic, carbohydrates (trehalose, sucrose, mannitol). Examples of application of microneedles and their advantages and disadvantages are discussed. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

  3. Correlation between octanol/water and liposome/water distribution coefficients and drug absorption of a set of pharmacologically active compounds.

    Science.gov (United States)

    Esteves, Freddy; Moutinho, Carla; Matos, Carla

    2013-06-01

    Absorption and consequent therapeutic action are key issues in the development of new drugs by the pharmaceutical industry. In this sense, different models can be used to simulate biological membranes to predict the absorption of a drug. This work compared the octanol/water and the liposome/water models. The parameters used to relate the two models were the distribution coefficients between liposomes and water and octanol and water and the fraction of drug orally absorbed. For this study, 66 drugs were collected from literature sources and divided into four groups according to charge and ionization degree: neutral; positively charged; negatively charged; and partially ionized/zwitterionic. The results show a satisfactory linear correlation between the octanol and liposome systems for the neutral (R²= 0.9324) and partially ionized compounds (R²= 0.9367), contrary to the positive (R²= 0.4684) and negatively charged compounds (R²= 0.1487). In the case of neutral drugs, results were similar in both models because of the high fraction orally absorbed. However, for the charged drugs (positively, negatively, and partially ionized/zwitterionic), the liposomal model has a more-appropriate correlation with absorption than the octanol model. These results show that the neutral compounds only interact with membranes through hydrophobic bonds, whereas charged drugs favor electrostatic interactions established with the liposomes. With this work, we concluded that liposomes may be a more-appropriate biomembrane model than octanol for charged compounds.

  4. 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.

  5. A rapid situation assessment (RSA) study of alcohol and drug use in Lebanon.

    Science.gov (United States)

    Karam, Elie G; Ghandour, Lilian A; Maalouf, Wadih E; Yamout, Karim; Salamoun, Mariana M

    2010-01-01

    Research on substance use and misuse in Lebanon is scarce and, when available, focuses on a specific substance or a limited segment of the population. The objective of this Rapid Situation Assessment (RAS) study was to survey the use of multiple substances in diverse segments of the Lebanese population. A multi-method and multi-sample survey was conducted to collect quantitative and qualitative data from the academic sector (high school and university students), substance users in treatment or under arrest (prison, detention), and non-institutionalized "street" users. Age of first use of substances started as early as 9 years in the youth sample. Moreover, 12% of the high school students reported smoking one or more packs of cigarettes per day and 9% of the university students met criteria for DSM-IV alcohol abuse. Cannabis represented the most commonly used illicit drug in both high school and university students, and tranquilizers were the most frequently misused medicinal substance. Heroin was responsible for 50% of the treatment admissions, followed by cocaine (20%), and alcohol (20%); heroin was also the most common substance of arrest. Recidivism was almost the rule for heroin users across all treatment settings. Unperceived need for treatment was the most common reason for not seeking treatment in non-institutionalized drug users (47.6%). Injecting drug use was a common behavior noted within substance using populations, in treatment and non-institutionalized (about 50% of them), with a high rate of needle sharing practices. About half of all patients in treatment had a history of police arrests, and about one-third of those in prison ever received prior treatment for substance use. The study points towards a growing trend for substance use problems in early adolescence that warrants close monitoring. Further investigation of these patterns is needed since the Lebanese population might have specific pathways of abuse. There is a need to bring together various

  6. Drug Delivery and Transport into the Central Circulation: An Example of Zero-Order In vivo Absorption of Rotigotine from a Transdermal Patch Formulation.

    Science.gov (United States)

    Cawello, Willi; Braun, Marina; Andreas, Jens-Otto

    2018-01-13

    Pharmacokinetic studies using deconvolution methods and non-compartmental analysis to model clinical absorption of drugs are not well represented in the literature. The purpose of this research was (1) to define the system of equations for description of rotigotine (a dopamine receptor agonist delivered via a transdermal patch) absorption based on a pharmacokinetic model and (2) to describe the kinetics of rotigotine disposition after single and multiple dosing. The kinetics of drug disposition was evaluated based on rotigotine plasma concentration data from three phase 1 trials. In two trials, rotigotine was administered via a single patch over 24 h in healthy subjects. In a third trial, rotigotine was administered once daily over 1 month in subjects with early-stage Parkinson's disease (PD). A pharmacokinetic model utilizing deconvolution methods was developed to describe the relationship between drug release from the patch and plasma concentrations. Plasma-concentration over time profiles were modeled based on a one-compartment model with a time lag, a zero-order input (describing a constant absorption via skin into central circulation) and first-order elimination. Corresponding mathematical models for single- and multiple-dose administration were developed. After single-dose administration of rotigotine patches (using 2, 4 or 8 mg/day) in healthy subjects, a constant in vivo absorption was present after a minor time lag (2-3 h). On days 27 and 30 of the multiple-dose study in patients with PD, absorption was constant during patch-on periods and resembled zero-order kinetics. Deconvolution based on rotigotine pharmacokinetic profiles after single- or multiple-dose administration of the once-daily patch demonstrated that in vivo absorption of rotigotine showed constant input through the skin into the central circulation (resembling zero-order kinetics). Continuous absorption through the skin is a basis for stable drug exposure.

  7. Identifying rapidly parasiticidal anti-malarial drugs using a simple and reliable in vitro parasite viability fast assay.

    Science.gov (United States)

    Linares, María; Viera, Sara; Crespo, Benigno; Franco, Virginia; Gómez-Lorenzo, María G; Jiménez-Díaz, María Belén; Angulo-Barturen, Íñigo; Sanz, Laura María; Gamo, Francisco-Javier

    2015-11-05

    The emergence of Plasmodium falciparum resistance to artemisinins threatens to undermine the effectiveness of artemisinin-based combination anti-malarial therapy. Developing suitable drugs to replace artemisinins requires the identification of new compounds that display rapid parasite killing kinetics. However, no current methods fully meet the requirements to screen large compound libraries for candidates with such properties. This study describes the development and validation of an in vitro parasite viability fast assay for identifying rapidly parasiticidal anti-malarial drugs. Parasite killing kinetics were determined by first culturing unlabelled erythrocytes with P. falciparum in the presence of anti-malarial drugs for 24 or 48 h. After removing the drug, samples were added to erythrocytes pre-labelled with intracellular dye to allow their subsequent identification. The ability of viable parasites to re-establish infection in labelled erythrocytes could then be detected by two-colour flow cytometry after tagging of parasite DNA. Thus, double-stained erythrocytes (with the pre-labelled intracellular dye and the parasite DNA dye) result only after establishment of new infections by surviving parasites. The capacity of the test anti-malarial drugs to eliminate viable parasites within 24 or 48 h could, therefore, be determined. The parasite viability fast assay could be completed within 48 h following drug treatment and distinguished between rapidly parasiticidal anti-malarial drugs versus those acting more slowly. The assay was validated against ten standard anti-malarial agents with known properties and results correlated well with established methods. An abbreviated assay, suitable for adaption to medium-high throughput screening, was validated and applied against a set of 20 compounds retrieved from the publically available Medicines for Malaria Venture 'Malaria Box'. The quantification of new infections to determine parasite viability offers important

  8. 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.

  9. Iron absorption studies

    International Nuclear Information System (INIS)

    Ekenved, G.

    1976-01-01

    The main objective of the present work was to study iron absorption from different iron preparations in different types of subjects and under varying therapeutic conditions. The studies were performed with different radioiron isotope techniques and with a serum iron technique. The preparations used were solutions of ferrous sulphate and rapidly-disintegrating tablets containing ferrous sulphate, ferrous fumarate and ferrous carbonate and a slow-release ferrous sulphate tablet of an insoluble matrix type (Duroferon Durules). The serum iron method was evaluated and good correlation was found between the serum iron response and the total amount of iron absorbed after an oral dose of iron given in solution or in tablet form. New technique for studying the in-vivo release properties of tablets was presented. Iron tablets labelled with a radio-isotope were given to healthy subjects. The decline of the radioactivity in the tablets was followed by a profile scanning technique applied to different types of iron tablets. The release of iron from the two types of tablets was shown to be slower in vivo than in vitro. It was found that co-administration of antacids and iron tablets led to a marked reduction in the iron absorption and that these drugs should not be administered sumultaneously. A standardized meal markedly decreased the absorbability of iron from iron tablets. The influence of the meal was more marked with rapidly-disintegrating than with slow-release ferrous sulphate tablets. The absorption from rapidly-disintegrating and slow-release ferrous sulphate tablets was compared under practical clinical conditions during an extended treatment period. The studies were performed in healthy subjects, blood donors and patients with iron deficiency anaemia and it was found that the absorption of iron from the slow-release tablets was significantly better than from the rapidly-disintegrating tablets in all three groups of subjects. (author)

  10. High-Throughput Lipolysis in 96-Well Plates for Rapid Screening of Lipid-Based Drug Delivery Systems

    DEFF Research Database (Denmark)

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

    2017-01-01

    The high-throughput in vitro intestinal lipolysis model (HTP) applicable for rapid and low-scale screening of lipid-based drug delivery systems (LbDDSs) was optimized and adjusted as to be conducted in 96-well plates (HTP-96). Three different LbDDSs (I-III) loaded with danazol or cinnarizine were...

  11. Rapid Determination of Trace Palladium in Active Pharmaceutical Ingredients by Magnetic Solid-Phase Extraction and Flame Atomic Absorption Spectrometry

    Science.gov (United States)

    Yin, Q. H.; Zhu, D. M.; Yang, D. Z.; Hu, Q. F.; Yang, Y. L.

    2018-01-01

    Clutaraldehyde cross-linked magnetic chitosan nanoparticles were synthesized and used as an adsorbent for the dispersive solid-phase extraction of palladium in active pharmaceutical ingredients (APIs) prior to analysis by a flame atomic absorption spectrophotometer. FT-IR, X-ray diffraction, and TEM were used to characterize the adsorbent. Various parameters of experimental performance, such as adsorbent amount, pH, adsorption time, desorption solutions, coexisting ions, and adsorbent reusability, were investigated and optimized. Under the optimized conditions, good linearity was achieved in the 5.0-500 μg/L concentration range, with correlation coefficients of 0.9989. The limit of detection is 2.8 μg/L and the recoveries of spiked samples ranged from 91.7 to 97.6%. It was confirmed that the GMCNs nanocomposite was a promising adsorbing material for extraction and preconcentration of Pd in APIs.

  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...

  13. Nasal Inserts for Drug Delivery: An Overview

    African Journals Online (AJOL)

    In this review, the benefits, limitations and absorption mechanisms of the nasal route, as well ... molecules including peptide and proteins for ... (Mw) drugs, rapid and fast onset of action due to ... while the former act by disrupting the nasal.

  14. Can a rapid measure of self-exposure to drugs of abuse provide dimensional information on depression comorbidity?

    Science.gov (United States)

    Butelman, Eduardo Roque; Bacciardi, Silvia; Maremmani, Angelo Giovanni Icro; Darst-Campbell, Maya; Correa da Rosa, Joel; Kreek, Mary Jeanne

    2017-09-01

    Addictions to heroin or to cocaine are associated with substantial psychiatric comorbidity, including depression. Poly-drug self-exposure (eg, to heroin, cocaine, cannabis, or alcohol) is also common, and may further affect depression comorbidity. This case-control study examined the relationship of exposure to the above drugs and depression comorbidity. Participants were recruited from methadone maintenance clinics, and from the community. Adult male and female participants (n = 1,201) were ascertained consecutively by experienced licensed clinicians. The instruments used were the SCID-I, and Kreek-McHugh-Schluger-Kellogg (KMSK) scales, which provide a rapid dimensional measure of maximal lifetime self-exposure to each of the above drugs. This measure ranges from no exposure to high unit dose, high frequency, and long duration of exposure. A multiple logistic regression with stepwise variable selection revealed that increasing exposure to heroin or to cocaine was associated greater odds of depression, with all cases and controls combined. In cases with an opioid dependence diagnosis, increasing cocaine exposure was associated with a further increase in odds of depression. However, in cases with a cocaine dependence diagnosis, increasing exposure to either cannabis or alcohol, as well as heroin, was associated with a further increase in odds of depression. This dimensional analysis of exposure to specific drugs provides insights on depression comorbidity with addictive diseases, and the impact of poly-drug exposure. A rapid analysis of exposure to drugs of abuse reveals how specific patterns of drug and poly-drug exposure are associated with increasing odds of depression. This approach detected quantitatively how different patterns of poly-drug exposure can result in increased odds of depression comorbidity, in cases diagnosed with opioid versus cocaine dependence. (Am J Addict 2017;26:632-639). © 2017 American Academy of Addiction Psychiatry.

  15. 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.

  16. 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

  17. 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.

  18. 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.

  19. 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 K a and P eff 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.

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

    Science.gov (United States)

    Chen, Muwan; Le, Dang QS; Hein, San; Li, Pengcheng; Nygaard, Jens V; Kassem, Moustapha; Kjems, Jørgen; Besenbacher, Flemming; Bünger, Cody

    2012-01-01

    Bone tissue engineering implants with sustained local drug delivery provide an opportunity for better postoperative care for bone tumor patients because these implants offer sustained drug release at the tumor site and reduce systemic side effects. A rapid prototyped macroporous polycaprolactone scaffold was embedded with a porous matrix composed of chitosan, nanoclay, and β-tricalcium phosphate by freeze-drying. This composite scaffold was evaluated on its ability to deliver an anthracycline antibiotic and to promote formation of mineralized matrix in vitro. Scanning electronic microscopy, confocal imaging, and DNA quantification confirmed that immortalized human bone marrow-derived mesenchymal stem cells (hMSC-TERT) cultured in the scaffold showed high cell viability and growth, and good cell infiltration to the pores of the scaffold. Alkaline phosphatase activity and osteocalcin staining 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, this scaffold can fulfill the requirements for both bone tissue engineering and local sustained release of an anticancer drug in vitro. These results suggest that the scaffold can be used clinically in reconstructive surgery after bone tumor resection. Moreover, by changing the composition and amount of individual components, the scaffold can find application in other tissue engineering areas that need local sustained release of drug. PMID:22904634

  1. Quantification of the fluorine containing drug 5-fluorouracil in cancer cells by GaF molecular absorption via high-resolution continuum source molecular absorption spectrometry

    International Nuclear Information System (INIS)

    Krüger, Magnus; Huang, Mao-Dong; Becker-Roß, Helmut; Florek, Stefan; Ott, Ingo; Gust, Ronald

    2012-01-01

    The development of high-resolution continuum source molecular absorption spectrometry made the quantification of fluorine feasible by measuring the molecular absorption as gallium monofluoride (GaF). Using this new technique, we developed on the example of 5-fluorouracil (5-FU) a graphite furnace method to quantify fluorine in organic molecules. The effect of 5-FU on the generation of the diatomic GaF molecule was investigated. The experimental conditions such as gallium nitrate amount, temperature program, interfering anions (represented as corresponding acids) and calibration for the determination of 5-FU in standard solution and in cellular matrix samples were investigated and optimized. The sample matrix showed no effect on the sensitivity of GaF molecular absorption. A simple calibration curve using an inorganic sodium fluoride solution can conveniently be used for the calibration. The described method is sensitive and the achievable limit of detection is 0.23 ng of 5-FU. In order to establish the concept of “fluorine as a probe in medicinal chemistry” an exemplary application was selected, in which the developed method was successfully demonstrated by performing cellular uptake studies of the 5-FU in human colon carcinoma cells. - Highlights: ► Development of HR-CS MAS for quantification of fluorine bound to organic molecules ► Measuring as molecular absorption of gallium monofluoride ► Quantification of organic-bound fluorine in biological material ► The concept of “fluorine as a probe in medicinal chemistry” could be established

  2. Quantification of the fluorine containing drug 5-fluorouracil in cancer cells by GaF molecular absorption via high-resolution continuum source molecular absorption spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Krueger, Magnus [Freie Universitaet Berlin, Institut fuer Pharmazie, Pharmazeutische Chemie, Koenigin-Luise-Str. 2-4, 14195 Berlin (Germany); Huang, Mao-Dong; Becker-Ross, Helmut; Florek, Stefan [Leibniz Institut fuer Analytische Wissenschaften, ISAS-e.V., Department Berlin, Albert-Einstein-Str. 9, 12489 Berlin (Germany); Ott, Ingo [Technische Universitaet Carolo Wilhelmina zu Braunschweig, Institut fuer Medizinische und Pharmazeutische Chemie, Beethovenstr. 55, 38106 Braunschweig (Germany); Gust, Ronald, E-mail: ronald.gust@uibk.ac.at [Universitaet Innsbruck, Institut fuer Pharmazie, Pharmazeutische Chemie, Innrain 80/82, 6020 Innsbruck (Austria)

    2012-03-15

    The development of high-resolution continuum source molecular absorption spectrometry made the quantification of fluorine feasible by measuring the molecular absorption as gallium monofluoride (GaF). Using this new technique, we developed on the example of 5-fluorouracil (5-FU) a graphite furnace method to quantify fluorine in organic molecules. The effect of 5-FU on the generation of the diatomic GaF molecule was investigated. The experimental conditions such as gallium nitrate amount, temperature program, interfering anions (represented as corresponding acids) and calibration for the determination of 5-FU in standard solution and in cellular matrix samples were investigated and optimized. The sample matrix showed no effect on the sensitivity of GaF molecular absorption. A simple calibration curve using an inorganic sodium fluoride solution can conveniently be used for the calibration. The described method is sensitive and the achievable limit of detection is 0.23 ng of 5-FU. In order to establish the concept of 'fluorine as a probe in medicinal chemistry' an exemplary application was selected, in which the developed method was successfully demonstrated by performing cellular uptake studies of the 5-FU in human colon carcinoma cells. - Highlights: Black-Right-Pointing-Pointer Development of HR-CS MAS for quantification of fluorine bound to organic molecules Black-Right-Pointing-Pointer Measuring as molecular absorption of gallium monofluoride Black-Right-Pointing-Pointer Quantification of organic-bound fluorine in biological material Black-Right-Pointing-Pointer The concept of 'fluorine as a probe in medicinal chemistry' could be established.

  3. [Effect of Food Thickeners on the Disintegration, Dissolution, and Drug Activity of Rapid Oral-disintegrating Tablets].

    Science.gov (United States)

    Tomita, Takashi; Kohda, Yukinao; Kudo, Kenzo

    2018-01-01

     For patients with dysphagia in medical facilities and nursing homes, food thickeners are routinely used to aid the ingestion of medicines such as tablets. However, some types of thickeners affect the disintegration and dissolution of tablets, such as rapidly-disintegrating magnesium oxide tablets and donepezil hydrochloride orally disintegrating tablets. Additionally, delayed disintegration and dissolution of tablets affect a drug's efficacy. As an example, with Voglibose orally disintegrating tablets, marked differences are observed in changes in glucose levels during glucose tolerance testing. When using food thickeners to aid tablet ingestion, it is therefore necessary to select a product that has little effect on drug disintegration, dissolution, and activity.

  4. 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 (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.

  5. Quantification of the fluorine containing drug 5-fluorouracil in cancer cells by GaF molecular absorption via high-resolution continuum source molecular absorption spectrometry

    Science.gov (United States)

    Krüger, Magnus; Huang, Mao-Dong; Becker-Roß, Helmut; Florek, Stefan; Ott, Ingo; Gust, Ronald

    The development of high-resolution continuum source molecular absorption spectrometry made the quantification of fluorine feasible by measuring the molecular absorption as gallium monofluoride (GaF). Using this new technique, we developed on the example of 5-fluorouracil (5-FU) a graphite furnace method to quantify fluorine in organic molecules. The effect of 5-FU on the generation of the diatomic GaF molecule was investigated. The experimental conditions such as gallium nitrate amount, temperature program, interfering anions (represented as corresponding acids) and calibration for the determination of 5-FU in standard solution and in cellular matrix samples were investigated and optimized. The sample matrix showed no effect on the sensitivity of GaF molecular absorption. A simple calibration curve using an inorganic sodium fluoride solution can conveniently be used for the calibration. The described method is sensitive and the achievable limit of detection is 0.23 ng of 5-FU. In order to establish the concept of "fluorine as a probe in medicinal chemistry" an exemplary application was selected, in which the developed method was successfully demonstrated by performing cellular uptake studies of the 5-FU in human colon carcinoma cells.

  6. 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.

  7. Rapid, radiolabeled-microculture method that uses macrophages for in vitro evaluation of Mycobacterium leprae viability and drug susceptibility.

    Science.gov (United States)

    Mittal, A; Sathish, M; Seshadri, P S; Nath, I

    1983-04-01

    This paper describes a microculture rapid assay using radiolabeling and mouse macrophages to determine the viability and the drug susceptibility or resistance of Mycobacterium leprae. Comparison of M. leprae resident macrophage cultures maintained in 96-well flat-bottomed plates showed results for viability and susceptibility or resistance to dapsone that were similar to results for concurrent cultures in Leighton tubes with greater numbers of bacilli and macrophages.

  8. Rapid, Radiolabeled-Microculture Method That Uses Macrophages for In Vitro Evaluation of Mycobacterium leprae Viability and Drug Susceptibility

    OpenAIRE

    Mittal, A.; Sathish, M.; Seshadri, P. S.; Nath, Indira

    1983-01-01

    This paper describes a microculture rapid assay using radiolabeling and mouse macrophages to determine the viability and the drug susceptibility or resistance of Mycobacterium leprae. Comparison of M. leprae resident macrophage cultures maintained in 96-well flat-bottomed plates showed results for viability and susceptibility or resistance to dapsone that were similar to results for concurrent cultures in Leighton tubes with greater numbers of bacilli and macrophages.

  9. 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.

  10. 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.

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

    Science.gov (United States)

    Gupta, Himanshu R; Patil, Yogesh; Singh, Dipty; Thakur, Mansee

    2016-12-01

    model is recommended as a well-established method for rapidly assessing the toxicity of homeopathic drugs.

  12. 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.

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

    Directory of Open Access Journals (Sweden)

    Chen M

    2012-08-01

    Full Text Available Muwan Chen,1,2 Dang QS Le,1,2 San Hein,2 Pengcheng Li,1 Jens V Nygaard,2 Moustapha Kassem,3 Jørgen Kjems,2 Flemming Besenbacher,2 Cody Bünger11Orthopaedic Research Lab, Aarhus University Hospital, Aarhus C, Denmark; 2Interdisciplinary Nanoscience Center (iNANO, Aarhus University, Aarhus C, Denmark; 3Department of Endocrinology and Metabolism, Odense University Hospital, Odense C, DenmarkAbstract: Bone tissue engineering implants with sustained local drug delivery provide an opportunity for better postoperative care for bone tumor patients because these implants offer sustained drug release at the tumor site and reduce systemic side effects. A rapid prototyped macroporous polycaprolactone scaffold was embedded with a porous matrix composed of chitosan, nanoclay, and β-tricalcium phosphate by freeze-drying. This composite scaffold was evaluated on its ability to deliver an anthracycline antibiotic and to promote formation of mineralized matrix in vitro. Scanning electronic microscopy, confocal imaging, and DNA quantification confirmed that immortalized human bone marrow-derived mesenchymal stem cells (hMSC-TERT cultured in the scaffold showed high cell viability and growth, and good cell infiltration to the pores of the scaffold. Alkaline phosphatase activity and osteocalcin staining 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, this scaffold can fulfill the requirements for both bone tissue engineering and local sustained release of an anticancer drug in vitro. These results suggest that the scaffold can be used clinically in reconstructive surgery after bone tumor resection. Moreover, by changing the composition and amount of individual components, the scaffold can find application in other

  14. A rapid approach for characterization of thiol-conjugated antibody-drug conjugates and calculation of drug-antibody ratio by liquid chromatography mass spectrometry.

    Science.gov (United States)

    Firth, David; Bell, Leonard; Squires, Martin; Estdale, Sian; McKee, Colin

    2015-09-15

    We present the demonstration of a rapid "middle-up" liquid chromatography mass spectrometry (LC-MS)-based workflow for use in the characterization of thiol-conjugated maleimidocaproyl-monomethyl auristatin F (mcMMAF) and valine-citrulline-monomethyl auristatin E (vcMMAE) antibody-drug conjugates. Deconvoluted spectra were generated following a combination of deglycosylation, IdeS (immunoglobulin-degrading enzyme from Streptococcus pyogenes) digestion, and reduction steps that provide a visual representation of the product for rapid lot-to-lot comparison-a means to quickly assess the integrity of the antibody structure and the applied conjugation chemistry by mass. The relative abundance of the detected ions also offer information regarding differences in drug conjugation levels between samples, and the average drug-antibody ratio can be calculated. The approach requires little material (<100 μg) and, thus, is amenable to small-scale process development testing or as an early component of a complete characterization project facilitating informed decision making regarding which aspects of a molecule might need to be examined in more detail by orthogonal methodologies. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Impaired drug absorption due to high stomach pH: a review of strategies for mitigation of such effect to enable pharmaceutical product development.

    Science.gov (United States)

    Mitra, Amitava; Kesisoglou, Filippos

    2013-11-04

    Published reports have clearly shown that weakly basic drugs which have low solubility at high pH could have impaired absorption in patients with high gastric pH thus leading to reduced and variable bioavailability. Since such reduction in exposure can lead to significant loss of efficacy, it is imperative to (1) understand the behavior of the compound as a function of stomach pH to inform of any risk of bioavailability loss in clinical studies and (2) develop a robust formulation which can provide adequate exposure in achlorhydric patients. In this review paper, we provide an overview of the factors that can cause high gastric pH in human, discuss clinical and preclinical pharmacokinetic data for weak bases under conditions of normal and high gastric pH, and give examples of formulation strategies to minimize or mitigate the reduced absorption of weakly basic drugs under high gastric pH conditions. It should be noted that the ability to overcome pH sensitivity issues is highly compound dependent and there are no obvious and general solutions to overcome such effect. Further, we discuss, along with several examples, the use of biopharmaceutical tools such as in vitro dissolution, absorption modeling, and gastric pH modified animal models to assess absorption risk of weak bases in high gastric pH and also the use of these tools to enable development of formulations to mitigate such effects.

  16. 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.

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

    KAUST Repository

    Coll, Francesc; McNerney, Ruth; Preston, Mark D; Guerra-Assunç ã o, José Afonso; Warry, Andrew; Hill-Cawthorne, Grant A.; Mallard, Kim; Nair, Mridul; Miranda, Anabela; Alves, Adriana; Perdigã o, Joã o; Viveiros, Miguel; Portugal, Isabel; Hasan, Zahra; Hasan, Rumina; Glynn, Judith R; Martin, Nigel; Pain, Arnab; Clark, Taane G

    2015-01-01

    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

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

    OpenAIRE

    Pelkonen L; Tengvall-Unadike U; Ruponen M; Kidron H; del Amo EM; Reinisalo M; Urtti A

    2017-01-01

    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-...

  19. A new concept of efficient therapeutic drug monitoring using the high-resolution continuum source absorption spectrometry and the surface enhanced Raman spectroscopy

    Science.gov (United States)

    Xing, Yanlong; Fuss, Harald; Lademann, Jürgen; Huang, Mao Dong; Becker-Ross, Helmut; Florek, Stefan; Patzelt, Alexa; Meinke, Martina C.; Jung, Sora; Esser, Norbert

    2018-04-01

    In this study, a new therapeutic drug monitoring approach has been tested based on the combination of CaF molecular absorption using high-resolution continuum source absorption spectrometry (HR-CSAS) and surface enhanced Raman spectroscopy (SERS). HR-CSAS with mini graphite tube was successfully tested for clinical therapeutic drug monitoring of the fluorine-containing drug capecitabine in sweat samples of cancer patients: It showed advantageous features of high selectivity (no interference from Cl), high sensitivity (characteristic mass of 0.1 ng at CaF 583.069 nm), low sample consumption (down to 30 nL) and fast measurement (no sample pretreatment and less than 1 min of responding time) in tracing the fluorine signal out of capecitabine. However, this technique has the disadvantage of the total loss of the drug's structure information after burning the sample at very high temperature. Therefore, a new concept of combining HR-CSAS with a non-destructive spectroscopic method (SERS) was proposed for the sensitive sensing and specific identification of capecitabine. We tested and succeed in obtaining the molecular characteristics of the metabolite of capecitabine (named 5-fluorouracil) by the non-destructive SERS technique. With the results shown in this work, it is demonstrated that the combined spectroscopic technique of HR-CSAS and SERS will be very useful in efficient therapeutic drug monitoring in the future.

  20. 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

  1. Removing the bottleneck in whole genome sequencing of Mycobacterium tuberculosis for rapid drug resistance analysis: a call to action

    Directory of Open Access Journals (Sweden)

    Ruth McNerney

    2017-03-01

    Full Text Available Whole genome sequencing (WGS can provide a comprehensive analysis of Mycobacterium tuberculosis mutations that cause resistance to anti-tuberculosis drugs. With the deployment of bench-top sequencers and rapid analytical software, WGS is poised to become a useful tool to guide treatment. However, direct sequencing from clinical specimens to provide a full drug resistance profile remains a serious challenge. This article reviews current practices for extracting M. tuberculosis DNA and possible solutions for sampling sputum. Techniques under consideration include enzymatic digestion, physical disruption, chemical degradation, detergent solubilization, solvent extraction, ligand-coated magnetic beads, silica columns, and oligonucleotide pull-down baits. Selective amplification of genomic bacterial DNA in sputum prior to WGS may provide a solution, and differential lysis to reduce the levels of contaminating human DNA is also being explored. To remove this bottleneck and accelerate access to WGS for patients with suspected drug-resistant tuberculosis, it is suggested that a coordinated and collaborative approach be taken to more rapidly optimize, compare, and validate methodologies for sequencing from patient samples.

  2. Expression Profile of Drug and Nutrient Absorption Related Genes in Madin-Darby Canine Kidney (MDCK Cells Grown under Differentiation Conditions

    Directory of Open Access Journals (Sweden)

    Balvinder S. Vig

    2012-06-01

    Full Text Available The expression levels of genes involved in drug and nutrient absorption were evaluated in the Madin-Darby Canine Kidney (MDCK in vitro drug absorption model. MDCK cells were grown on plastic surfaces (for 3 days or on Transwell® membranes (for 3, 5, 7, and 9 days. The expression profile of genes including ABC transporters, SLC transporters, and cytochrome P450 (CYP enzymes was determined using the Affymetrix® Canine GeneChip®. Expression of genes whose probe sets passed a stringent confirmation process was examined. Expression of a few transporter (MDR1, PEPT1 and PEPT2 genes in MDCK cells was confirmed by RT-PCR. The overall gene expression profile was strongly influenced by the type of support the cells were grown on. After 3 days of growth, expression of 28% of the genes was statistically different (1.5-fold cutoff, p < 0.05 between the cells grown on plastic and Transwell® membranes. When cells were differentiated on Transwell® membranes, large changes in gene expression profile were observed during the early stages, which then stabilized after 5–7 days. Only a small number of genes encoding drug absorption related SLC, ABC, and CYP were detected in MDCK cells, and most of them exhibited low hybridization signals. Results from this study provide valuable reference information on endogenous gene expression in MDCK cells that could assist in design of drug-transporter and/or drug-enzyme interaction studies, and help interpret the contributions of various transporters and metabolic enzymes in studies with MDCK cells.

  3. 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.

  4. The fortran programme for the calculation of the absorption and double scattering corrections in cross-section measurements with fast neutrons using the monte Carlo method (1963); Programme fortran pour le calcul des corrections d'absorption et de double diffusion dans les mesures de sections efficaces pour les neutrons rapides par la methode de monte-carlo (1963)

    Energy Technology Data Exchange (ETDEWEB)

    Fernandez, B [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

    1963-07-01

    A calculation for double scattering and absorption corrections in fast neutron scattering experiments using Monte-Carlo method is given. Application to cylindrical target is presented in FORTRAN symbolic language. (author) [French] Un calcul des corrections de double diffusion et d'absorption dans les experiences de diffusion de neutrons rapides par la methode de Monte-Carlo est presente. L'application au cas d'une cible cylindrique est traitee en langage symbolique FORTRAN. (auteur)

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

    Science.gov (United States)

    2009-06-01

    controlled devices provide advantages over passive release devices, as the drug delivery process can be controlled actively after implantation and...mm, 5 μm, 100 Å, Alltech Associates, USA), with methanol and 0.1% trifluoroacetic acid (TFA) in water. The gradient used was 2 % TFA/min, starting

  6. 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

  7. Risk assessment of excess drug and sunscreen absorption via skin with ablative fractional laser resurfacing : optimization of the applied dose for postoperative care.

    Science.gov (United States)

    Chen, Wei-Yu; Fang, Chia-Lang; Al-Suwayeh, Saleh A; Yang, Hung-Hsu; Li, Yi-Ching; Fang, Jia-You

    2013-09-01

    The ablative fractional laser is a new modality used for surgical resurfacing. It is expected that laser treatment can generally deliver drugs into and across the skin, which is toxicologically relevant. The aim of this study was to establish skin absorption characteristics of antibiotics, sunscreens, and macromolecules via laser-treated skin and during postoperative periods. Nude mice were employed as the animal model. The skin received a single irradiation of a fractional CO2 laser, using fluences of 4-10 mJ with spot densities of 100-400 spots/cm(2). In vitro skin permeation using Franz cells was performed. Levels of skin water loss and erythema were evaluated, and histological examinations with staining by hematoxylin and eosin, cyclooxygenase-2, and claudin-1 were carried out. Significant signs of erythema, edema, and scaling of the skin treated with the fractional laser were evident. Inflammatory infiltration and a reduction in tight junctions were also observed. Laser treatment at 6 mJ increased tetracycline and tretinoin fluxes by 70- and 9-fold, respectively. A higher fluence resulted in a greater tetracycline flux, but lower skin deposition. On the other hand, tretinoin skin deposition increased following an increase in the laser fluence. The fractional laser exhibited a negligible effect on modulating oxybenzone absorption. Dextrans with molecular weights of 4 and 10 kDa showed increased fluxes from 0.05 to 11.05 and 38.54 μg/cm(2)/h, respectively. The optimized drug dose for skin treated with the fractional laser was 1/70-1/60 of the regular dose. The skin histology and drug absorption had recovered to a normal status within 2-3 days. Our findings provide the first report on risk assessment of excessive skin absorption after fractional laser resurfacing.

  8. 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.

  9. An off Axis Cavity Enhanced Absorption Spectrometer and a Rapid Scan Spectrometer with a Room-Temperature External Cavity Quantum Cascade Laser

    Science.gov (United States)

    Liu, Xunchen; Kang, Cheolhwa; Xu, Yunjie

    2009-06-01

    Quantum cascade laser (QCL) is a new type of mid-infrared tunable diode lasers with superior output power and mode quality. Recent developments, such as room temperature operation, wide frequency tunability, and narrow line width, make QCLs an ideal light source for high resolution spectroscopy. Two slit jet infrared spectrometers, namely an off-axis cavity enhanced absorption (CEA) spectrometer and a rapid scan spectrometer with an astigmatic multi-pass cell assembly, have been coupled with a newly purchased room temperature tunable mod-hop-free QCL with a frequency coverage from 1592 cm^{-1} to 1698 cm^{-1} and a scan rate of 0.1 cm^{-1}/ms. Our aim is to utilize these two sensitive spectrometers, that are equipped with a molecular jet expansion, to investigate the chiral molecules-(water)_n clusters. To demonstrate the resolution and sensitivity achieved, the rovibrational transitions of the static N_2O gas and the bending rovibrational transitions of the Ar-water complex, a test system, at 1634 cm^{-1} have been measured. D. Hofstetter and J. Faist in High performance quantum cascade lasers and their applications, Vol.89 Springer-Verlag Berlin & Heidelberg, 2003, pp. 61-98. Y. Xu, X. Liu, Z. Su, R. M. Kulkarni, W. S. Tam, C. Kang, I. Leonov and L. D'Agostino, Proc. Spie, 2009, 722208 (1-11). M. J. Weida and D. J. Nesbitt, J. Chem. Phys. 1997, 106, 3078-3089.

  10. Rapid screening for drugs of abuse in biological fluids by ultra high performance liquid chromatography/Orbitrap mass spectrometry.

    Science.gov (United States)

    Jagerdeo, Eshwar; Schaff, Jason E

    2016-08-01

    We present a UPLC(®)-High Resolution Mass Spectrometric method to simultaneously screen for nineteen benzodiazepines, twelve opiates, cocaine and three metabolites, and three "Z-drug" hypnotic sedatives in both blood and urine specimens. Sample processing consists of a high-speed, high-temperature enzymatic hydrolysis for urine samples followed by a rapid supported liquid extraction (SLE). The combination of ultra-high resolution chromatography with high resolution mass spectrometry allows all 38 analytes to be uniquely detected with a ten minute analytical run. Limits of detection for all target analytes are 3ng/mL or better, with only 0.3mL of specimen used for analysis. The combination of low sample volume with fast processing and analysis makes this method a suitable replacement for immunoassay screening of the targeted drug classes, while providing far superior specificity and better limits of detection than can routinely be obtained by immunoassay. Published by Elsevier B.V.

  11. Evaluation of three rapid oral fluid test devices on the screening of multiple drugs of abuse including ketamine.

    Science.gov (United States)

    Tang, Magdalene H Y; Ching, C K; Poon, Simon; Chan, Suzanne S S; Ng, W Y; Lam, M; Wong, C K; Pao, Ronnie; Lau, Angus; Mak, Tony W L

    2018-05-01

    Rapid oral fluid testing (ROFT) devices have been extensively evaluated for their ability to detect common drugs of abuse; however, the performance of such devices on simultaneous screening for ketamine has been scarcely investigated. The present study evaluated three ROFT devices (DrugWipe ® 6S, Ora-Check ® and SalivaScreen ® ) on the detection of ketamine, opiates, methamphetamine, cannabis, cocaine and MDMA. A liquid chromatography tandem mass spectrometry (LCMS) assay was firstly established and validated for confirmation analysis of the six types of drugs and/or their metabolites. In the field test, the three ROFT devices were tested on subjects recruited from substance abuse clinics/rehabilitation centre. Oral fluid was also collected using Quantisal ® for confirmation analysis. A total of 549 samples were collected in the study. LCMS analysis on 491 samples revealed the following drugs: codeine (55%), morphine (49%), heroin (40%), methamphetamine (35%), THC (8%), ketamine (4%) and cocaine (2%). No MDMA-positive cases were observed. Results showed that the overall specificity and accuracy were satisfactory and met the DRUID standard of >80% for all 3 devices. Ora-Check ® had poor sensitivities (ketamine 36%, methamphetamine 63%, opiates 53%, cocaine 60%, THC 0%). DrugWipe ® 6S showed good sensitivities in the methamphetamine (83%) and opiates (93%) tests but performed relatively poorly for ketamine (41%), cocaine (43%) and THC (22%). SalivaScreen ® also demonstrated good sensitivities in the methamphetamine (83%) and opiates (100%) tests, and had the highest sensitivity for ketamine (76%) and cocaine (71%); however, it failed to detect any of the 28 THC-positive cases. The test completion rate (proportion of tests completed with quality control passed) were: 52% (Ora-Check ® ), 78% (SalivaScreen ® ) and 99% (DrugWipe ® 6S). Copyright © 2018 Elsevier B.V. All rights reserved.

  12. 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.

  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. 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.

  15. Rapid preparation process of antiparkinsonian drug Mucuna pruriens silver nanoparticle by bioreduction and their characterization

    Science.gov (United States)

    Arulkumar, Subramanian; Sabesan, Muthukumaran

    2010-01-01

    Backgorund: Development of biologically inspired experimental processes for the synthesis of nanoparticles is evolving an important branch of nanotechnology. Methods: The bioreduction behavior of plant seed extract of Mucuna pruriens in the synthesis of silver nanoparticles was investigated employing UV/visible spectrophotometry, X-ray diffraction (XRD), and transmission electron microscopy (TEM), Fourier transform – infra red (FT- IR). Result: M. pruriens was found to exhibit strong potential for rapid reduction of silver ions. The formation of nanoparticles by this method is extremely rapid, requires no toxic chemicals, and the nanoparticles are stable for several months. Conclusion: The main conclusion is that the bioreduction method to produce nanoparticles is a good alternative to the electrochemical methods and it is expected to be biocompatible. PMID:21808573

  16. A rapid method for the determination of some antihypertensive and antipyretic drugs by thermometric titrimetry.

    Science.gov (United States)

    Abbasi, U M; Chand, F; Bhanger, M I; Memon, S A

    1986-02-01

    A simple and rapid method is described for the direct thermometric determination of milligram amounts of methyl dopa, propranolol hydrochloride, 1-phenyl-3-methylpyrazolone (MPP) and 2,3-dimethyl-1-phenylpyrazol-5-one (phenazone) in the presence of excipients. The compounds are reacted with N'-bromosuccinimide and the heat of reaction is used to determine the end-point of the titration. The time required is approximately 2 min, and the accuracy is analytically acceptable.

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

    Directory of Open Access Journals (Sweden)

    Anand Kumar Maurya

    2013-01-01

    Full Text Available Background: 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. Materials and Methods: 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. 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. Conclusions: 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.

  18. Incorporation of rapid thermodynamic data in fragment-based drug discovery.

    Science.gov (United States)

    Kobe, Akihiro; Caaveiro, Jose M M; Tashiro, Shinya; Kajihara, Daisuke; Kikkawa, Masato; Mitani, Tomoya; Tsumoto, Kouhei

    2013-03-14

    Fragment-based drug discovery (FBDD) has enjoyed increasing popularity in recent years. We introduce SITE (single-injection thermal extinction), a novel thermodynamic methodology that selects high-quality hits early in FBDD. SITE is a fast calorimetric competitive assay suitable for automation that captures the essence of isothermal titration calorimetry but using significantly fewer resources. We describe the principles of SITE and identify a novel family of fragment inhibitors of the enzyme ketosteroid isomerase displaying high values of enthalpic efficiency.

  19. RApid Primary care Initiation of Drug treatment for Transient Ischaemic Attack (RAPID-TIA): study protocol for a pilot randomised controlled trial.

    Science.gov (United States)

    Edwards, Duncan; Fletcher, Kate; Deller, Rachel; McManus, Richard; Lasserson, Daniel; Giles, Matthew; Sims, Don; Norrie, John; McGuire, Graham; Cohn, Simon; Whittle, Fiona; Hobbs, Vikki; Weir, Christopher; Mant, Jonathan

    2013-07-02

    People who have a transient ischaemic attack (TIA) or minor stroke are at high risk of a recurrent stroke, particularly in the first week after the event. Early initiation of secondary prevention drugs is associated with an 80% reduction in risk of stroke recurrence. This raises the question as to whether these drugs should be given before being seen by a specialist--that is, in primary care or in the emergency department. The aims of the RAPID-TIA pilot trial are to determine the feasibility of a randomised controlled trial, to analyse cost effectiveness and to ask: Should general practitioners and emergency doctors (primary care physicians) initiate secondary preventative measures in addition to aspirin in people they see with suspected TIA or minor stroke at the time of referral to a specialist? This is a pilot randomised controlled trial with a sub-study of accuracy of primary care physician diagnosis of TIA. In the pilot trial, we aim to recruit 100 patients from 30 general practices (including out-of-hours general practice centres) and 1 emergency department whom the primary care physician diagnoses with TIA or minor stroke and randomly assign them to usual care (that is, initiation of aspirin and referral to a TIA clinic) or usual care plus additional early initiation of secondary prevention drugs (a blood-pressure lowering protocol, simvastatin 40 mg and dipyridamole 200 mg m/r bd). The primary outcome of the main study will be the number of strokes at 90 days. The diagnostic accuracy sub-study will include these 100 patients and an additional 70 patients in whom the primary care physician thinks the diagnosis of TIA is possible, rather than probable. For the pilot trial, we will report recruitment rate, follow-up rate, a preliminary estimate of the primary event rate and occurrence of any adverse events. For the diagnostic study, we will calculate sensitivity and specificity of primary care physician diagnosis using the final TIA clinic diagnosis as the

  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...... in vivo by the fluorescence imaging technique. In this paper we present a novel approach to compensate for the light absorption in homogeneous turbid media both for the excitation and emission light, utilizing time-resolved fluorescence white Monte Carlo simulations combined with the Beer-Lambert law......-absorption correction and absolute fluorophore concentrations. These results suggest that the technique potentially provides the means to quantify the fluorophore concentration from fluorescence images. © 2011 Society of Photo-Optical Instrumentation Engineers (SPIE)....

  1. Rapid Phospho-Turnover by Receptor Tyrosine Kinases Impacts Downstream Signaling and Drug Binding

    OpenAIRE

    Kleiman, Laura B.; Maiwald, Thomas; Conzelmann, Holger; Lauffenburger, Douglas A.; Sorger, Peter K.

    2011-01-01

    Epidermal growth factor receptors (ErbB1–4) are oncogenic receptor tyrosine kinases (RTKs) that regulate diverse cellular processes. In this study, we combine measurement and mathematical modeling to quantify phospho-turnover at ErbB receptors in human cells and to determine the consequences for signaling and drug binding. We find that phosphotyrosine residues on ErbB1 have half-lives of a few seconds and therefore turn over 100–1000 times in the course of a typical immediate-early response t...

  2. 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.

  3. 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.

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

    Directory of Open Access Journals (Sweden)

    Paresh Dave

    Full Text Available 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

  5. Rapid diagnosis of drug resistance to fluoroquinolones, amikacin, capreomycin, kanamycin and ethambutol using genotype MTBDRsl assay: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Yan Feng

    Full Text Available BACKGROUND: There are urgent needs for rapid and accurate drug susceptibility testing of M. tuberculosis. GenoType MTBDRsl is a new molecular kit designed for rapid identification of the resistance to the second-line antituberculosis drugs with a single strip. In recent years, it has been evaluated in many settings, but with varied results. The aim of this meta-analysis was to synthesize the latest data on the diagnostic accuracy of GenoType MTBDRsl in detecting drug resistance to fluoroquinolones, amikacin, capreomycin, kanamycin and ethambutol, in comparison with the phenotypic drug susceptibility test. METHODS: This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA guideline. The search terms of "MTBDRsl" and "tuberculosis" were used on PubMed, EMBASE, and Web of Science. QUADAS-2 was used to assess the quality of included studies. Data were analyzed by Meta-Disc 1.4. We calculated the sensitivity, specificity, positive likelihood ratio (PLR, negative likelihood ratio (NLR, diagnostic odds ratio (DOR and corresponding 95% confidence interval (CI for each study. From these calculations, forest plots and summary receiver operating characteristic (SROC curves were produced. RESULTS: Patient selection bias as well as flow and timing bias were observed in most studies. The summarized sensitivity (95% CI was 0.874(0.845-0.899, 0.826(0.777-0.869, 0.820(0.772-0.862, 0.444(0.396-0.492, and 0.679(0.652-0.706 for fluoroquinolones, amikacin, capreomycin, kanamycin, and ethambutol, respectively. The specificity (95% CI was 0.971(0.961-0.980, 0.995(0.987-0.998, 0.973(0.963-0.981, 0.993(0.985-0.997, and 0.799(0.773-0.823, respectively. The AUC (standard error were 0.9754(0.0203, 0.9300(0.0598, 0.9885(0.0038, 0.9689(0.0359, and 0.6846(0.0550, respectively. CONCLUSION: Genotype MTBDRsl showed good accuracy for detecting drug resistance to fluoroquinolones, amikacin and capreomycin, but it may not be an

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

    International Nuclear Information System (INIS)

    Nielen, M.W.F.; Hooijerink, H.; Claassen, F.C.; Engelen, M.C. van; Beek, T.A. van

    2009-01-01

    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 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

  7. 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.

  8. 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...... 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...

  9. 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

    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...... 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. CONCLUSIONS: The main challenges in designing this trial were maintaining a balance between a robust intervention...... to support effective behaviour change and introducing practices that would be sustainable in a real-life situation in tropical Africa; as well as achieving a detailed evaluation without inadvertently influencing prescribing behaviour.Trial registration: Trial registration: NCT01194557 registered...

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

    Science.gov (United States)

    Chen, Hui-Ru; Rairat, Tirawat; Loh, Shih-Hurng; Wu, Yu-Chieh; Vickroy, Thomas W.

    2017-01-01

    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. PMID:28797073

  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 ...

  12. Evaluation of rapid MTT tube method for detection of drug susceptibility of mycobacterium tuberculosis to rifampicin and isoniazid

    Directory of Open Access Journals (Sweden)

    Raut U

    2008-01-01

    Full Text Available Purpose: To evaluate MTT method for detection of drug resistance to rifampicin and isoniazid in M.tuberculosis . This method utilises the ability of viable mycobacterial cells to reduce MTT( 3-4,5-dimethylthiazol-2-yl-2, 5-diphenyl tetrazolium bromide. Methods: The method was standardised with known resistant and sensitive strains of M.tuberculosis and was then extended to 50 clinical isolates. An inoculum of 10 7 cfu/mL was prepared in Middlebrook 7H9 medium supplemented with oleic acid, albumin, dextrose and catalase. For each drug three tubes were used, one with INH(0.2μg/mL or RIF(1μg/mL, another as inoculum control and third as blank control. These were incubated at 37°C for four and seven days respectively for RIF and INH after which MTT assay was performed. Results were read visually and by colorimeter at 570 nm. Relative optical density unit (RODU of 0.2 was taken as cut off. Results were compared with drug sensitivity obtained by proportion method using LJ medium. Results: For rifampicin, concordance with proportion method was 90% by visual and 94% by RODU. Sensitivity and specificity was 86.8% and 100% respectively by visual method and 95.2% and 87.5% respectively by RODU. For Isoniazid, concordance was 94% and sensitivity and specificity was 94.7 and 91.7% respectively by both visual and RODU. Conclusions: MTT assay proved to be rapid and cheap method for performing drug sensitivity of M.tuberculosis

  13. A Cluster Randomised Trial Introducing Rapid Diagnostic Tests into Registered Drug Shops in Uganda: Impact on Appropriate Treatment of Malaria

    Science.gov (United States)

    Mbonye, Anthony K.; Magnussen, Pascal; Lal, Sham; Hansen, Kristian S.; Cundill, Bonnie; Chandler, Clare; Clarke, Siân E.

    2015-01-01

    Background Inappropriate treatment of malaria is widely reported particularly in areas where there is poor access to health facilities and self-treatment of fevers with anti-malarial drugs bought in shops is the most common form of care-seeking. The main objective of the study was to examine 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 of introducing mRDTs in registered drug shops was implemented in 20 geographical clusters of drug shops in Mukono district, central Uganda. Ten clusters were randomly allocated to the intervention (diagnostic confirmation of malaria by mRDT followed by ACT) and ten clusters to the control arm (presumptive treatment of fevers with ACT). Treatment decisions by providers were validated by microscopy on a reference blood slide collected at the time of consultation. The primary outcome was the proportion of febrile patients receiving appropriate treatment with ACT defined as: malaria patients with microscopically-confirmed presence of parasites in a peripheral blood smear receiving ACT or rectal artesunate, and patients with no malaria parasites not given ACT. Findings A total of 15,517 eligible patients (8672 intervention and 6845 control) received treatment for fever between January-December 2011. The proportion of febrile patients who received appropriate ACT treatment was 72·9% versus 33·7% in the control arm; a difference of 36·1% (95% CI: 21·3 – 50·9), pshop vendors adhered to the mRDT results, reducing over-treatment of malaria by 72·6% (95% CI: 46·7– 98·4), pshop vendors using presumptive diagnosis (control arm). Conclusion Diagnostic testing with mRDTs compared to presumptive treatment of fevers implemented in registered drug shops substantially improved appropriate

  14. 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

  15. 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

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

    Science.gov (United States)

    Jennum, Poul; Christensen, Julie AE; Zoetmulder, Marielle

    2016-01-01

    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. PMID:27186147

  17. Rapid identification of drug resistant Candida species causing recurrent vulvovaginal candidiasis.

    Science.gov (United States)

    Diba, Kambiz; Namaki, Atefeh; Ayatolahi, Haleh; Hanifian, Haleh

    2012-01-01

    Some yeast agents including Candida albicans, Candida tropicalis and Candida glabrata have a role in recurrent vulvovaginal candidiasis. We studied the frequency of both common and recurrent vulvovaginal candidiasis in symptomatic cases which were referred to Urmia Medical Sciences University related gynecology clinics using morphologic and molecular methods. The aim of this study was the identification of Candida species isolated from recurrent vulvovaginal candidiasis cases using a rapid and reliable molecular method. Vaginal swabs obtained from each case, were cultured on differential media including cornmeal agar and CHROM agar Candida. After 48 hours at 37℃, the cultures were studied for growth characteristics and color production respectively. All isolates were identified using the molecular method of PCR - restriction fragment length polymorphism. Among all clinical specimens, we detected 19 ( 16 % ) non fungal agents, 87 ( 82.1 % ) yeasts and 2 ( 1.9 % ) multiple infections. The yeast isolates identified morphologically included Candida albicans ( n = 62 ), Candida glabrata ( n = 9 ), Candida tropicalis ( n = 8 ), Candida parapsilosis ( n = 8 ) and Candida guilliermondii and Candida krusei ( n = 1 each ). We also obtained very similar results for Candida albicans, Candida glabrata and Candida tropicalis as the most common clinical isolates, by using PCR - Restriction Fragment Length Polymorphism. Use of two differential methods, morphologic and molecular, enabled us to identify most medically important Candida species which particularly cause recurrent vulvovaginal candidiasis.

  18. 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.

  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 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....

  20. Influences of doping mesoporous magnesium silicate on water absorption, drug release, degradability, apatite-mineralization and primary cells responses to calcium sulfate based bone cements

    International Nuclear Information System (INIS)

    Gu, Zhengrong; Wang, Sicheng; Weng, Weizong; Chen, Xiao; Cao, Liehu; Wei, Jie; Shin, Jung-Woog; Su, Jiacan

    2017-01-01

    In this study, composite cements containing mesoporous magnesium silicate (m-MS) and calcium sulfate (CS) were fabricated. The results revealed that the setting time of the m-MS/CS composite cements (m-MSC) slightly prolonged with the increase of m-MS content while the compressive strength suffered a little loss. The doping of m-MS improved the water absorption, drug release (vancomycin) and degradability of the m-MSC in Tris-HCl solution (pH = 7.4). In addition, addition of m-MS facilitated the apatite-mineralization of m-MSC in simulated body fluid (SBF), indicating good bioactivity. For cell cultural experiments, the results revealed that the m-MSC promoted the cells adhesion and proliferation, and improved the alkaline phosphatase (ALP) activity of MC3T3-E1 cells, revealing good cytocompatibility. It could be suggested that the m-MSC might be promising cements biomaterials for bone tissue regeneration. - Highlights: • The mesoporous magnesium silicate and calcium sulfate composite was fabricated. • The composite possessed good water absorption and drug release of vancomycin. • The bioactive composite could enhance the in vivo apatite formation in SBF. • The composite promoted cell adhesion, proliferation and osteogenic differentiation.

  1. Influences of doping mesoporous magnesium silicate on water absorption, drug release, degradability, apatite-mineralization and primary cells responses to calcium sulfate based bone cements

    Energy Technology Data Exchange (ETDEWEB)

    Gu, Zhengrong [Department of Trauma Orthopaedics, Changhai Hospital, Second Military Medical University, Shanghai 200433 (China); The Department of Orthopaedics, Jing' an District Centre Hospital of Shanghai (Huashan Hospital Fudan University Jing' An Branch), 200040 (China); Wang, Sicheng [Department of Trauma Orthopaedics, Changhai Hospital, Second Military Medical University, Shanghai 200433 (China); Department of Orthopaedics, Zhongye Hospital, Shanghai 200941 (China); Weng, Weizong; Chen, Xiao; Cao, Liehu [Department of Trauma Orthopaedics, Changhai Hospital, Second Military Medical University, Shanghai 200433 (China); Wei, Jie [Key Laboratory for Ultrafine Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237 (China); Shin, Jung-Woog [Department of Biomedical Engineering, Inje University, Gimhae, 621749 (Korea, Republic of); Su, Jiacan, E-mail: jiacansu@sina.com [Department of Trauma Orthopaedics, Changhai Hospital, Second Military Medical University, Shanghai 200433 (China)

    2017-06-01

    In this study, composite cements containing mesoporous magnesium silicate (m-MS) and calcium sulfate (CS) were fabricated. The results revealed that the setting time of the m-MS/CS composite cements (m-MSC) slightly prolonged with the increase of m-MS content while the compressive strength suffered a little loss. The doping of m-MS improved the water absorption, drug release (vancomycin) and degradability of the m-MSC in Tris-HCl solution (pH = 7.4). In addition, addition of m-MS facilitated the apatite-mineralization of m-MSC in simulated body fluid (SBF), indicating good bioactivity. For cell cultural experiments, the results revealed that the m-MSC promoted the cells adhesion and proliferation, and improved the alkaline phosphatase (ALP) activity of MC3T3-E1 cells, revealing good cytocompatibility. It could be suggested that the m-MSC might be promising cements biomaterials for bone tissue regeneration. - Highlights: • The mesoporous magnesium silicate and calcium sulfate composite was fabricated. • The composite possessed good water absorption and drug release of vancomycin. • The bioactive composite could enhance the in vivo apatite formation in SBF. • The composite promoted cell adhesion, proliferation and osteogenic differentiation.

  2. Rapid colorimetric detection of p53 protein function using DNA-gold nanoconjugates with applications for drug discovery and cancer diagnostics.

    Science.gov (United States)

    Assah, Enock; Goh, Walter; Zheng, Xin Ting; Lim, Ting Xiang; Li, Jun; Lane, David; Ghadessy, Farid; Tan, Yen Nee

    2018-05-05

    The tumor suppressor protein p53 plays a central role in preventing cancer through interaction with DNA response elements (REs) to regulate target gene expression in cells. Due to its significance in cancer biology, relentless efforts have been directed toward understanding p53-DNA interactions for the development of cancer therapeutics and diagnostics. In this paper, we report a rapid, label-free and versatile colorimetric assay to detect wildtype p53 DNA-binding function in complex solutions. The assay design is based on a concept that alters interparticle-distances between RE-AuNPs from a crosslinking effect induced through tetramerization of wildtype p53 protein (p53-WT) upon binding to canonical DNA motifs modified on gold nanoparticles (RE-AuNPs). This leads to a visible solution color change from red to blue, which is quantifiable by the UV- visible absorption spectra with a detection limit of 5 nM. Contrastingly, no color change was observed for the binding-deficient p53 mutants and non-specific proteins due to their inability to crosslink RE-AuNPs. Based on this sensing principle, we further demonstrate its utility for fast detection of drug-induced DNA binding function to cancer-associated Y220C mutant p53 protein using well-established reactivating compounds. By exploiting the dominant-negative property of mutant p53 over p53-WT and interactions with RE-AuNPs, this assay is configurable to detect low numbers of mutant p53 expressing cells in miniscule sample fractions obtained from typical core needle biopsy-sized tissues without signal attrition, alluding to the potential for biopsy sampling in cancer diagnostics or for defining cancer margins. This nanogold enabled colorimetric assay provides a facile yet robust method for studying important parameters influencing p53-DNA interactions with great promises for clinically pertinent applications. Copyright © 2018 Elsevier B.V. All rights reserved.

  3. Potentiation of intraocular absorption and drug metabolism of N-acetylcarnosine lubricant eye drops: drug interaction with sight threatening lipid peroxides in the treatment for age-related eye diseases.

    Science.gov (United States)

    Babizhayev, Mark A

    2009-01-01

    lenses obtained from patients with senile and complicated cataracts as compared to normal donors. Utilizing the pharmacokinetic studies and the specific purity N-acetylcarnosine (NAC) ingredient as a source of pharmacological principal L-carnosine, we have created an ophthalmic time-release prodrug form combined with a muco-adhesive lubricant compound carboxymethylcellulose and other essential corneal absorption promoter excipients tailoring the increased intraocular absorption of L-carnosine in the aqueous humor and optimizing its specific effect in producing the basic antioxidant activity in vivo and reducing toxic effects of lipid peroxides to the crystalline lens. L-Carnosine that finds its way into the aqueous humor can accumulate in the lens tissue for a reasonable period of time. However, administration of pure L-carnosine (1% solution) to the rabbit eye (instillation, subconjunctival injection) does not lead to accumulation of this natural compound in the aqueous humor over 30 min in concentration exceeding that in the placebo-treated matched eyes, and its effective concentration is exhausted more rapidly. The NAC prodrug eye drops optimize the clinical effects for the treatment of ophthalmic disorders (such as prevention and reversal of cataracts in human and animal [canine] eyes). The data provided predict a particular NAC ophthalmic prodrug's clinical effect; the suitable magnitude and duration of this effect suggest dose-related bioavailability of L-camosine released from NAC in the aqueous humor of the anterior eye segment. The ophthalmic NAC drug shows promise in the treatment of a range of ophthalmic disorders which have a component of oxidative stress in their genesis (including cataract and after-cataract, glaucoma, dry eye, vitreous floaters, inflammatory disorders, corneal, retinal and systemic diseases [such as diabetes mellitus and its ophthalmic complications]). The clinical efficacy of N-acetylcarnosine lubricant eye drops in ripe cataracts and

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

    International Nuclear Information System (INIS)

    Szultka, Malgorzata; Kegler, Ricarda; Fuchs, Patricia; Olszowy, Pawel; Miekisch, Wolfram; Schubert, Jochen K.; Buszewski, Boguslaw; Mundkowski, Ralf G.

    2010-01-01

    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.

  5. 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.

  6. [Oral loading dose of phenytoin in the treatment of serial seizures, prevention of seizure recurrence and rapid drug substitution].

    Science.gov (United States)

    Sokić, D; Janković, S M

    1994-01-01

    Over a period of nine months twenty-five epileptic patients were treated with the oral loading dose of phenytoin. The dose ranged from 12 to 23 mg/kg body weight during 1 to 12 hours. In 20 patients with serial seizures or intolerance to other antiepileptic drugs this treatment was effective. Seizures also stopped in 2 of 4 patients with serial partial motor seizures. These 2 patients required both higher loading dose and faster rate of administration than the other patients. A patient with epilepsia partialis continua failed to respond to the treatment. Patients that received phenytoin through the naso-gastric tube, in respect to oral administration, required higher doses to obtain therapeutic plasma levels of phenytoin. One patient had mild nausea, 3 mild dizziness, and 1 tinitus on the first day of the treatment. There was no correlation between a given dose and the achieved phenytoin plasma levels. In our opinion the therapy with oral loading dose of phenytoin is highly effective in the treatment of serial generalized seizures and rapid antiepileptic drug substitution, and partially effective in the prevention of partial motor seizures. It produces only mild and transient side-effects.

  7. 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)

  8. Rapid diagnosis of multidrug resistance in cancer by electrochemical sensor based on carbon nanotubes-drug supramolecular nanocomposites.

    Science.gov (United States)

    Zhang, Haijun; Jiang, Hui; Sun, Feifei; Wang, Huangping; Zhao, Juan; Chen, Baoan; Wang, Xuemei

    2011-03-15

    The multidrug resistance (MDR) in cancer is a major chemotherapy obstacle, rendering many currently available chemotherapeutic drugs ineffective. The aim of this study was to explore the new strategy to early diagnose the MDR by electrochemical sensor based on carbon nanotubes-drug supramolecular interaction. The carbon nanotubes modified glassy carbon electrodes (CNTs/GCE) were directly immersed into the cells suspension of the sensitive leukemia cells K562 and/or its MDR cells K562/A02 to detect the response of the electrochemical probe of daunorubicin (DNR) residues after incubated with cells for 1h. The fresh evidence from the electrochemical studies based on CNTs/GCE demonstrated that the homogeneous, label-free strategy could directly measure the function of cell membrane transporters in MDR cancer cells, identify the cell phenotype (sensitive or MDR). When the different ratios of the sensitive leukemia cells K562 and its MDR ones K562/A02 were applied as a model of MDR levels to simulate the MDR occurrence in cancer, the cathodic peak current showed good linear response to the fraction of MDR with a correlation coefficient of 0.995. Therefore, the MDR fraction can be easily predicted based on the calibration curve of the cathodic peak current versus the fraction of MDR. These results indicated that the sensing strategy could provide a powerful tool for assessment of MDR in cancer. The new electrochemical sensor based on carbon nanotubes-drug supramolecular nanocomposites could represent promising approach in the rapid diagnosis of MDR in cancer. Copyright © 2011 Elsevier B.V. All rights reserved.

  9. 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

  10. 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.

  11. Rapid molecular detection of rifampicin resistance facilitates early diagnosis and treatment of multi-drug resistant tuberculosis: case control study.

    Directory of Open Access Journals (Sweden)

    Philly O'Riordan

    2008-09-01

    Full Text Available Multi-drug resistant tuberculosis (MDR-TB is a major public health concern since diagnosis is often delayed, increasing the risk of spread to the community and health care workers. Treatment is prolonged, and the total cost of treating a single case is high. Diagnosis has traditionally relied upon clinical suspicion, based on risk factors and culture with sensitivity testing, a process that can take weeks or months. Rapid diagnostic molecular techniques have the potential to shorten the time to commencing appropriate therapy, but have not been put to the test under field conditions.This retrospective case-control study aimed to identify risk factors for MDR-TB, and analyse the impact of testing for rifampicin resistance using RNA polymerase B (rpoB mutations as a surrogate for MDR-TB. Forty two MDR-TB cases and 84 fully sensitive TB controls were matched by date of diagnosis; and factors including demographics, clinical presentation, microbiology findings, management and outcome were analysed using their medical records. Conventionally recognised risk factors for MDR-TB were absent in almost half (43% of the cases, and 15% of cases were asymptomatic. A significant number of MDR-TB cases were identified in new entrants to the country. Using rpoB mutation testing, the time to diagnosis of MDR-TB was dramatically shortened by a median of 6 weeks, allowing patients to be commenced on appropriate therapy a median of 51days earlier than those diagnosed by conventional culture and sensitivity testing.MDR-TB is frequently an unexpected finding, may be asymptomatic, and is particularly prevalent among TB infected new entrants to the country. Molecular resistance testing of all acid fast bacilli positive specimens has the potential to rapidly identify MDR-TB patients and commence them on appropriate therapy significantly earlier than by conventional methods.

  12. 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...

  13. Development of a Method for Rapid Determination of Morpholine in Juices and Drugs by Gas Chromatography-Mass Spectrometry

    Directory of Open Access Journals (Sweden)

    Mengsi Cao

    2018-01-01

    Full Text Available A reliable derivatization method has been developed to detect and quantify morpholine in apple juices and ibuprofen with gas chromatography-mass spectrometry. Morpholine can react with sodium nitrite under acidic condition to produce stable and volatile N-nitrosomorpholine derivative. In this experiment, various factors affecting the derivatization and extraction process were optimized, including volume and concentration of hydrochloric acid, quantity of sodium nitrite, derivatization temperature, derivatization time, extraction reagents, and extraction time. The derivative was extracted with dichloromethane and determined by gas chromatography-mass spectrometry. The linearity range of morpholine was 10–500 μg·L−1 with good correlation, and limits of detection (LOD and limits of quantification (LOQ were 7.3 μg·L−1 and 24.4 μg·L−1, respectively. Low, medium, and high concentrations of morpholine were added in apple juices and ibuprofen samples to evaluate standard recovery rate and relative standard deviation. The spiked recovery rate ranged from 94.3% to 109.0%, and the intraday repeatability and interday reproducibility were 2.0%–4.4% and 3.3%–7.0%, respectively. The developed method has good accuracy and precision. This quantitative method for morpholine is simple, sensitive, rapid, and low cost and can successfully be applied to analyze the residual morpholine in apple juices and drug samples.

  14. DESI-MS2: a rapid and innovative method for trace analysis of six cytostatic drugs in health care setting.

    Science.gov (United States)

    Fabrizi, Giovanni; Fioretti, Marzia; Rocca, Lucia Mainero; Curini, Roberta

    2012-05-01

    With the aim of establishing exposure levels for hospital personnel preparing and administering cytostatic drugs (CDs), here, we present an innovative screening method based on the use of the desorption electrospray ionization (DESI) interface coupled with a hybrid quadrupole linear ion trap mass spectrometer. A rapid, simple, and sensitive procedure was developed for the simultaneous surface monitoring of cyclophosphamide, dacarbazine, methotrexate, vincristine, gemcitabine, and cytarabine. Since analytes were in the solid state, a novel approach based on the use of passive samplers was combined with the direct analysis of wipes. A PTFE-printed glass slide was used as a passive sampler, while hydrophobic centers of Swiffer® cloths were judged extremely efficient as wipe samplers. After the sampling period, the CD collectors were directly processed with the DESI-MS system without any further treatment. MS/MS confirmatory analysis was conducted using selected reaction monitoring in the positive ion mode and detection limits were evaluated. Values were at the picograms per square millimeter levels on the passive collector and at the picograms per square centimeter levels for the wipe ones. Direct determination on solid-state samples combined with mass spectrometry selectivity provided a powerful tool so far unapplied to occupational hygiene.

  15. 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

    questionnaire to capture data on drug shops (n=65) including provider characteristics, knowledge on treatment of malaria, previous training received, type of drugs stocked, reported drug sales, and record keeping practices; and a patient questionnaire to capture data from febrile patients (n=540) exiting drug...

  16. Statins, fibrates, nicotinic acid, cholesterol absorption inhibitors, anion-exchange resins, omega-3 fatty acids: which drugs for which patients?

    Science.gov (United States)

    Drexel, Heinz

    2009-12-01

    Classes of lipid lowering drugs differ strongly with respect to the types of lipids or lipoproteins they predominantly affect. Statins inhibit the de-novo synthesis of cholesterol. Consequently, the liver produces less VLDL, and the serum concentration primarily of LDL cholesterol (but, to a lesser extent, also of triglycerides) is lowered. Further, statins somewhat increase HDL cholesterol. There is abundant evidence that statins lower the rate of cardiovascular events. Cardiovascular risk reduction is the better, the lower the LDL cholesterol values achieved with statin therapy are. Some evidence is available that anion exchange resins which also decrease LDL cholesterol decrease vascular risk, too. This is not the case for the ezetimibe, which strongly lowers LDL cholesterol: its potential to decrease vascular risk remains to be proven. In contrast evidence for cardiovascular risk reduction through the mainly triglyceride lowering fibrates as well as for niacin is available. Niacin is the most potent HDL increasing drug currently available and besides increasing HDL cholesterol efficaciously lowers triglycerides and LDL cholesterol. Large ongoing trials address the decisive question whether treatment with fibrates and niacin provides additional cardiovascular risk reduction when given in addition to statin treatment.

  17. Laser-based absorption spectroscopy as a technique for rapid in-line analysis of respired gas concentrations of O2 and CO2.

    Science.gov (United States)

    Cummings, Beth; Hamilton, Michelle L; Ciaffoni, Luca; Pragnell, Timothy R; Peverall, Rob; Ritchie, Grant A D; Hancock, Gus; Robbins, Peter A

    2011-07-01

    The use of sidestream analyzers for respired gas analysis is almost universal. However, they are not ideal for measurements of respiratory gas exchange because the analyses are both temporally dissociated from measurements of respiratory flow and also not generally conducted under the same physical conditions. This study explores the possibility of constructing an all optical, fast response, in-line breath analyzer for oxygen and carbon dioxide. Using direct absorption spectroscopy with a diode laser operating at a wavelength near 2 μm, measurements of expired carbon dioxide concentrations were obtained with an absolute limit of detection of 0.04% at a time resolution of 10 ms. Simultaneously, cavity enhanced absorption spectroscopy at a wavelength near 760 nm was employed to obtain measurements of expired oxygen concentrations with an absolute limit of detection of 0.26% at a time resolution of 10 ms. We conclude that laser-based absorption spectroscopy is a promising technology for in-line analysis of respired carbon dioxide and oxygen concentrations.

  18. 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

    2011-01-01

    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 584873 suspect fever cases). An estimated 516576 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 achieved in ACT

  19. Phosphodiesterase (PDE5) inhibition assay for rapid detection of erectile dysfunction drugs and analogs in sexual enhancement products.

    Science.gov (United States)

    Santillo, Michael F; Mapa, Mapa S T

    2018-02-28

    Products marketed as dietary supplements for sexual enhancement are frequently adulterated with phosphodiesterase-5 (PDE5) inhibitors, which are erectile dysfunction drugs or their analogs that can cause adverse health effects. Due to widespread adulteration, a rapid screening assay was developed to detect PDE5 inhibitors in adulterated products. The assay employs fluorescence detection and is based on measuring inhibition of PDE5 activity, the pharmacological mechanism shared among the adulterants. Initially, the assay reaction scheme was established and characterized, followed by analysis of 9 representative PDE5 inhibitors (IC 50 , 0.4-4.0 ng mL -1 ), demonstrating sensitive detection in matrix-free solutions. Next, dietary supplements serving as matrix blanks (n = 25) were analyzed to determine matrix interference and establish a threshold value; there were no false positives. Finally, matrix blanks were spiked with 9 individual PDE5 inhibitors, along with several mixtures. All 9 adulterants were successfully detected (≤ 5 % false negative rate; n = 20) at a concentration of 1.00 mg g -1 , which is over 5 times lower than concentrations commonly encountered in adulterated products. A major distinction of the PDE5 inhibition assay is the ability to detect adulterants without prior knowledge of their chemical structures, demonstrating a broad-based detection capability that can address a continuously evolving threat of new adulterants. The PDE5 inhibition assay can analyze over 40 samples simultaneously within 15 minutes and involves a single incubation step and simple data analysis, all of which are advantageous for combating the widespread adulteration of sex-enhancement products. Published 2018. This article is a U.S. Government work and is in the public domain in the USA.

  20. Numerate Intends to Join ATOM Consortium to Rapidly Accelerate Preclinical Drug Development | Frederick National Laboratory for Cancer Research

    Science.gov (United States)

    SAN FRANCISCO – Computational drug design company Numerate has signed a letter of intent to join an open consortium of scientists staffed from two U.S. national laboratories, industry, and academia working to transform drug discovery and developmen

  1. Rapid determination of main components by means of flame-atomic-absorption spectrometry for chromium, silicon and tungsten in CrSiW materials

    International Nuclear Information System (INIS)

    Mueller, E.; Stahlberg, R.

    1985-01-01

    The application of Flame-Atomic-Absorption Spectrometry (FAAS) for determining chromium, silicon and tungsten in CrSiW materials is described. The FAAS determinations of the main components are shown under optimum conditions. Sufficient precision and reliability have been achieved for routine analysis. The application of a mixture of acids for preparing CrSiW solutions is proposed. The preparation of samples is discussed in detail. Optimum conditions are recommended for determining chromium, silicon and tungsten using one solution only. (orig.) [de

  2. 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

    Background In most pharmacokinetic studies, the oral absorption of drugs is impaired during migraine attacks but exceptions occur. A study on gastric emptying using gastric scintigraphy indicated that gastric stasis also occurs interictally in migraine. These studies were reviewed critically. Res...

  3. Nasal Delivery of High Molecular Weight Drugs

    Directory of Open Access Journals (Sweden)

    Erdal Cevher

    2009-09-01

    Full Text Available Nasal drug delivery may be used for either local or systemic effects. Low molecular weight drugs with are rapidly absorbed through nasal mucosa. The main reasons for this are the high permeability, fairly wide absorption area, porous and thin endothelial basement membrane of the nasal epithelium. Despite the many advantages of the nasal route, limitations such as the high molecular weight (HMW of drugs may impede drug absorption through the nasal mucosa. Recent studies have focused particularly on the nasal application of HMW therapeutic agents such as peptide-protein drugs and vaccines intended for systemic effects. Due to their hydrophilic structure, the nasal bioavailability of peptide and protein drugs is normally less than 1%. Besides their weak mucosal membrane permeability and enzymatic degradation in nasal mucosa, these drugs are rapidly cleared from the nasal cavity after administration because of mucociliary clearance. There are many approaches for increasing the residence time of drug formulations in the nasal cavity resulting in enhanced drug absorption. In this review article, nasal route and transport mechanisms across the nasal mucosa will be briefly presented. In the second part, current studies regarding the nasal application of macromolecular drugs and vaccines with nanoand micro-particulate carrier systems will be summarised.

  4. Study of small-cell lung cancer cell-based sensor and its applications in chemotherapy effects rapid evaluation for anticancer drugs.

    Science.gov (United States)

    Guohua, Hui; Hongyang, Lu; Zhiming, Jiang; Danhua, Zhu; Haifang, Wan

    2017-11-15

    Small cell lung cancer (SCLC) is a smoking-related cancer disease. Despite improvement in clinical survival, SCLC outcome remains extremely poor. Cisplatin (DDP) is the first-line chemotherapy drug for SCLC, but the choice of second-line chemotherapy drugs is not clear. In this paper, a SCLC cell-based sensor was proposed, and its applications in chemotherapy effects rapid evaluation for anticancer drugs were investigated. SCLC cell lines lung adenocarcinoma cell (LTEP-P) and DDP-resistant lung adenocarcinoma cell (LTEP-P/DDP-1.0) are cultured on carbon screen-printed electrode (CSPE) to fabricate integrated cell-based sensor. Several chemotherapy anticancer drugs, including cisplatin, ifosmamide, gemcitabine, paclitaxel, docetaxel, vinorelbine, etoposide, camptothecin, and topotecan, are selected as experimental chemicals. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) tests are conducted to evaluate chemotherapy drug effects on LTEP-P and LTEP-P/DDP-1.0 cell lines. Electrical cell-substrate impedance sensing (ECIS) responses to anti-tumor chemicals are measured and processed by double-layered cascaded stochastic resonance (DCSR). Cisplatin solutions in different concentrations measurement results demonstrate that LTEP-P cell-based sensor presents quantitative analysis abilities for cisplatin and topotecan. Cisplatin and its mixtures can also be discriminated. Results demonstrate that LTEP-P cell-based sensor sensitively evaluates chemotherapy drugs' apoptosis function to SCLC cells. LTEP-P/DDP-1.0 cell-based sensor responses demonstrate that gemcitabine, vinorelbine, and camptothecin are ideal second-line drugs for clinical post-cisplatin therapy than other drugs according to MTT test results. This work provides a novel way for SCLC second-line clinical chemotherapy drug screening. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. 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.

  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. Rapid analysis of NSAIDs binding to β-cyclodextrin using the simultaneous measurement of absorption and circular dichroism with a novel multi-cell low-volume device.

    Science.gov (United States)

    Aboel Dahab, Ali; El-Hag, Dhia

    2012-10-01

    One of the relatively recent and most widely used approaches to reduce side effects associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs) is the complexation of NSAIDs with Cyclodextrins (CyD). So far, CyD interaction with drugs is not well understood. There have been many reports along these lines; however, rarely do these studies exploit the full potential of optical techniques. The purpose of this work is to produce a versatile, compact, low-volume, routine apparatus for the simultaneous measurements of absorbance and circular dichroism (CD) which allows for the concurrent use of three different pathlengths for binding studies of NSAIDs/CyD as a function of pH. A new rotating multi-cell holder which holds four cells was designed and manufactured. The work was achieved using an effective novel method for binding titration employing four separate flow cells connected in series in a flow system involving a titration flask and a pump. The pK(a), binding constants, stoichiometry and structural co-conformations of NSAIDs/β-CyD complexes were elucidated and determined with accuracy. The system proved to be efficient and the analysis time was reduced to less than or equal to one fourth of total analysis time used in one-cell systems, with possible automation for high-throughput analysis.

  8. Isavuconazole absorption following oral administration in healthy subjects is comparable to intravenous dosing, and is not affected by food, or drugs that alter stomach pH.

    Science.gov (United States)

    Schmitt-Hoffmann, Anne; Desai, Amit; Kowalski, Donna; Pearlman, Helene; Yamazaki, Takao; Townsend, Robert

    2016-08-01

    Two openlabel, single-dose, randomized crossover studies and one open-label, multiple-dose, parallel group study in healthy volunteers were conducted with the prodrug, isavuconazonium sulfate, to determine absolute bioavailability of the active triazole, isavuconazole (EudraCT 2007-004949-15; n = 14), and the effect of food (EudraCT 2007- 004940-63; n = 26), and pH (NCT02128893; n = 24) on the absorption of isavuconazole. Isavuconazonium sulfate 744 mg designed to deliver 400 mg of the active triazole isavuconazole was administered in the absolute bioavailability (oral or intravenous (IV) (2-hour infusion)) and food-effect studies (oral). In the pH-effect study, isavuconazonium sulfate 372 mg designed to deliver 200 mg of isavuconazole was administered orally three times daily (t.i.d.) for 2 days, followed by a single daily oral dose for 3 days, in the presence of steady state esomeprazole dosed orally at 40 mg/day. Isavuconazole was well tolerated in each study. Bioavailability: Geometric least squares mean ratios (GLSMR; oral/IV) for isavuconazole AUC∞, and Cmax were 98% (90% confidence interval (CI): 94, 101) and 78% (90% CI: 72, 85), respectively. Food-effect: GLSMR (fed/fasted) for AUC∞ and Cmax of isavuconazole in plasma were 110% (90% CI: 102, 118) and 92% (90% CI: 86, 98), respectively. Median tmax was 5 hours with food and 3 hours under fasted conditions. pH-effect: GLSMR for isavuconazole AUCtau and Cmax were 108% (90% CI: 89, 130) and 105% (90% CI: 89, 124), respectively. Orally administered isavuconazonium sulfate effectively delivers isavuconazole, as evidenced by the fact that oral isavuconazole is bioequivalent to the IV formulation. Dose adjustments are not required when switching between oral and IV formulations, regardless of food or drugs that increase gastric pH.

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

    Science.gov (United States)

    Christiansen, Martin Lau; Holm, Rene; Abrahamsson, Bertil; Jacobsen, Jette; Kristensen, Jakob; Andersen, Jens Rikardt; Müllertz, Anette

    2016-03-10

    Positive food effects may be observed for low aqueous soluble compounds, these effects could potentially be circumvented using lipid based formulations. However, as all compounds are not chemically stable in lipid based systems, alternative dosage regimes could be investigated to evade 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 (SNEDDS) with a conventional cinnarizine tablet could reduce the observed food-effect. A commercial conventional cinnarizine tablet was dosed to 10 healthy volunteers in a cross-over design in both fasted and fed state, with and without co-administration of a SNEDDS, with a one week wash-out period 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 a reduction of the observed food effect and an increased absorption of cinnarizine in the fasted state; based upon the individual ratios, which was not reflected in the mean data. However, the co-administration of SNEEDS in the fasted state, also induce a slower gastric emptying rate, which was observed as a delayed tmax for both cinnarizine and paracetamol. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Study on the interactions of antiemetic drugs and 12-tungstophosphoric acid by absorption and resonance Rayleigh scattering spectra and their analytical applications

    Science.gov (United States)

    Wang, Yaqiong; Liu, Shaopu; Liu, Zhongfang; Yang, Jidong; Hu, Xiaoli

    2013-03-01

    In 0.1 mol L-1 HCl medium, antiemetic drugs (ATM), such as granisetron hydrochloride (GS) and tropisetron hydrochloride (TS), reacted with H3PW12O40·nH2O and formed 3:1 ion-association complex of [(ATM)3PW12O40], then self-aggregated into nanoparticles-[(ATM)3PW12O40]n with an average size of 100 nm. The reaction resulted in the enhancement of resonance Rayleigh scattering (RRS) and the absorption spectra. The increments of scattering intensity (ΔIRRS) and the change of absorbance (ΔA) were both directly proportional to the concentrations of ATM in certain ranges. Accordingly, two new RRS and spectrophotometric methods were proposed for ATM detection. The detection limits (3σ) of GS and TS were 3.2 ng mL-1 and 4.0 ng mL-1(RRS method), 112.5 ng mL-1 and 100.0 ng mL-1(spectrophotometric method). These two methods were applied to determine GS in orally disintegrating tablets and the results were in good agreement with the official method. The ground-state geometries and electronic structures of GS and TS were optimized by the hybrid density functional theory (DFT) method and the shape of [(ATM)3PW12O40]n was characterized by atomic force microscopy (AFM). Take the RRS method with higher sensitivity as an example, the reaction mechanism and the reasons for enhancement of scattering were discussed.

  11. 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

    2013-01-01

    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 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. PMID:22589226

  12. Advances in simultaneous DSC-FTIR microspectroscopy for rapid solid-state chemical stability studies: some dipeptide drugs as examples.

    Science.gov (United States)

    Lin, Shan-Yang; Wang, Shun-Li

    2012-04-01

    The solid-state chemistry of drugs has seen growing importance in the pharmaceutical industry for the development of useful API (active pharmaceutical ingredients) of drugs and stable dosage forms. The stability of drugs in various solid dosage forms is an important issue because solid dosage forms are the most common pharmaceutical formulation in clinical use. In solid-state stability studies of drugs, an ideal accelerated method must not only be selected by different complicated methods, but must also detect the formation of degraded product. In this review article, an analytical technique combining differential scanning calorimetry and Fourier-transform infrared (DSC-FTIR) microspectroscopy simulates the accelerated stability test, and simultaneously detects the decomposed products in real time. The pharmaceutical dipeptides aspartame hemihydrate, lisinopril dihydrate, and enalapril maleate either with or without Eudragit E were used as testing examples. This one-step simultaneous DSC-FTIR technique for real-time detection of diketopiperazine (DKP) directly evidenced the dehydration process and DKP formation as an impurity common in pharmaceutical dipeptides. DKP formation in various dipeptides determined by different analytical methods had been collected and compiled. Although many analytical methods have been applied, the combined DSC-FTIR technique is an easy and fast analytical method which not only can simulate the accelerated drug stability testing but also at the same time enable to explore phase transformation as well as degradation due to thermal-related reactions. This technique offers quick and proper interpretations. Copyright © 2012 Elsevier B.V. All rights reserved.

  13. 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...... availability was affected by the triglyceride incorporated into the multi-component delivery system and availabilities of 56.9% (MLM) and 37.2% (LML) were found. These data indicate that the pharmaceutical scientist can use the structure of the lipid to affect the relative contribution of the two absorption...

  14. Calcium absorption

    International Nuclear Information System (INIS)

    Carlmark, B.; Reizenstein, P.; Dudley, R.A.

    1976-01-01

    The methods most commonly used to measure the absorption and retention of orally administered calcium are reviewed. Nearly all make use of calcium radioisotopes. The magnitude of calcium absorption and retention depends upon the chemical form and amount of calcium administered, and the clinical and nutritional status of the subject; these influences are briefly surveyed. (author)

  15. In vivo imaging of antileukemic drug asparaginase reveals a rapid macrophage-mediated clearance from the bone marrow

    NARCIS (Netherlands)

    Van Der Meer, Laurens T.; Terry, Samantha Y.A.; Van Ingen Schenau, Dorette S.; Andree, Kiki Carlijn; Franssen, Gerben M.; Roeleveld, Debbie M.; Metselaar, Josbert M.; Reinheckel, Thomas; Hoogerbrugge, Peter M.; Boerman, Otto C.; van Leeuwen, Frank N.

    2017-01-01

    Maxima Center for Pediatric Oncology, Utrecht, The Netherlands The antileukemic drug asparaginase, a key component in the treatment of acute lymphoblastic leukemia, acts by depleting asparagine from the blood. However, little is known about its pharmacokinetics, and mechanisms of therapy resistance

  16. Microbial receptor assay for rapid detection and identification of seven families of antimicrobial drugs in milk: collaborative study

    International Nuclear Information System (INIS)

    Charm, S.E.; Chi, R.

    1988-01-01

    A microbial competitive receptor assay for detecting residues of antibiotic families in milk was studied collaboratively by 13 laboratories. In this method, microbial cells added to a milk sample provide specific binding sites for which 14 C or 3 H labeled drug competes with drug resides in the sample. The 14 C or 3 H binding to the specific binding sites is measured in a scintillation counter and compared with a zero standard milk. If the sample is statistically different from the zero standard, it is positive. The assay takes about 15 min. The binding reaction occurs between the receptor site and the drug functional group, so all members of a drug family are detected. In this case, beta-lactams, tetracyclines, macrolides, aminoglycosides, novobiocin, chloramphenicol, and sulfonamides, including p-amino-benzoic acid (PABA) and its other analogs, are detectable. The incidence of false negative determinations among samples is about 1%; the incidence of false positives is about 3%. For negative cases, the relative standard deviations for repeatability ranged from 0 to 5% and for reproducibility from 0 to 6%. For positive cases, relative standard deviations ranged from 0 to 13% for repeatability and from 0 to 14% for reproducibility. The method has been adopted official first action

  17. 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...

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

    NARCIS (Netherlands)

    Nielen, M.W.F.; Hooijerink, H.; Claassen, F.C.; Engelen, M.C.; Beek, van T.A.

    2009-01-01

    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

  19. Absorption studies

    International Nuclear Information System (INIS)

    Ganatra, R.D.

    1992-01-01

    Absorption studies were once quite popular but hardly anyone does them these days. It is easier to estimate the blood level of the nutrient directly by radioimmunoassay (RIA). However, the information obtained by estimating the blood levels of the nutrients is not the same that can be obtained from the absorption studies. Absorption studies are primarily done to find out whether some of the essential nutrients are absorbed from the gut or not and if they are absorbed, to determine how much is being absorbed. In the advanced countries, these tests were mostly done to detect pernicious anaemia where vitamin B 12 is not absorbed because of the lack of the intrinsic factor in the stomach. In the tropical countries, ''malabsorption syndrome'' is quire common. In this condition, several nutrients like fat, folic acid and vitamin B 12 are not absorbed. It is possible to study absorption of these nutrients by radioisotopic absorption studies

  20. Rapid, simple, and highly sensitive analysis of drugs in biological samples using thin-layer chromatography coupled with matrix-assisted laser desorption/ionization mass spectrometry.

    Science.gov (United States)

    Kuwayama, Kenji; Tsujikawa, Kenji; Miyaguchi, Hajime; Kanamori, Tatsuyuki; Iwata, Yuko T; Inoue, Hiroyuki

    2012-01-01

    Rapid and precise identification of toxic substances is necessary for urgent diagnosis and treatment of poisoning cases and for establishing the cause of death in postmortem examinations. However, identification of compounds in biological samples using gas chromatography and liquid chromatography coupled with mass spectrometry entails time-consuming and labor-intensive sample preparations. In this study, we examined a simple preparation and highly sensitive analysis of drugs in biological samples such as urine, plasma, and organs using thin-layer chromatography coupled with matrix-assisted laser desorption/ionization mass spectrometry (TLC/MALDI/MS). When the urine containing 3,4-methylenedioxymethamphetamine (MDMA) without sample dilution was spotted on a thin-layer chromatography (TLC) plate and was analyzed by TLC/MALDI/MS, the detection limit of the MDMA spot was 0.05 ng/spot. The value was the same as that in aqueous solution spotted on a stainless steel plate. All the 11 psychotropic compounds tested (MDMA, 4-hydroxy-3-methoxymethamphetamine, 3,4-methylenedioxyamphetamine, methamphetamine, p-hydroxymethamphetamine, amphetamine, ketamine, caffeine, chlorpromazine, triazolam, and morphine) on a TLC plate were detected at levels of 0.05-5 ng, and the type (layer thickness and fluorescence) of TLC plate did not affect detection sensitivity. In addition, when rat liver homogenate obtained after MDMA administration (10 mg/kg) was spotted on a TLC plate, MDMA and its main metabolites were identified using TLC/MALDI/MS, and the spots on a TLC plate were visualized by MALDI/imaging MS. The total analytical time from spotting of intact biological samples to the output of analytical results was within 30 min. TLC/MALDI/MS enabled rapid, simple, and highly sensitive analysis of drugs from intact biological samples and crude extracts. Accordingly, this method could be applied to rapid drug screening and precise identification of toxic substances in poisoning cases and

  1. A rapid alternative to X-ray crystallography for chiral determination: case studies of vibrational circular dichroism (VCD) to advance drug discovery projects.

    Science.gov (United States)

    Wesolowski, Steven S; Pivonka, Don E

    2013-07-15

    The absolute stereochemistry of chiral drugs is usually established via X-ray crystallography. However, vibrational circular dichroism (VCD) spectroscopy coupled with quantum mechanics simulations offers a rapid alternative to crystallography and is readily applied to both crystalline and non-crystalline samples. VCD is an effective complement to X-ray analysis of drug candidates, and it can be used as a high-throughput means of assessing absolute stereochemistry at all phases of the discovery process (hundreds of assignments per year). The practical implementation (or fee-for-service outsourcing) of VCD and selected case studies are illustrated with an emphasis on providing utility and impact to pharmaceutical discovery programs. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Rapid brain death caused by a cerebellar abscess with Fusobacterium nucleatum in a young man with drug abuse: a case report.

    Science.gov (United States)

    Hischebeth, Gunnar T R; Keil, Vera C; Gentil, Katrin; Boström, Azize; Kuchelmeister, Klaus; Bekeredjian-Ding, Isabelle

    2014-06-10

    Fusobacterium nucleatum is a strict anaerobic microorganism that causes disease entities such as periodontal and soft tissue abscesses, pulmonary and intraabdominal infections and very rarely intracerebral infections. Here, we report the rare case of a previously healthy 25-year-old German man with a cerebellar abscess caused by Fusobacterium nucleatum that resulted in rapid brain death. Toxicological screening showed positivity for amphetamines and cannabis. The diagnosis was obtained by polymerase chain reaction amplification of bacterial deoxyribonucleic acid in cerebrospinal fluid. In drug users clinicians should think about rare causes of brain abscesses/meningitis. Early diagnosis is necessary and justifies the use of molecular techniques.

  3. A rapid culture system uninfluenced by an inoculum effect increases reliability and convenience for drug susceptibility testing of Mycobacterium tuberculosis.

    Science.gov (United States)

    Jung, Yong-Gyun; Kim, Hyejin; Lee, Sangyeop; Kim, Suyeoun; Jo, EunJi; Kim, Eun-Geun; Choi, Jungil; Kim, Hyun Jung; Yoo, Jungheon; Lee, Hye-Jeong; Kim, Haeun; Jung, Hyunju; Ryoo, Sungweon; Kwon, Sunghoon

    2018-06-05

    The Disc Agarose Channel (DAC) system utilizes microfluidics and imaging technologies and is fully automated and capable of tracking single cell growth to produce Mycobacterium tuberculosis (MTB) drug susceptibility testing (DST) results within 3~7 days. In particular, this system can be easily used to perform DSTs without the fastidious preparation of the inoculum of MTB cells. Inoculum effect is one of the major problems that causes DST errors. The DAC system was not influenced by the inoculum effect and produced reliable DST results. In this system, the minimum inhibitory concentration (MIC) values of the first-line drugs were consistent regardless of inoculum sizes ranging from ~10 3 to ~10 8 CFU/mL. The consistent MIC results enabled us to determine the critical concentrations for 12 anti-tuberculosis drugs. Based on the determined critical concentrations, further DSTs were performed with 254 MTB clinical isolates without measuring an inoculum size. There were high agreement rates (96.3%) between the DAC system and the absolute concentration method using Löwenstein-Jensen medium. According to these results, the DAC system is the first DST system that is not affected by the inoculum effect. It can thus increase reliability and convenience for DST of MTB. We expect that this system will be a potential substitute for conventional DST systems.

  4. Folate absorption

    International Nuclear Information System (INIS)

    Baker, S.J.

    1976-01-01

    Folate is the generic term given to numerous compounds of pteroic acid with glutamic acid. Knowledge of absorption is limited because of the complexities introduced by the variety of compounds and because of the inadequacy of investigational methods. Two assay methods are in use, namely microbiological and radioactive. Techniques used to study absorption include measurement of urinary excretion, serum concentration, faecal excretion, intestinal perfusion, and haematological response. It is probably necessary to test absorption of both pteroylmonoglutamic acid and one or more polyglutamates, and such tests would be facilitated by availability of synthesized compounds labelled with radioactive tracers at specifically selected sites. (author)

  5. A luciferase-based assay for rapid assessment of drug activity against Mycobacterium tuberculosis including monitoring of macrophage viability.

    Science.gov (United States)

    Larsson, Marie C; Lerm, Maria; Ängeby, Kristian; Nordvall, Michaela; Juréen, Pontus; Schön, Thomas

    2014-11-01

    The intracellular (IC) effect of drugs against Mycobacterium tuberculosis (Mtb) is not well established but increasingly important to consider when combining current and future multidrug regimens into the best possible treatment strategies. For this purpose, we developed an IC model based on a genetically modified Mtb H37Rv strain, expressing the Vibrio harvei luciferase (H37Rv-lux) infecting the human macrophage like cell line THP-1. Cells were infected at a low multiplicity of infection (1:1) and subsequently exposed to isoniazid (INH), ethambutol (EMB), amikacin (AMI) or levofloxacin (LEV) for 5days in a 96-well format. Cell viability was evaluated by Calcein AM and was maintained throughout the experiment. The number of viable H37Rv-lux was determined by luminescence and verified by a colony forming unit analysis. The results were compared to the effects of the same drugs in broth cultures. AMI, EMB and LEV were significantly less effective intracellularly (MIC90: >4mg/L, 8mg/L and 2mg/L, respectively) compared to extracellularly (MIC90: 0.5mg/L for AMI and EMB; 0.25mg/L for LEV). The reverse was the case for INH (IC: 0.064mg/L vs EC: 0.25mg/L). In conclusion, this luciferase based method, in which monitoring of cell viability is included, has the potential to become a useful tool while evaluating the intracellular effects of anti-mycobacterial drugs. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Highly sensitive capillary electrophoresis-mass spectrometry for rapid screening and accurate quantitation of drugs of abuse in urine.

    Science.gov (United States)

    Kohler, Isabelle; Schappler, Julie; Rudaz, Serge

    2013-05-30

    The combination of capillary electrophoresis (CE) and mass spectrometry (MS) is particularly well adapted to bioanalysis due to its high separation efficiency, selectivity, and sensitivity; its short analytical time; and its low solvent and sample consumption. For clinical and forensic toxicology, a two-step analysis is usually performed: first, a screening step for compound identification, and second, confirmation and/or accurate quantitation in cases of presumed positive results. In this study, a fast and sensitive CE-MS workflow was developed for the screening and quantitation of drugs of abuse in urine samples. A CE with a time-of-flight MS (CE-TOF/MS) screening method was developed using a simple urine dilution and on-line sample preconcentration with pH-mediated stacking. The sample stacking allowed for a high loading capacity (20.5% of the capillary length), leading to limits of detection as low as 2 ng mL(-1) for drugs of abuse. Compound quantitation of positive samples was performed by CE-MS/MS with a triple quadrupole MS equipped with an adapted triple-tube sprayer and an electrospray ionization (ESI) source. The CE-ESI-MS/MS method was validated for two model compounds, cocaine (COC) and methadone (MTD), according to the Guidance of the Food and Drug Administration. The quantitative performance was evaluated for selectivity, response function, the lower limit of quantitation, trueness, precision, and accuracy. COC and MTD detection in urine samples was determined to be accurate over the range of 10-1000 ng mL(-1) and 21-1000 ng mL(-1), respectively. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. 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

    International Nuclear Information System (INIS)

    Hernandez, Felix; Bijlsma, Lubertus; Sancho, Juan V.; Diaz, Ramon; Ibanez, Maria

    2011-01-01

    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 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.

  8. 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.

  9. Rapid Globalization of Medical Device Clinical Development Programs in Japan - The Case of Drug-Eluting Stents.

    Science.gov (United States)

    Murakami, Madoka; Suzuki, Yuka; Tominaga, Toshiyoshi

    2018-02-23

    Delays in the introduction to the Japanese market of drug-eluting stents (DES) developed overseas (i.e., "device lag") decreased sharply between 2004 and 2012. The reduction accompanied a shift in clinical development from a succession pattern (initial product development and approval overseas followed by eventual entrance into the Japanese market) to parallel development (employing multiregional clinical trials (MRCTs)). Although resource-intensive in the short-term, MRCTs are proving to be an effective tool in simultaneous global product development. Creative study designs and the absence of significant ethnic differences in Japanese subjects regarding DES safety and efficacy and the pharmacokinetic behavior of their coating drugs propel this process. More general factors such as medical need and industry incentivization also encourage this shift. Physicians' preference for DES over other percutaneous coronary interventions, the expanding global DES market, and streamlined development and approval prospects each motivate industry to continue investing in DES product development. The efforts of various stakeholders were also integral to overcoming practical obstacles, and contributions by 'Harmonization by Doing' and a premarket collaboration initiative between the USA and Japan were particularly effective. Today, USA/Japan regulatory cooperation is routine, and Japan is now integrated into global medical device development. MRCTs including Japanese subjects, sites, and investigators are now commonplace.

  10. Commercial herbal medicines used as African traditional medicines: Ngoma Herbal Tonic Immune Booster interferes with a rapid urine drug screening test.

    Science.gov (United States)

    Mothibe, M E; Osuch, E; Kahler-Venter, C P

    2017-08-25

    The prevalent use of African traditional medicine by the general public has been reported. With commercialisation and marketing, some of the herbal medicines (HMs) used are readily available over the counter, most of them promoted as immune boosters. These commercial HMs have not been taken through clinical trials and other tests that would validate their composition and safety, and other properties such as their effect on laboratory diagnostic tests. To investigate the cross-reactivity of selected HMs with commonly tested drugs of abuse (DoA) using a qualitative rapid urinalysis assay. The six HMs selected were bought from local pharmacies. A rapid urinalysis screening test was performed with the Instant View Multi-Drug of Abuse Test kit from Labstix Diagnostics. Drug-free urine (DFU) was pooled from samples donated by healthy volunteers. Urine samples that had tested positive for DoA were obtained from a pharmacology laboratory. Aliquots of the urine samples were spiked with the HMs in neat and diluted form, and tested at various time intervals. The results for the DFU samples spiked with the HMs remained negative. There were no significant changes in pH or specific gravity of the samples. The results of samples that had tested positive for tetrahydrocannabinol (THC) were not altered by five of the HMs when spiked at 40% v/v. The HM Ngoma Herbal Tonic Immune Booster caused false-negative results for the THC test. An important finding is that the herbal mixture Ngoma Herbal Tonic Immune Booster caused false-negative results for the cannabinoid screening test. It adds to the list of substances that may be potential adulterants of urine for screening tests.

  11. 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.

  12. Rapid determination of some psychotropic drugs in complex matrices by tandem dispersive liquid-liquid microextraction followed by high performance liquid chromatography.

    Science.gov (United States)

    Asghari, Alireza; Fahimi, Ebrahim; Bazregar, Mohammad; Rajabi, Maryam; Boutorabi, Leila

    2017-05-01

    Simple and rapid determinations of some psychotropic drugs in some pharmaceutical wastewater and human plasma samples were successfully accomplished via the tandem dispersive liquid-liquid microextraction combined with high performance liquid chromatography-ultraviolet detection (TDLLME-HPLC-UV). TDLLME of the three psychotropic drugs clozapine, chlorpromazine, and thioridazine was easily performed through two consecutive dispersive liquid-liquid microextractions. By performing this convenient method, proper sample preconcentrations and clean-ups were achieved in just about 7min. In order to achieve the best extraction efficiency, the effective parameters involved were optimized. The optimal experimental conditions consisted of 100μL of CCl 4 (as the extraction organic solvent), and the pH values of 13 and 2 for the donor and acceptor phases, respectively. Under these optimum experimental conditions, the proposed TDLLME-HPLC-UV technique provided a good linearity in the range of 5-3000ngmL -1 for the three psychotropic drugs with the correlation of determinations (R 2 s) higher than 0.996. The limits of quantification (LOQs) and limits of detection (LODs) obtained were 5.0ngmL -1 and 1.0-1.5ngmL -1 , respectively. Also the proper enrichment factors (EFs) of 96, 99, and 88 for clozapine, chlorpromazine, and thioridazine, respectively, and good extraction repeatabilities (relative standard deviations below 9.3%, n=5) were obtained. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Drug Addiction

    Science.gov (United States)

    ... as hearing colors Impulsive behavior Rapid shifts in emotions Permanent mental changes in perception Rapid heart rate ... Drug use can negatively affect academic performance and motivation to excel in school. Legal issues. Legal problems ...

  14. Detection of drugs of abuse in exhaled breath using a device for rapid collection: comparison with plasma, urine and self-reporting in 47 drug users.

    Science.gov (United States)

    Beck, Olof; Stephanson, Niclas; Sandqvist, Sören; Franck, Johan

    2013-06-01

    Exhaled breath has recently been identified as a matrix for the detection of drugs of abuse. This work aims to further document this application using a new and simple collection device in patients following recovery from acute intoxication. Breath, plasma and urine samples were collected from 47 patients (38 males, age range 25-74) together with interview data. Analysis of breath and plasma samples was done by liquid chromatography-mass spectrometry methods. Urine was screened using immunochemical reagents and positive findings confirmed with liquid chromatography-mass spectrometry methods. The 12 analytes investigated were: methadone, amphetamine, methamphetamine, 6-acetylmorphine, morphine, benzoylecgonine, cocaine, diazepam, oxazepam, alprazolam, buprenorphine and tetrahydrocannabinol. In all 47 cases, recent intake of an abused substance prior to admission was reported, but in one case the substance (ketobemidone) was not investigated. In 40 of the remaining cases (87%) breath analysis gave a positive finding of any of the substances that were part of the analytical investigation. Identifications were based on correct chromatographic retention time and product ion ratios obtained in selected reaction monitoring mode. In general, data from breath, plasma, urine and self-reporting were in good agreement, but in 23% of the cases substances were detected that had not been self-reported. All substances covered were detected in a number of breath samples. Considering that breath sampling was often done about 24 h after intake, the detection rate was considered to be high for most substances. Analytes with low detection rates were benzodiazepines, and a further increase in analytical sensitivity is needed to overcome this. This study further supports use of exhaled breath as a new matrix in clinical toxicology.

  15. Biochemistry of drugs. XXVII

    International Nuclear Information System (INIS)

    Raz, K.; Smolik, S.; Vinarova, M.; Janda, J.; Franc, Z.

    1979-01-01

    The erythro- and threoform of p-hydroxynorephedrine belong to the group of drugs affecting the course of hypertensive disease. For pharmacological studies both forms were labelled with 3 H radionuclide on the benzene ring. 90% of radioactivity was concentrated in the ortho positions with regard to the hydroxyl, 10% in the meta position. After the administration of the labelled drug to rats, rapid absorption occurs and radioactivity is eliminated from the organism, especially in the urine. Three radioactive substances were found in the urine of experimental animals. A substance with properties corresponding to those of the administered drug prevailed. The highest levels of radioactivity in the tissues were found after intravenous administration as early as after 5 minutes after administration, 15 minutes after subcutaneous administration. It was found that p-hydroxynorephedrine significantly restricted the detainment of labelled noradrenaline-7- 3 H in the tissues of premedicated animals. (author)

  16. Rapid BAL Variability: Re-Emerging Absorption

    Energy Technology Data Exchange (ETDEWEB)

    Erakuman, Damla [Department of Astronomy and Space Sciences, Faculty of Science, Erciyes University, Kayseri (Turkey); Filiz Ak, Nurten, E-mail: damla.erakuman@gmail.com [Department of Astronomy and Space Sciences, Faculty of Science, Erciyes University, Kayseri (Turkey); Astronomy and Space Sciences Observatory and Research Center, Erciyes University, Kayseri (Turkey)

    2017-11-08

    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.

  17. Towards the development of a rapid, portable, surface enhanced Raman spectroscopy based cleaning verification system for the drug nelarabine.

    Science.gov (United States)

    Corrigan, Damion K; Salton, Neale A; Preston, Chris; Piletsky, Sergey

    2010-09-01

    Cleaning verification is a scientific and economic problem for the pharmaceutical industry. A large amount of potential manufacturing time is lost to the process of cleaning verification. This involves the analysis of residues on spoiled manufacturing equipment, with high-performance liquid chromatography (HPLC) being the predominantly employed analytical technique. The aim of this study was to develop a portable cleaning verification system for nelarabine using surface enhanced Raman spectroscopy (SERS). SERS was conducted using a portable Raman spectrometer and a commercially available SERS substrate to develop a rapid and portable cleaning verification system for nelarabine. Samples of standard solutions and swab extracts were deposited onto the SERS active surfaces, allowed to dry and then subjected to spectroscopic analysis. Nelarabine was amenable to analysis by SERS and the necessary levels of sensitivity were achievable. It is possible to use this technology for a semi-quantitative limits test. Replicate precision, however, was poor due to the heterogeneous drying pattern of nelarabine on the SERS active surface. Understanding and improving the drying process in order to produce a consistent SERS signal for quantitative analysis is desirable. This work shows the potential application of SERS for cleaning verification analysis. SERS may not replace HPLC as the definitive analytical technique, but it could be used in conjunction with HPLC so that swabbing is only carried out once the portable SERS equipment has demonstrated that the manufacturing equipment is below the threshold contamination level.

  18. 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.

  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.

    Science.gov (United States)

    Holm, René; Porter, Christopher J H; Edwards, Glenn A; Müllertz, Anette; Kristensen, Henning G; Charman, William N

    2003-09-01

    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 availability was affected by the triglyceride incorporated into the multi-component delivery system and availabilities of 56.9% (MLM) and 37.2% (LML) were found. These data indicate that the pharmaceutical scientist can use the structure of the lipid to affect the relative contribution of the two absorption pathways. The MLM formulation produced a total bioavailability of 74.9%, which is higher than the total absorption previously observed after post-prandial administration. This could indicate the utility of disperse lipid-base formulations based on structured triglycerides for the oral delivery of halofantrine, and potentially other lipophilic drugs.

  20. 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...... for isoniazid, rifampin, and ethambutol. Fifty-seven of the isolates were tested for pyrazinamide. Results were compared to those of radiometric BACTEC 460 system and discrepancies were resolved by the agar proportion method. We found an overall agreement of 99.0% for isoniazid, 99.5% for rifampin, 98.......2% for ethambutol, and 100% for pyrazinamide. After resolution of discrepancies, MGIT yielded no false susceptibility for rifampin and isoniazid. Although turnaround times were comparable, MGIT provides an advantage as inoculation can be done on any weekday as the growth is monitored automatically. The automated...

  1. 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...

  2. Investigation of clinical pharmacokinetic variability of an opioid antagonist through physiologically based absorption modeling.

    Science.gov (United States)

    Ding, Xuan; He, Minxia; Kulkarni, Rajesh; Patel, Nita; Zhang, Xiaoyu

    2013-08-01

    Identifying the source of inter- and/or intrasubject variability in pharmacokinetics (PK) provides fundamental information in understanding the pharmacokinetics-pharmacodynamics relationship of a drug and project its efficacy and safety in clinical populations. This identification process can be challenging given that a large number of potential causes could lead to PK variability. Here we present an integrated approach of physiologically based absorption modeling to investigate the root cause of unexpectedly high PK variability of a Phase I clinical trial drug. LY2196044 exhibited high intersubject variability in the absorption phase of plasma concentration-time profiles in humans. This could not be explained by in vitro measurements of drug properties and excellent bioavailability with low variability observed in preclinical species. GastroPlus™ modeling suggested that the compound's optimal solubility and permeability characteristics would enable rapid and complete absorption in preclinical species and in humans. However, simulations of human plasma concentration-time profiles indicated that despite sufficient solubility and rapid dissolution of LY2196044 in humans, permeability and/or transit in the gastrointestinal (GI) tract may have been negatively affected. It was concluded that clinical PK variability was potentially due to the drug's antagonism on opioid receptors that affected its transit and absorption in the GI tract. Copyright © 2013 Wiley Periodicals, Inc.

  3. Determination of anthelmintic drug residues in milk using ultra high performance liquid chromatography-tandem mass spectrometry with rapid polarity switching.

    Science.gov (United States)

    Whelan, Michelle; Kinsella, Brian; Furey, Ambrose; Moloney, Mary; Cantwell, Helen; Lehotay, Steven J; Danaher, Martin

    2010-07-02

    A new UHPLC-MS/MS (ultra high performance liquid chromatography coupled to tandem mass spectrometry) method was developed and validated to detect 38 anthelmintic drug residues, consisting of benzimidazoles, avermectins and flukicides. A modified QuEChERS-type extraction method was developed with an added concentration step to detect most of the analytes at keeper to ensure analytes remain in solution. Using rapid polarity switching in electrospray ionisation, a single injection was capable of detecting both positively and negatively charged ions in a 13 min run time. The method was validated at two levels: the unapproved use level and at the maximum residue level (MRL) according to Commission Decision (CD) 2002/657/EC criteria. The decision limit (CCalpha) of the method was in the range of 0.14-1.9 and 11-123 microg kg(-1) for drugs validated at unapproved and MRL levels, respectively. The performance of the method was successfully verified for benzimidazoles and levamisole by participating in a proficiency study.

  4. Reduction of the use of antimicrobial drugs following the rapid detection of Streptococcus agalactiae in the vagina at delivery by real-time PCR assay.

    Science.gov (United States)

    Poncelet-Jasserand, E; Forges, F; Varlet, M-N; Chauleur, C; Seffert, P; Siani, C; Pozzetto, B; Ros, A

    2013-08-01

    To assess whether the determination of the presence of group B streptococci (GBS) in the vagina using a rapid polymerase chain reaction (PCR) assay at delivery was able to spare useless antimicrobial treatments, as compared with conventional culture at 34-38 weeks of gestation. Practical evaluation and prospective cost-effectiveness analysis. A university hospital in France. A cohort of 225 women in labour at the University-Hospital of Saint-Etienne. Each woman had a conventional culture performed at 34-38 weeks of gestation. At the beginning of labour, two vaginal swabs were sampled for rapid PCR testing and culture. The decision to prescribe a prophylactic antimicrobial treatment or not was taken according to the result of the PCR test. A comparative cost-effectiveness analysis of the two diagnostic strategies was carried out. Number of women receiving inadequate prophylactic antimicrobial drugs following each testing strategy, costs of PCR testing and culture, frequency of vaginal GBS, and diagnostic performance of the PCR test at delivery. The percentage of unnecessarily treated women was significantly reduced using the rapid test versus conventional culture (4.5 and 13.6%, respectively; P < 0.001). The rate of vaginal GBS at delivery was 12.5%. The incremental cost-effectiveness ratio (ICER) for each inadequate management avoided was €36 and €173 from the point of view of the healthcare system and hospital, respectively. The PCR assay reduced the number of inadequate antimicrobial treatments aimed to prevent the early onset of GBS disease. However, this strategy generates extra costs that must be put into balance with its clinical benefits. © 2013 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2013 RCOG.

  5. 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.

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

    International Nuclear Information System (INIS)

    King, A.B.; Schwartz, R.

    1987-01-01

    Ethambutol, [CH 3 CH 2 -CH(CH 2 OH)-NH-CH 2 ] 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 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, 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

  7. Absorptive products

    International Nuclear Information System (INIS)

    Assarsson, P.G.; King, P.A.

    1976-01-01

    Applications for hydrophile gels produced by the radiation induced cross-linking in aqueous solution of polyethylene oxide and starch, as described in Norwegian patent 133501 (INIS RN 281494), such as sanitary napkins (diapers) and sanitary towels, are discussed. The process itself is also discussed and results, expressed as the percentage of insoluble gel and its absorptive capacity for saline solution as functions of the ratio of polyethylene oxide to starch and the radiation dose, are presented. (JIW)

  8. Artificial Lipid Membrane Permeability Method for Predicting Intestinal Drug Transport: Probing the Determining Step in the Oral Absorption of Sulfadiazine; Influence of the Formation of Binary and Ternary Complexes with Cyclodextrins.

    Science.gov (United States)

    Delrivo, Alicia; Aloisio, Carolina; Longhi, Marcela R; Granero, Gladys

    2018-04-01

    We propose an in vitro permeability assay by using a modified lipid membrane to predict the in vivo intestinal passive permeability of drugs. Two conditions were tested, one with a gradient pH (pH 5.5 donor/pH 7.4 receptor) and the other with an iso-pH 7.4. The predictability of the method was established by correlating the obtained apparent intestinal permeability coefficients (P app ) and the oral dose fraction absorbed in humans (f a ) of 16 drugs with different absorption properties. The P app values correlated well with the absorption rates under the two conditions, and the method showed high predictability and good reproducibility. On the other hand, with this method, we successfully predicted the transport characteristics of oral sulfadiazine (SDZ). Also, the tradeoff between the increase in the solubility of SDZ by its complex formation with cyclodextrins and/or aminoacids and its oral permeability was assessed. Results suggest that SDZ is transported through the gastrointestinal epithelium by passive diffusion in a pH-dependent manner. These results support the classification of SDZ as a high/low borderline permeability compound and are in agreement with the Biopharmaceutics Classification Systems (BCS). This conclusion is consistent with the in vivo pharmacokinetic properties of SDZ.

  9. 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.

  10. RApid Primary care Initiation of Drug treatment for Transient Ischaemic Attack (RAPID−TIA): study protocol for a pilot randomised controlled trial

    Science.gov (United States)

    2013-01-01

    Background People who have a transient ischaemic attack (TIA) or minor stroke are at high risk of a recurrent stroke, particularly in the first week after the event. Early initiation of secondary prevention drugs is associated with an 80% reduction in risk of stroke recurrence. This raises the question as to whether these drugs should be given before being seen by a specialist – that is, in primary care or in the emergency department. The aims of the RAPID-TIA pilot trial are to determine the feasibility of a randomised controlled trial, to analyse cost effectiveness and to ask: Should general practitioners and emergency doctors (primary care physicians) initiate secondary preventative measures in addition to aspirin in people they see with suspected TIA or minor stroke at the time of referral to a specialist? Methods/Design This is a pilot randomised controlled trial with a sub-study of accuracy of primary care physician diagnosis of TIA. In the pilot trial, we aim to recruit 100 patients from 30 general practices (including out-of-hours general practice centres) and 1 emergency department whom the primary care physician diagnoses with TIA or minor stroke and randomly assign them to usual care (that is, initiation of aspirin and referral to a TIA clinic) or usual care plus additional early initiation of secondary prevention drugs (a blood-pressure lowering protocol, simvastatin 40 mg and dipyridamole 200 mg m/r bd). The primary outcome of the main study will be the number of strokes at 90 days. The diagnostic accuracy sub-study will include these 100 patients and an additional 70 patients in whom the primary care physician thinks the diagnosis of TIA is possible, rather than probable. For the pilot trial, we will report recruitment rate, follow-up rate, a preliminary estimate of the primary event rate and occurrence of any adverse events. For the diagnostic study, we will calculate sensitivity and specificity of primary care physician diagnosis using the final

  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. Evaluation of monolithic and sub 2 microm particle packed columns for the rapid screening for illicit drugs--application to the determination of drug contamination on Irish euro banknotes.

    Science.gov (United States)

    Bones, Jonathan; Macka, Mirek; Paull, Brett

    2007-03-01

    A study comparing recently available 100 x 3 mm id, 200 x 3 mm id monolithic reversed-phase columns with a 50 x 2.1 mm id, 1.8 microm particle packed reversed-phase columns was carried out to determine the most efficient approach (using traditional van Deemter analysis and a modern kinetic plot approach) for the rapid screening of samples for 16 illicit drugs and associated metabolites. A plot of column backpressure versus plate number (N) showed a significant advantage of using the monolithic phases, with the 20 cm monolithic column exhibiting a maximum 15,000 plates at a column backpressure of approximately 70 bar, compared to approximately 7000 plates at 150 bar for the 5 cm 1.8 microm particle packed column. Optimum linear velocities were found to be 0.40 mm s(-1), 0.52 mm s(-1) and 0.98 mm s(-1) for the three above columns, respectively. The 20 cm monolithic column was subsequently applied to the separation and determination of illicit drug contamination on Irish euro banknotes, using methanol extraction followed by LC-MS/MS. Method performance data showed that the new LC-MS/MS method was significantly more sensitive than previous GC-MS/MS based methods for this application, with detection limits in the pg note(-1) region, based upon a 20 microL standard injection. All of the notes examined tested positive for trace quantities of cocaine, with benzoylecgonine detected on 12 of the 45 notes sampled. Traces of heroin were also detected on three of the 45 notes.

  13. Segmental dependent transport of low permeability compounds along the small intestine due to P-glycoprotein: the role of efflux transport in the oral absorption of BCS class III drugs.

    Science.gov (United States)

    Dahan, Arik; Amidon, Gordon L

    2009-01-01

    The purpose of this study was to investigate the role of P-gp efflux in the in vivo intestinal absorption process of BCS class III P-gp substrates, i.e. high-solubility low-permeability drugs. The in vivo permeability of two H (2)-antagonists, cimetidine and famotidine, was determined by the single-pass intestinal perfusion model in different regions of the rat small intestine, in the presence or absence of the P-gp inhibitor verapamil. The apical to basolateral (AP-BL) and the BL-AP transport of the compounds in the presence or absence of various efflux transporters inhibitors (verapamil, erythromycin, quinidine, MK-571 and fumitremorgin C) was investigated across Caco-2 cell monolayers. P-gp expression levels in the different intestinal segments were confirmed by immunoblotting. Cimetidine and famotidine exhibited segmental dependent permeability through the gut wall, with decreased P(eff) in the distal ileum in comparison to the proximal regions of the intestine. Coperfusion of verapamil with the drugs significantly increased the permeability in the ileum, while no significant change in the jejunal permeability was observed. Both drugs exhibited significantly greater BL-AP than AP-BL Caco-2 permeability, indicative of net mucosal secretion. Concentration dependent decrease of this secretion was obtained by the P-gp inhibitors verapamil, erythromycin and quinidine, while no effect was evident by the MRP2 inhibitor MK-571 and the BCRP inhibitor FTC, indicating that P-gp is the transporter mediates the intestinal efflux of cimetidine and famotidine. P-gp levels throughout the intestine were inversely related to the in vivo permeability of the drugs from the different segments. The data demonstrate that for these high-solubility low-permeability P-gp substrates, P-gp limits in vivo intestinal absorption in the distal segments of the small intestine; however P-gp plays a minimal role in the proximal intestinal segments due to significant lower P-gp expression levels

  14. A New Class III Antiarrhythmic Drug Niferidil Prolongs Action Potentials in Guinea Pig Atrial Myocardium via Inhibition of Rapid Delayed Rectifier.

    Science.gov (United States)

    Abramochkin, Denis V; Kuzmin, Vladislav S; Rosenshtraukh, Leonid V

    2017-12-01

    A new class III antiarrhythmic drug niferidil (RG-2) has been introduced as a highly effective therapy for cases of persistent atrial fibrillation, but ionic mechanisms of its action are poorly understood. In the present study, the effects of niferidil on action potential (AP) waveform and potassium currents responsible for AP repolarization were investigated in guinea pig atrial myocardium. APs were recorded with sharp glass microelectrodes in multicellular atrial preparations. Whole-cell patch-clamp technique was used to measure K + currents in isolated myocytes. In multicellular atrial preparations, 10 -8  M niferidil effectively prolonged APs by 15.2 ± 2.8% at 90% repolarization level. However, even the highest tested concentrations, 10 -6  M and 10 -5  M failed to prolong APs more than 32.5% of control duration. The estimated concentration of niferedil for half-maximal AP prolongation was 1.13 × 10 -8  M. Among the potassium currents responsible for AP repolarization phase, I K1 was found to be almost insensitive to niferidil. However, another inward rectifier, I KACh , was effectively suppressed by micromolar concentrations of niferidil with IC 50  = 9.2 × 10 -6  M. I KATP was much less sensitive to the drug with IC 50  = 2.26 × 10 -4  M. The slow component of delayed rectifier, I Ks , also demonstrated low sensitivity to niferidil-the highest used concentration, 10 -4  M, decreased peak I Ks density to 46.2 ± 5.5% of control. Unlike I Ks , the rapid component of delayed rectifier, I Kr , appeared to be extremely sensitive to niferidil. The IC 50 was 1.26 × 10 -9  M. I Kr measured in ventricular myocytes was found to be less sensitive to niferidil with IC 50  = 3.82 × 10 -8  M. Niferidil prolongs APs in guinea pig atrial myocardium via inhibition of I Kr .

  15. 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.

  16. Promises of Machine Learning Approaches in Prediction of Absorption of Compounds.

    Science.gov (United States)

    Kumar, Rajnish; Sharma, Anju; Siddiqui, Mohammed Haris; Tiwari, Rajesh Kumar

    2018-01-01

    The Machine Learning (ML) is one of the fastest developing techniques in the prediction and evaluation of important pharmacokinetic properties such as absorption, distribution, metabolism and excretion. The availability of a large number of robust validation techniques for prediction models devoted to pharmacokinetics has significantly enhanced the trust and authenticity in ML approaches. There is a series of prediction models generated and used for rapid screening of compounds on the basis of absorption in last one decade. Prediction of absorption of compounds using ML models has great potential across the pharmaceutical industry as a non-animal alternative to predict absorption. However, these prediction models still have to go far ahead to develop the confidence similar to conventional experimental methods for estimation of drug absorption. Some of the general concerns are selection of appropriate ML methods and validation techniques in addition to selecting relevant descriptors and authentic data sets for the generation of prediction models. The current review explores published models of ML for the prediction of absorption using physicochemical properties as descriptors and their important conclusions. In addition, some critical challenges in acceptance of ML models for absorption are also discussed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  17. Rectal absorption of homatropine [14C] methylbromide in the rat

    International Nuclear Information System (INIS)

    Cramer, M.B.; Cates, L.A.; Clarke, D.E.

    1978-01-01

    Homatropine [ 14 C]methylbromide (HMB- 14 C) was administered to rats by intramuscular injection, oral gavage and rectal suppository. Plasma concentrations of 14 C were measured over the subsequent 12 h. Peak plasma concentrations were higher and achieved more rapidly after rectal administration than by other routes whether HMB- 14 C was administered in a water-soluble suppository base or in aqueous solution. Twelve h after the suppositories were inserted and retained 28% of the 14 C had been excreted in the urine while 56% remained in the large intestine. Unlabelled HMB, given in rectal suppositories to anaesthetized rats, caused prompt blockade of the effects of vagal stimulation on pulse rate and of intravenous acetylcholine on blood pressure. These results confirm the rapid rectal absorption of the drug. (author)

  18. 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.

  19. 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

  20. 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

    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...... 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....

  1. 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

    : The HTP model is able to predict drug distribution during digestion of LbDDS containing poorly water soluble drugs in the same manner as the DIVL model. Thus the HTP model might prove applicable for high-throughput evaluation of LbDDS in e.g. 96 well plates or small scale dissolution equipment....... (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 Na...

  2. pH-sensitive polymeric nanoparticles to improve oral bioavailability of peptide/protein drugs and poorly water-soluble drugs.

    Science.gov (United States)

    Wang, Xue-Qing; Zhang, Qiang

    2012-10-01

    pH-sensitive polymeric nanoparticles are promising for oral drug delivery, especially for peptide/protein drugs and poorly water-soluble medicines. This review describes current status of pH-sensitive polymeric nanoparticles for oral drug delivery and introduces the mechanisms of drug release from them as well as possible reasons for absorption improvement, with emphasis on our contribution to this field. pH-sensitive polymeric nanoparticles are prepared mainly with polyanions, polycations, their mixtures or cross-linked polymers. The mechanisms of drug release are the result of carriers' dissolution, swelling or both of them at specific pH. The possible reasons for improvement of oral bioavailability include the following: improve drug stability, enhance mucoadhesion, prolong resident time in GI tract, ameliorate intestinal permeability and increase saturation solubility and dissolution rate for poorly water-soluble drugs. As for the advantages of pH-sensitive nanoparticles over conventional nanoparticles, we conclude that (1) most carriers used are enteric-coating materials and their safety has been approved. (2) The rapid dissolution or swelling of carriers at specific pH results in quick drug release and high drug concentration gradient, which is helpful for absorption. (3) At the specific pH carriers dissolve or swell, and the bioadhesion of carriers to mucosa becomes high because nanoparticles turn from solid to gel, which can facilitate drug absorption. Copyright © 2012 Elsevier B.V. All rights reserved.

  3. Why rapid urbanization process cannot improve employment absorption capacity of service industry in China – also on the interactive mode innovation between service industry development with urbanization under the background of transformation and upgrading

    OpenAIRE

    Zeng, Shi-hong; Xia, Jie-chang

    2016-01-01

    Background: China is experiencing rapid urbanization and service industrial developement. Methods: In this paper, the relationship between urbanization and service employment is studied by using mathematical model and econometric test method. Results: This paper documents that there is a significant positive correlation between rapid urbanization process and services absorbing employment ability by the regression result using time-series data since China's reform and opening up. China's urban...

  4. Transdermic absorption of Melagenina II

    International Nuclear Information System (INIS)

    Hernandez Gonzalez, I.; Martinez Lopez, B.; Ruiz Pena, M.; Caso Pena, R.

    1997-01-01

    The transdermic absorption of Melagenina II (MII) was evaluated. MII was a labelled with 125I by the yodogen method and purified by column chromatography with Sephadex LH-20 in ethanol: water (7:3). In vitro absorption of ( 125I ) - MII thought human skin was carried out in Keshary-Chien modified diffusion cells. Tape stripping method was applied after 24 hours to evaluate the accumulated activity in dermis and epidermis. In vivo assays were performed in Sprague Dawley rats to analyze absorption of MII until 24 hours after a single application and for five days a low penetrability of the drug while in vivo there were not found blood levels significantly greater than zero , nevertheless and important amount of radioactivity was found in feces and urine. The activity was concentrated mainly in the application site in both models

  5. 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.

    Directory of Open Access Journals (Sweden)

    Neeraj Raizada

    Full Text Available 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

  6. In vivo analysis of supersaturation/precipitation/absorption behavior after oral administration of pioglitazone hydrochloride salt; determinant site of oral absorption.

    Science.gov (United States)

    Tanaka, Yusuke; Sugihara, Masahisa; Kawakami, Ayaka; Imai, So; Itou, Takafumi; Murase, Hirokazu; Saiki, Kazunori; Kasaoka, Satoshi; Yoshikawa, Hiroshi

    2017-08-30

    The purpose of this study was to evaluate in vivo supersaturation/precipitation/absorption behavior in the gastrointestinal (GI) tract based on the luminal concentration-time profiles after oral administration of pioglitazone (PG, a highly permeable lipophilic base) and its hydrochloride salt (PG-HCl) to rats. In the in vitro precipitation experiment in the classic closed system, while the supersaturation was stable in the simulated gastric condition, PG drastically precipitated in the simulated intestinal condition, particularly at a higher initial degree of supersaturation. Nonetheless, a drastic and moderate improvement in absorption was observed in vivo at a low and high dose of PG-HCl, respectively. Analysis based on the luminal concentration of PG after oral administration of PG-HCl at a low dose revealed that most of the dissolved PG emptied from the stomach was rapidly absorbed before its precipitation in the duodenum. At a high dose of PG-HCl, PG partly precipitated in the duodenum but was absorbed to some extent. Therefore, the extent of the absorption was mainly dependent on the duodenal precipitation behavior. Furthermore, a higher-than expected absorption after oral administration of PG-HCl from in vitro precipitation study may be due to the absorption process in the small intestine, which suppresses the precipitation by removal of the drug. This study successfully clarify the impact of the absorption process on the supersaturation/precipitation/absorption behavior and key absorption site for a salt formulation of a highly permeable lipophilic base based on the direct observation of in vivo luminal concentration. Our findings may be beneficial in developing an ideal physiologically based pharmacokinetic model and in vitro predictive dissolution tools and/or translating the in silico and in vitro data to the in vivo outcome. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. The determination of sulphur in materials of high neutron absorption cross-section by fast-neutron activation analysis; Determination du soufre dans les matieres de forte section efficace d'absorption neutronique, au moyen d'une analyse par activation avec des neutrons rapides; Opredelenie sery v materialakh s bol'shim secheniem pogloshcheniya nejtronov metodom aktivatsionnogo analiza bystrykh nejtronov; Determinacion del azufre en sustancias de elevada seccion eficaz de absorcion neutronica mediante analisis por activacion con neutrones rapidos

    Energy Technology Data Exchange (ETDEWEB)

    Gibbons, D; Simpson, H [Wantage Research Laboratory (A.E.R.E.), Wantage, Berks. (United Kingdom)

    1962-01-15

    The production of radiophosphorus by the fast neutron (n, p) reaction on sulphur is used for the determination of sulphur by activation analysis. Using this technique it is possible to determine sulphur in materials of high thermal-neutron absorption cross-section because the absorption cross-sections for fast neutrons are, in general, much lower than those for slow neutrons, so that self-shielding errors are considerably reduced. Interference due to the slow neutron (n, {gamma}) reaction on neutral phosphorus is eliminated by a double irradiation technique involving irradiation in regions of differing slow/fast flux-ratios. The method has been applied to the determination of sulphur in chromium and arsenic. (author) [French] La production de radiophosphore par reaction (n, p) de neutrons rapides sur le soufre est utilisee pour la determination du soufre au moyen d'une analyse par activation. Cette methode permet la determination du soufre dans les matieres de forte section efficace d'absorption des neutrons thermiques; en effet, les sections efficaces d'absorption des neutrons rapides sont, d'une maniere generale, beaucoup plus faibles que pour les neutrons lents, de sorte que les erreurs d'autoprotection se trouvent considerablement reduites. L'interference due a la reaction (n, {gamma}) des neutrons lents sur le phosphore naturel est eliminee par une double irradiation, qui implique une irradiation dans les regions ou le rapport du flux de neutrons lents au flux de neutrons rapides a des valeurs differentes. La methode a ete appliquee a la determination du soufre dans le chrome et l'arsenic. (author) [Spanish] La formacion de fosforo radiactivo por la accion de los neutrones rapidos sobre el azufre, reaccion (n, p), puede servir para determinar este elemento mediante analisis por activacion. El empleo de esta tecnica permite efectuar determinaciones de azufre en materiales de elevada seccion eficaz de absorcion de neutrones termicos porque, en general, las

  8. Rectal drug administration: clinical pharmacokinetic considerations.

    Science.gov (United States)

    de Boer, A G; Moolenaar, F; de Leede, L G; Breimer, D D

    1982-01-01

    The human rectum represents a body cavity in which drugs can be easily introduced and retained and from which absorption is well possible. There are important therapeutic reasons why it is sometimes preferable to give a drug rectally rather than orally, e.g. in cases of nausea and vomiting. Drawbacks of rectal drug administration include the interruption of absorption by defaecation and lack of patient acceptability. The mechanism of drug absorption from the rectum is probably no different to that in the upper part of the gastrointestinal tract, despite the fact that the physiological circumstances (e.g. pH, fluid content) differ substantially, Absorption from aqueous and alcoholic solutions may occur very rapidly, which has proved to be of considerable therapeutic value in the rapid suppression of acute convulsive attacks by diazepam (e.g. in children), but absorption from suppositories is generally slower and very much dependent on the nature of the suppository base, the use of surfactants or other additives, particle size of the active ingredient, etc. There is some evidence that hepatic first-pass elimination of high clearance drugs is partially avoided after rectal administration, e.g. lignocaine. This can be explained by the rectal venous blood supply: the upper part is connected with the portal system, whereas the lower part is directly connected with the systemic circulation. Plasma concentration data following rectal administration of representatives of several classes of drugs are reviewed: anticonvulsants, non-narcotic analgesics and non-steroidal anti-inflammatory agents, hypnosedatives and anaesthetics, strong analgesics, theophylline and derivatives, corticosteroids, antibacterial agents, thiazinamium, promethazine, hyoscine-N-butyl-bromide, streptokinase, progesterone, ergotamine tartrate and levodopa. Only limited number of cases has it been adequately shown that the rectal route of administration gives plasma concentrations which are comparable to

  9. Single-Use Poly(etheretherketone) Solid-Phase Microextraction-Transmission Mode Devices for Rapid Screening and Quantitation of Drugs of Abuse in Oral Fluid and Urine via Direct Analysis in Real-Time Tandem Mass Spectrometry.

    Science.gov (United States)

    Vasiljevic, Tijana; Gómez-Ríos, Germán Augusto; Pawliszyn, Janusz

    2018-01-02

    The analysis of oral fluid (OF) and urine samples to detect drug consumption has garnered considerable attention as alternative biomatrices. Efficient implementation of microextraction and ambient ionization technologies for rapid detection of target compounds in such biomatrices creates a need for biocompatible devices which can be implemented for in vivo sampling and easily interfaced with mass spectrometry (MS) analyzers. This study introduces a novel solid-phase microextraction-transmission mode (SPME-TM) device made of poly(etheretherketone) (PEEK) mesh that can rapidly detect prohibited substances in biofluids via direct analysis in real-time tandem MS (DART-MS/MS). PEEK mesh was selected due to its biocompatibility, excellent resistance to various organic solvents, and its ability to withstand relatively high temperatures (≤350 °C). The meshes were coated with hydrophilic-lipophilic-balance particle-poly(acrylonitrile) (HLB-PAN) slurry. The robustness of the coated meshes was tested by performing rapid vortex agitation (≥3200 rpm) in LC/MS-grade solvents and by exposing them to the DART source jet stream at typical operational temperatures (∼250-350 °C). PEEK SPME-TM devices proved to be robust and were therefore used to perform ex vivo analysis of drugs of abuse spiked in urine and OF samples. Excellent results were obtained for all analytes under study; furthermore, the tests yielded satisfactory limits of quantitation (median, ∼0.5 ng mL -1 ), linearity (≥0.99), and accuracy (80-120%) over the evaluated range (0.5-200 ng mL -1 ). This research highlights plastic SPME-TM's potential usefulness as a method for rapidly screening for prohibited substances in on-site/in vivo scenarios, such as roadside or workplace drug testing, antidoping controls, and pain management programs.

  10. Regional drug user services in times of scarce financial resources: using a rapid assessment response approach to evaluate, plan, and prioritize essential services.

    Science.gov (United States)

    Comiskey, Catherine Maria; O'Sullivan, Karin; Milnes, Jennie

    2012-02-01

    The objective was to assess need, evaluate projects, and devise a roadmap for future provision given budget cuts. The analysis of 30 substance misuse services in towns and rural areas of Ireland was conducted in 2010. Analysis revealed that 24,315 (95% CI 12,928-40,629) individuals were using illegal drugs in 2006, 893 individuals were using opiates, opiate and cocaine use was increasing as was drug use amongst females. Evaluations demonstrated that not all services were meeting emerging needs, services lacked administrative support, and funding needed to be redirected. The RAR approach was useful for policy decisions and budget cuts in times of economic restraint.

  11. What Is in Your Wallet? Quantitation of Drugs of Abuse on Paper Currency with a Rapid LC-MS/MS Method

    Science.gov (United States)

    Parker, Patrick D.; Beers, Brandon; Vergne, Matthew J.

    2017-01-01

    Laboratory experiments were developed to introduce students to the quantitation of drugs of abuse by high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). Undergraduate students were introduced to internal standard quantitation and the LC-MS/MS method optimization for cocaine. Cocaine extracted from paper currency was…

  12. Hydroxyapatite hierarchically nanostructured porous hollow microspheres: rapid, sustainable microwave-hydrothermal synthesis by using creatine phosphate as an organic phosphorus source and application in drug delivery and protein adsorption.

    Science.gov (United States)

    Qi, Chao; Zhu, Ying-Jie; Lu, Bing-Qiang; Zhao, Xin-Yu; Zhao, Jing; Chen, Feng; Wu, Jin

    2013-04-22

    Hierarchically nanostructured porous hollow microspheres of hydroxyapatite (HAP) are a promising biomaterial, owing to their excellent biocompatibility and porous hollow structure. Traditionally, synthetic hydroxyapatite is prepared by using an inorganic phosphorus source. Herein, we report a new strategy for the rapid, sustainable synthesis of HAP hierarchically nanostructured porous hollow microspheres by using creatine phosphate disodium salt as an organic phosphorus source in aqueous solution through a microwave-assisted hydrothermal method. The as-obtained products are characterized by powder X-ray diffraction (XRD), Fourier-transform IR (FTIR) spectroscopy, SEM, TEM, Brunauer-Emmett-Teller (BET) nitrogen sorptometry, dynamic light scattering (DLS), and thermogravimetric analysis (TGA). SEM and TEM micrographs show that HAP hierarchically nanostructured porous hollow microspheres consist of HAP nanosheets or nanorods as the building blocks and DLS measurements show that the diameters of HAP hollow microspheres are within the range 0.8-1.5 μm. The specific surface area and average pore size of the HAP porous hollow microspheres are 87.3 m(2) g(-1) and 20.6 nm, respectively. The important role of creatine phosphate disodium salt and the influence of the experimental conditions on the products were systematically investigated. This method is facile, rapid, surfactant-free and environmentally friendly. The as-prepared HAP porous hollow microspheres show a relatively high drug-loading capacity and protein-adsorption ability, as well as sustained drug and protein release, by using ibuprofen as a model drug and hemoglobin (Hb) as a model protein, respectively. These experiments indicate that the as-prepared HAP porous hollow microspheres are promising for applications in biomedical fields, such as drug delivery and protein adsorption. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Clinical Pharmacokinetics of Systemically Administered Antileishmanial Drugs

    NARCIS (Netherlands)

    Kip, Anke E; Schellens, Jan H M; Beijnen, Jos H; Dorlo, Thomas P C

    This review describes the pharmacokinetic properties of the systemically administered antileishmanial drugs pentavalent antimony, paromomycin, pentamidine, miltefosine and amphotericin B (AMB), including their absorption, distribution, metabolism and excretion and potential drug-drug interactions.

  14. 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 ...

  15. Drug-induced thrombocytopenia

    DEFF Research Database (Denmark)

    Pedersen-Bjergaard, U; Andersen, M; Hansen, P B

    1997-01-01

    induced by non-cytotoxic drugs is characterised by heterogeneous clinical picture and recovery is generally rapid. Although corticosteroids seem inefficient, we still recommend that severe symptomatic cases of drug-induced thrombocytopenia are treated as idiopathic thrombocytopenic purpura due...

  16. Rapid screening of non-steroidal anti-inflammatory drugs illegally added in anti-rheumatic herbal supplements and herbal remedies by portable ion mobility spectrometry.

    Science.gov (United States)

    Li, Mengjiao; Ma, Haiyan; Gao, Jinglin; Zhang, Lina; Wang, Xinyu; Liu, Di; Bian, Jing; Jiang, Ye

    2017-10-25

    In this work, for the first time, a high-performance ion mobility spectrometry with electrospray ionization (ESI-HPIMS) method has been employed as a rapid screening tool for the detection of acetaminophen, ibuprofen, naproxen, diclofenac sodium and indomethacin illegally added in anti-rheumatic herbal supplements and herbal remedies. Samples were dissolved and filtered through a 0.45μm microporous membrane, then the filtrate was directly injected into the high-performance ion mobility spectrometry for analysis. Using this approach, the screening of illegal additions can be accomplished in as rapid as two to three minutes with no pretreatment required. The proposed method provided a LOD of 0.06-0.33μgmL -1 , as well as a good seperation of the five NSAIDs. The precision of the method was 0.1-0.4% (repeatability, n=6) and 0.9-3.3% (reproducibility, n=3). The proposed method appeared to be simple, rapid and highly specific, thus could be effective for the in-situ screening of NSAIDs in anti-rheumatic herbal supplements and herbal remedies. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Absorption and excretion tests

    International Nuclear Information System (INIS)

    Berberich, R.

    1988-01-01

    The absorption and excretion of radiopharmaceuticals is still of interest in diagnostic investigations of nuclear medicine. In this paper the most common methods of measuring absorption and excretion are described. The performance of the different tests and their standard values are discussed. More over the basic possibilities of measuring absorption and excretion including the needed measurement equipments are presented. (orig.) [de

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

    Science.gov (United States)

    Mullapudi, Venkata Balarama Krishna; Dheram, Karunasagar

    2018-01-01

    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% Na 2 CO 3 in just 5 minutes of UV irradiation, which can be considered an important aspect considering the difficulties involved in the cleavage of the CF 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. Copyright © 2016. Published by Elsevier B.V.

  19. 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.

  20. Calcium absorption and achlorhydria

    International Nuclear Information System (INIS)

    Recker, R.R.

    1985-01-01

    Defective absorption of calcium has been thought to exist in patients with achlorhydria. The author compared absorption of calcium in its carbonate form with that in a pH-adjusted citrate form in a group of 11 fasting patients with achlorhydria and in 9 fasting normal subjects. Fractional calcium absorption was measured by a modified double-isotope procedure with 0.25 g of calcium used as the carrier. Mean calcium absorption (+/- S.D.) in the patients with achlorhydria was 0.452 +/- 0.125 for citrate and 0.042 +/- 0.021 for carbonate (P less than 0.0001). Fractional calcium absorption in the normal subjects was 0.243 +/- 0.049 for citrate and 0.225 +/- 0.108 for carbonate (not significant). Absorption of calcium from carbonate in patients with achlorhydria was significantly lower than in the normal subjects and was lower than absorption from citrate in either group; absorption from citrate in those with achlorhydria was significantly higher than in the normal subjects, as well as higher than absorption from carbonate in either group. Administration of calcium carbonate as part of a normal breakfast resulted in completely normal absorption in the achlorhydric subjects. These results indicate that calcium absorption from carbonate is impaired in achlorhydria under fasting conditions. Since achlorhydria is common in older persons, calcium carbonate may not be the ideal dietary supplement

  1. Colloidal drug delivery system: amplify the ocular delivery.

    Science.gov (United States)

    Ali, Javed; Fazil, Mohd; Qumbar, Mohd; Khan, Nazia; Ali, Asgar

    2016-01-01

    The ocular perceivers are the most voluntarily accessible organs in terms of location in the body, yet drug distribution to these tissues is one of the most intriguing and challenging endeavors and problematic to the pharmaceutical scientist. The most of ocular diseases are treated with topical application of conventional formulation, i.e. solutions, suspensions and ointment. Typically on installation of these conventional formulations, only <5% of the applied dose penetrates the cornea and reaches intraocular tissues, while a major fraction of the instilled dose is wastage due to the presence of many ocular barriers like external barriers, rapid loss of the instilled solution from the precorneal area and nasolacrimal drainage system. Systemic absorption caused systemic side effects varying from mild to life-threatening events. The main objective of this review is to explore the role of colloidal delivery of drug to minimize the drawbacks associated with them. This review provides an insight into the various constraints associated with ocular drug delivery, summarizes recent findings and applications of colloidal delivery systems, i.e. nanoparticles, nanosuspensions, liposomes, niosomes, dendrimers and contact lenses containing nanoparticles have the capacity to distribute ocular drugs to categorical target sites and hold promise to revolutionize the therapy of many ocular perceiver diseases and minimized the circumscription of conventional delivery. Form the basis of literature review, it has been found that the novel delivery system have greater impact to maximize ocular drug absorption, and minimize systemic absorption and side effects.

  2. [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.

  3. Optimization of Flame Atomic Absorption Spectrometry for ...

    African Journals Online (AJOL)

    Optimization of Flame Atomic Absorption Spectrometry for Measurement of High Concentrations of Arsenic and Selenium. ... This procedure allowed a rapid determination of As from minimum 4.462 mg/L to higher concentrations without sample pretreatment. Besides As, this method successfully measured Se concentrations ...

  4. Absorption heat pumps

    International Nuclear Information System (INIS)

    Formigoni, C.

    1998-01-01

    A brief description of the difference between a compression and an absorption heat pump is made, and the reasons why absorption systems have spread lately are given. Studies and projects recently started in the field of absorption heat pumps, as well as criteria usually followed in project development are described. An outline (performance targets, basic components) of a project on a water/air absorption heat pump, running on natural gas or LPG, is given. The project was developed by the Robur Group as an evolution of a water absorption refrigerator operating with a water/ammonia solution, which has been on the market for a long time and recently innovated. Finally, a list of the main energy and cost advantages deriving from the use of absorption heat pumps is made [it

  5. Insulin analogues with improved absorption characteristics.

    Science.gov (United States)

    Brange, J; Hansen, J F; Langkjaer, L; Markussen, J; Ribel, U; Sørensen, A R

    1992-01-01

    The insulin preparations available today are not ideal for therapy as s.c. injection does not provide a physiological insulin profile. With the aim to improve the absorption properties recombinant DNA technology has been utilized to design novel insulin molecules with changed physico-chemical characteristics and hence altered subcutaneous absorption kinetics. Soluble, long-acting human insulin analogues in which the isoelectric point has been increased from 5.4 to approx. 7 are absorbed very slowly, providing a more constant basal insulin delivery with lower day-to-day variation than present protracted preparations. In addition they have better storage stability. Rapid-acting human insulin analogues with largely reduced self-association are absorbed substantially faster from subcutaneous tissue than current regular insulin and thus are better suited for bolus injection. The absorption kinetics of these analogues have been able to explain the mechanism behind the dose effect on insulin absorption rate.

  6. 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.

  7. 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.

  8. Threshold nonlinear absorption in Zeeman transitions

    International Nuclear Information System (INIS)

    Narayanan, Andal; Hazra, Abheera; Sandhya, S N

    2010-01-01

    We experimentally study the absorption spectroscopy from a collection of gaseous 87 Rb atoms at room temperature irradiated with three fields. Two of these fields are in a pump-probe saturation absorption configuration. The third field co-propagates with the pump field. The three fields address Zeeman degenerate transitions between hyperfine levels 5S 1/2 , F = 1 and 5P 3/2 , F = 0, F = 1 around the D2 line. We find a sub-natural absorption resonance in the counter-propagating probe field for equal detunings of all three fields. This absorption arises in conjunction with the appearance of increased transmission due to electro-magnetically induced transparency in the co-propagating fields. The novel feature of this absorption is its onset only for the blue of 5P 3/2 , F = 0, as the laser frequency is scanned through the excited states 5P 3/2 , F = 0, F = 1 and F = 2. The absorption rapidly rises to near maximum values within a narrow band of frequency near 5P 3/2 , F = 0. Our experimental results are compared with a dressed atom model. We find the threshold absorption to be a result of coherent interaction between the dressed states of our system.

  9. Enhanced vaginal drug delivery through the use of hypotonic formulations that induce fluid uptake

    Science.gov (United States)

    Ensign, Laura M.; Hoen, Timothy; Maisel, Katharina; Cone, Richard; Hanes, Justin

    2013-01-01

    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 muco-inert nanoparticles (mucus-penetrating particles, or MPP), but not conventional mucoadhesive nanparticles (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. PMID:23769419

  10. 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.

  11. Antineoplastic Drugs

    Science.gov (United States)

    Sadée, Wolfgang; El Sayed, Yousry Mahmoud

    The limited scope of therapeutic drug-level monitoring in cancer chemotherapy results from the often complex biochemical mechanisms that contribute to antineoplastic activity and obscure the relationships among drug serum levels and therapeutic benefits. Moreover, new agents for cancer chemotherapy are being introduced at a more rapid rate than for the treatment of other diseases, although the successful application of therapeutic drug-level monitoring may require several years of intensive study of the significance of serum drug levels. However, drug level monitoring can be of considerable value during phase I clinical trials of new antineoplastic agents in order to assess drug metabolism, bioavailability, and intersubject variability; these are important parameters in the interpretation of clinical studies, but have no immediate benefit to the patient. High performance liquid chromatography (HPLC) probably represents the most versatile and easily adaptable analytical technique for drug metabolite screening (1). HPLC may therefore now be the method of choice during phase I clinical trials of antineoplastic drugs. For example, within a single week we developed an HPLC assay—using a C18 reverse-phase column, UV detection, and direct serum injection after protein precipitation—for the new radiosensitizer, misonidazole (2).

  12. Rapid manufacturing for microfluidics

    CSIR Research Space (South Africa)

    Land, K

    2012-10-01

    Full Text Available for microfluidics K. LAND, S. HUGO, M MBANJWA, L FOURIE CSIR Materials Science and Manufacturing P O Box 395, Pretoria 0001, SOUTH AFRICA Email: kland@csir.co.za INTRODUCTION Microfluidics refers to the manipulation of very small volumes of fluid.... 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...

  13. 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.

  14. 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

  15. Zeeman atomic absorption spectroscopy

    International Nuclear Information System (INIS)

    Loos-Vollebregt, M.T.C. de.

    1980-01-01

    A new method of background correction in atomic absorption spectroscopy has recently been introduced, based on the Zeeman splitting of spectral lines in a magnetic field. A theoretical analysis of the background correction capability observed in such instruments is presented. A Zeeman atomic absorption spectrometer utilizing a 50 Hz sine wave modulated magnetic field is described. (Auth.)

  16. 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.

  17. Effect of food and acid-reducing agents on the absorption of oral targeted therapies in solid tumors

    NARCIS (Netherlands)

    Willemsen, A.E.C.A.B.; Lubberman, F.J.E.; Tol, J.; Gerritsen, W.R.; Herpen, C.M.L. van; Erp, N. van

    2016-01-01

    Oral targeted therapies represent an increasingly important group of drugs within modern oncology. With the shift from intravenously to orally administered drugs, drug absorption is a newly introduced factor in drug disposition. The process of absorption can have a large effect on inter- and

  18. Drug interactions with radiopharmaceuticals

    International Nuclear Information System (INIS)

    Hesslewood, S.; Leung, E.

    1994-01-01

    Considerable information on documented drug and radiopharmaceutical interactions has been assembled in a tabular form, classified by the type of nuclear medicine study. The aim is to provide a rapid reference for nuclear medicine staff to look for such interactions. The initiation of drug chart monitoring or drug history taking of nuclear medicine patients and the reporting of such events are encouraged. (orig.)

  19. Quasar Absorption Studies

    Science.gov (United States)

    Mushotzky, Richard (Technical Monitor); Elvis, Martin

    2004-01-01

    The aim of the proposal is to investigate the absorption properties of a sample of inter-mediate redshift quasars. The main goals of the project are: Measure the redshift and the column density of the X-ray absorbers; test the correlation between absorption and redshift suggested by ROSAT and ASCA data; constrain the absorber ionization status and metallicity; constrain the absorber dust content and composition through the comparison between the amount of X-ray absorption and optical dust extinction. Unanticipated low energy cut-offs where discovered in ROSAT spectra of quasars and confirmed by ASCA, BeppoSAX and Chandra. In most cases it was not possible to constrain adequately the redshift of the absorber from the X-ray data alone. Two possibilities remain open: a) absorption at the quasar redshift; and b) intervening absorption. The evidences in favour of intrinsic absorption are all indirect. Sensitive XMM observations can discriminate between these different scenarios. If the absorption is at the quasar redshift we can study whether the quasar environment evolves with the Cosmic time.

  20. Uranium absorption study pile

    International Nuclear Information System (INIS)

    Raievski, V.; Sautiez, B.

    1959-01-01

    The report describes a pile designed to measure the absorption of fuel slugs. The pile is of graphite and comprises a central section composed of uranium rods in a regular lattice. RaBe sources and BF 3 counters are situated on either side of the center. A given uranium charge is compared with a specimen charge of about 560 kg, and the difference in absorption between the two noted. The sensitivity of the equipment will detect absorption variations of about a few ppm boron (10 -6 boron per gr. of uranium) or better. (author) [fr

  1. Total photon absorption

    International Nuclear Information System (INIS)

    Carlos, P.

    1985-06-01

    The present discussion is limited to a presentation of the most recent total photonuclear absorption experiments performed with real photons at intermediate energy, and more precisely in the region of nucleon resonances. The main sources of real photons are briefly reviewed and the experimental procedures used for total photonuclear absorption cross section measurements. The main results obtained below 140 MeV photon energy as well as above 2 GeV are recalled. The experimental study of total photonuclear absorption in the nuclear resonance region (140 MeV< E<2 GeV) is still at its beginning and some results are presented

  2. ORAL COLON TARGETED DRUG DELIVERY SYSTEM: A REVIEW ON CURRENT AND NOVEL PERSPECTIVES

    OpenAIRE

    Asija Rajesh; Chaudhari Bharat; Asija Sangeeta

    2012-01-01

    Small intestine is mostly the site for drug absorption but in some cases the drug needs to be targeted to colon due to some factors like local colonic disease, degradation related conditions, delayed release of drugs, systemic delivery of protein and peptide drugs etc. Colon targeted drug delivery is important and relatively new concept for the absorption of drugs because it offers almost neutral pH and long residence time, thereby increasing the drug absorption. Colon has proved to be a site...

  3. Absorption heat pump system

    Science.gov (United States)

    Grossman, G.

    1982-06-16

    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.

  4. Zeeman atomic absorption spectrometry

    International Nuclear Information System (INIS)

    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

  5. 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...... learning processes of absorptive capacity, which comprise combinative and adaptive capabilities. Drawing on survey data (n=169), the study concludes that combinative capabilities primarily enhance transformative and exploratory learning processes, while adaptive capabilities strengthen all three learning...

  6. Comment on resonant absorption

    International Nuclear Information System (INIS)

    Hammerling, P.

    1977-01-01

    An average over angles of incidence of the usual resonant absorption function is presented. This form is appropriate under experimental conditions where the angles of incidence vary greatly and in an unknown manner. For comparison a lens-ellipsoidal mirror illumination system with a known longitudinal aberration is considered. In the latter example the angles of incidence are readily obtained and the resulting resonance absorption function evaluated. The associated fields are calculated in a similar fashion. (author)

  7. Optical absorption measurement system

    International Nuclear Information System (INIS)

    Draggoo, V.G.; Morton, R.G.; Sawicki, R.H.; Bissinger, H.D.

    1989-01-01

    This patent describes 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

  8. Rapid chemical analysis of allanite

    International Nuclear Information System (INIS)

    Nishiyama, Goro; Hayashi, Hiroshi

    1981-01-01

    Rapid chemical analysis of allanite was studied by atomic absorption spectrophotometry. Powdered sample was fused with mixture of sodium carbonate anhydrous and borax (4 : 1 weight) in platinum crucible and sample solution was prepared. SiO 2 , Fe 2 O 3 , Al 2 O 3 , MnO and rare earth metals were determined by atomic absorption spectrophotometry, CaO, MgO and Ce 2 O 3 by titration, ThO 2 by colorimetry, and La 2 O 3 by flame photometry respectively. For sample solution treated with hydrofluoric acid and sulfuric acid. Na 2 O and K 2 O were determined by atomic absorption spectrophotometry, TiO 2 and P 2 O 5 by colorimetry. Chemical analyses for four samples were carried out and gave consistent results. (author)

  9. [The percutaneous absorption of diclofenac].

    Science.gov (United States)

    Riess, W; Schmid, K; Botta, L; Kobayashi, K; Moppert, J; Schneider, W; Sioufi, A; Strusberg, A; Tomasi, M

    1986-07-01

    The percutaneous absorption of diclofenac diethylammonium 1.16% (w/w) in a combination of emulsion cream and gel (Voltaren Emulgel) and of diclofenac sodium 1% (w/w) in a cream formulation (Voltaren cream) was investigated in guinea-pig, rabbit and man. The percutaneous absorption of diclofenac sodium in guinea-pig was 3 to 6% of the dose when the cream formulation in doses of 320, 100 or 40 mg was applied on 10 cm2 of occluded skin and left in place for 6 h. The transdermal delivery of 14C-labelled diclofenac yielded plateau plasma concentrations of radiotracer from 1.5 h after application until removal of the residual cream. Subsequently the steady state drug depots in the skin and muscle tissue were depleted promptly. During daily administration the steady state levels in the muscle tissue in proximity to the application site were about 3 times higher than in distant muscle tissue. By topical application on knee joints of rabbits diclofenac penetrated into the patellar ligament, the adipose corpus and the synovial fluid. In man the percutaneous absorption was 6% of the dose when the Emulgel formulation was spread by 5 mg/cm2 and left for 12 h on non-occluded skin. The pattern of metabolites of diclofenac in human urine was the same after topical and oral administration. In man, upon daily topical administration of 3 times 2.5 g cream formulation (10 mg/cm2) the diclofenac steady state plasma levels were 20 to 40 nmol/l.(ABSTRACT TRUNCATED AT 250 WORDS)

  10. Nasal Absorption of Macromolecules from Powder Formulations and Effects of Sodium Carboxymethyl Cellulose on Their Absorption.

    Directory of Open Access Journals (Sweden)

    Akiko Tanaka

    Full Text Available The nasal absorption of macromolecules from powder formulations and the effect of sodium carboxymethyl cellulose (CMC-Na as a pharmaceutical excipient on their absorption were studied. Model macromolecules were fluorescein isothiocyanate-labeled dextran (average molecular weight of 4.4kDa, FD4 and insulin. The plasma concentration of FD4 after application of the powder containing 50% starch (control was higher than that after application of the solution, and the absorption from 50% starch powder was enhanced by the substitution of starch with CMC-Na. The fractional absorption of FD4 after administration of the CMC-Na powder formulation was 30% and 40% higher than that after administration from the solution and the starch powder, respectively. The nasal absorption of insulin from the powder and the effect of CMC-Na were similar with those of FD4. The effective absorption of FD4 and insulin after application of powder with CMC-Na could be due to the increase in the nasal residence of FD4 and insulin. No damage in the nasal mucosa or dysfunction of the mucociliary clearance was observed after application of the drug powder and CMC-Na. The present findings indicate that nasal delivery of powder formulations with the addition of CMC-Na as an excipient is a promising approach for improving the nasal absorption of macromolecules.

  11. Percutaneous absorption and disposition of Tinopal EMS

    International Nuclear Information System (INIS)

    Black, T.G.; Moule, R.C.; Philp, J.

    1977-01-01

    A cotton-substantive, anionic, fluorescent whitening agent manufactured by several suppliers under various trade names e.g. Tinopal EMS, has been synthesized in radioactive form. Intubation of detergent or aqueous solution into rats resulted in little absorption from the intestinal tract as evidenced by low radioactivity in the urine and tissues. Most of the dose was excreted rapidly in the faeces. After parenteral administration to rats, the radioactivity was rapidly excreted in the faeces with small amounts remaining in tissues and organs. There was slight evidence of retention of radioactivity in the kidneys. Very small amounts of Tinopal EMS in detergent were absorbed through rat skin, but only when concentrations greater than those normally used by the consumer, together with occlusion of the skin were employed. Small amounts were absorbed through skin when applied in ethanol. It is concluded that the possibility of systemic toxic effects in man as a result of percutaneous absorption is remote

  12. Self-emulsifying drug delivery systems (SEDDS): formulation development, characterization, and applications.

    Science.gov (United States)

    Singh, Bhupinder; Bandopadhyay, Shantanu; Kapil, Rishi; Singh, Ramandeep; Katare, O

    2009-01-01

    Self-emulsifying drug delivery systems (SEDDS) possess unparalleled potential in improving oral bioavailability of poorly water-soluble drugs. Following their oral administration, these systems rapidly disperse in gastrointestinal fluids, yielding micro- or nanoemulsions containing the solubilized drug. Owing to its miniscule globule size, the micro/nanoemulsifed drug can easily be absorbed through lymphatic pathways, bypassing the hepatic first-pass effect. We present an exhaustive and updated account of numerous literature reports and patents on diverse types of self-emulsifying drug formulations, with emphasis on their formulation, characterization, and systematic optimization strategies. Recent advancements in various methodologies employed to characterize their globule size and shape, ability to encapsulate the drug, gastrointestinal and thermodynamic stability, rheological characteristics, and so forth, are discussed comprehensively to guide the formula-tor in preparing an effective and robust SEDDS formulation. Also, this exhaustive review offers an explicit discussion on vital applications of the SEDDS in bioavailability enhancement of various drugs, outlining an overview on myriad in vitro, in situ, and ex vivo techniques to assess the absorption and/ or permeation potential of drugs incorporated in the SEDDS in animal and cell line models, and the subsequent absorption pathways followed by them. In short, the current article furnishes an updated compilation of wide-ranging information on all the requisite vistas of the self-emulsifying formulations, thus paving the way for accelerated progress into the SEDDS application in pharmaceutical research.

  13. Perceived efficacy of analgesic drug regimens used for koalas (Phascolarctos cinereus) in Australia.

    Science.gov (United States)

    de Kauwe, Tyron; Kimble, Benjamin; Govendir, Merran

    2014-06-01

    Recent publications report that some therapeutic drugs used in koalas (Phascolarctos cinereus) have poor oral absorption and are rapidly eliminated. Therefore, information on both the analgesic drug dosage regimens used to treat koalas in Australia and koala caretakers' perceptions of the efficacy of these drugs to control pain was collected for the purpose of identifying the most popular analgesics to prioritize future analgesic pharmacokinetic studies for this species. A one-page, double-sided questionnaire was distributed both electronically and by mail to Australian koala care facilities such as zoos and wildlife hospitals. Information was received from 13 respondents. Nonsteroidal anti-inflammatory drugs (NSAIDs) were the most frequently used analgesics, followed by full micro- and partial opioid receptor agonists and acetaminophen with or without codeine. The full micro-opioid receptor agonists and acetaminophen with or without codeine were most consistently considered efficacious, with wider variation in perceived efficacy of the NSAIDs. Analgesic drug combinations were generally thought efficacious.

  14. Vitamin A absorption

    International Nuclear Information System (INIS)

    Baker, S.J.

    1976-01-01

    Investigation of the absorption of vitamin A and related substances is complicated by the multiplicity of forms in which they occur in the diet and by the possibility that they may be subject to different mechanisms of absorption. Present knowledge of these mechanisms is inadequate, especially in the case of carotenoids. Numerous tests of absorption have been developed. The most common has been the biochemical measurement of the rise in plasma vitamin A after an oral dose of retinol or retinyl ester, but standardization is inadequate. Radioisotope tests based upon assay of serum or faecal activity following oral administration of tritiated vitamin A derivaties hold considerable promise, but again standardization is inadequate. From investigations hitherto performed it is known that absorption of vitamin A is influenced by several diseases, although as yet the consistency of results and the correlation with other tests of intestinal function have often been poor. However, the test of vitamin A absorption is nevertheless of clinical importance as a specialized measure of intestinal function. (author)

  15. 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 ...

  16. 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...

  17. Drug detection by terahertz time-domain spectroscopy

    International Nuclear Information System (INIS)

    Duan Ruixin; Zhu Yiming; Zhao Hongwei

    2013-01-01

    Due to unique spectral region, functional imaging ability, excellent penetration and safety characteristics of terahertz radiation, the terahertz technology rapidly becomes a vital method to detect and analyze drugs. In this paper, firstly, we identify the functional groups of anti-diabetic drugs by density functional theory (DFT), HIPHOP models and experimental results from terahertz time-domain spectroscopy measurements. Secondly, we identify four kinds of herbs of radix curcumae by using the support vector machine (SVM) analysis. Besides, we analyze the absorption of anhydrous and hydrous glucose, and determine the state of water in the crystalized D-glucose·H 2 O through the results of differential scanning calorimetry measurement. Finally, we summarize the advantages and disadvantages of terahertz time-domain spectroscopy method in drug detection and analyzing. (authors)

  18. 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.

  19. 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.

  20. 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 ...

  1. [Drugs in pregnancy].

    Science.gov (United States)

    Danchev, N; Astrug, A; Tsankova, V; Nikolova, I

    2006-01-01

    The use of drugs in pregnancy is being discussed. The influence of different factors, both physiological and drug related (physicochemical characteristics, dose, duration of pharmacotherapy) on the processes of absorption, distribution, protein binding, metabolism and excretion are reviewed. The up-to-date classification of the drugs in relation to their effects on the fetus is presented. Special emphasize is given to drugs (antibiotics, cardio-vascular, psychotropic etc.) used for the treatment of acute and chronic conditions in the course of pregnancy. Drugs used for symptoms like pain, high temperature and constipation are also reviewed. Recommendations for the use of safer drugs in pregnancy are given. Drugs with proven teratogenic effects are presented.

  2. Absorption of ultraviolet radiation by antarctic phytoplankton

    Energy Technology Data Exchange (ETDEWEB)

    Vernet, M.; Mitchell, B.G. (Univ. of California-San Diego, La Jolla (United States))

    1990-01-09

    Antarctic phytoplankton contain UV-absorbing compounds that may block damaging radiation. Compounds that absorb from 320-340 nm were observed in spectral absorption of both particulates and in methanol extracts of the particulates. The decrease in the total concentration of these UV compounds with respect to chlorophyll a, as measured by the ratio of in vitro absorption at 335 nm to absorption at 665 nm is variable and decreases with depth. We observed up to 5-fold decrease in this ratio for samples within the physically mixes surface layer. The absorption of UV radiation in methanol extracts, which peaks from 320 to 340 nm, may be composed of several compounds. Shifts in peak absorption with depth (for example, from 331 nm at surface to 321 nm at 75 m), may be interpreted as a change in composition. Ratios of protective yellow xanthophylls (diadinoxanthin + diatoxanthin) to photosynthetic fucoxanthin-like pigments have highest values in surface waters. As these pigments also absorb in the near UV, their function might extend to protection as well as utilization of UV radiation for photosynthesis. We document strong absorption in the UV from 320-330 nm for Antarctic marine particulates. Below this region of the solar energy spectrum, absolute energy levels of incident radiation drop off dramatically. Only wavelengths shorter than about 320 nm will be significantly enhanced due to ozone depletion. If the absorption we observed serves a protective role for phytoplankton photosynthesis, it appears the peak band is in the region where solar energy increases rapidly, and not in the region where depletion would cause significant variations in absolute flux.

  3. Physiologically Based Pharmacokinetic and Absorption Modeling for Osmotic Pump Products.

    Science.gov (United States)

    Ni, Zhanglin; Talattof, Arjang; Fan, Jianghong; Tsakalozou, Eleftheria; Sharan, Satish; Sun, Dajun; Wen, Hong; Zhao, Liang; Zhang, Xinyuan

    2017-07-01

    Physiologically based pharmacokinetic (PBPK) and absorption modeling approaches were employed for oral extended-release (ER) drug products based on an osmotic drug delivery system (osmotic pumps). The purpose was to systemically evaluate the in vivo relevance of in vitro dissolution for this type of formulation. As expected, in vitro dissolution appeared to be generally predictive of in vivo PK profiles, because of the unique feature of this delivery system that the in vitro and in vivo release of osmotic pump drug products is less susceptible to surrounding environment in the gastrointestinal (GI) tract such as pH, hydrodynamic, and food effects. The present study considered BCS (Biopharmaceutics Classification System) class 1, 2, and 3 drug products with half-lives ranging from 2 to greater than 24 h. In some cases, the colonic absorption models needed to be adjusted to account for absorption in the colon. C max (maximum plasma concentration) and AUCt (area under the concentration curve) of the studied drug products were sensitive to changes in colon permeability and segmental GI transit times in a drug product-dependent manner. While improvement of the methodology is still warranted for more precise prediction (e.g., colonic absorption and dynamic movement in the GI tract), the results from the present study further emphasized the advantage of using PBPK modeling in addressing product-specific questions arising from regulatory review and drug development.

  4. Neutron resonance absorption theory

    International Nuclear Information System (INIS)

    Reuss, P.

    1991-11-01

    After some recalls on the physics of neutron resonance absorption during their slowing down, this paper presents the main features of the theoretical developments performed by the french school of reactor physics: the effective reaction rate method so called Livolant-Jeanpierre theory, the generalizations carried out by the author, and the probability table method [fr

  5. Noble gas absorption process

    International Nuclear Information System (INIS)

    Thomas, J.W.

    1975-01-01

    A method of removing a noble gas from air comprising the use of activated carbon filters in stages in which absorption and desorption steps in succession are conducted in order to increase the capacity of the filters is described. (U.S.)

  6. Total photon absorption

    International Nuclear Information System (INIS)

    Carlos, P.

    1985-01-01

    Experimental methods using real photon beams for measurements of total photonuclear absorption cross section σ(Tot : E/sub γ/) are recalled. Most recent σ(Tot : E/sub γ/)results for complex nuclei and in the nucleon resonance region are presented

  7. 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...

  8. 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

  9. Hydrogel nanoparticles and nanocomposites for nasal drug/vaccine delivery.

    Science.gov (United States)

    Salatin, Sara; Barar, Jaleh; Barzegar-Jalali, Mohammad; Adibkia, Khosro; Milani, Mitra Alami; Jelvehgari, Mitra

    2016-09-01

    Over the past few years, nasal drug delivery has attracted more and more attentions, and been recognized as the most promising alternative route for the systemic medication of drugs limited to intravenous administration. Many experiments in animal models have shown that nanoscale carriers have the ability to enhance the nasal delivery of peptide/protein drugs and vaccines compared to the conventional drug solution formulations. However, the rapid mucociliary clearance of the drug-loaded nanoparticles can cause a reduction in bioavailability percentage after intranasal administration. Thus, research efforts have considerably been directed towards the development of hydrogel nanosystems which have mucoadhesive properties in order to maximize the residence time, and hence increase the period of contact with the nasal mucosa and enhance the drug absorption. It is most certain that the high viscosity of hydrogel-based nanosystems can efficiently offer this mucoadhesive property. This update review discusses the possible benefits of using hydrogel polymer-based nanoparticles and hydrogel nanocomposites for drug/vaccine delivery through the intranasal administration.

  10. [Drug-Drug Interactions with Consideration of Pharmacogenetics].

    Science.gov (United States)

    Ozawa, Shogo

    2018-01-01

     Elderly patients often suffer from a variety of diseases and therefore may be prescribed several kinds of drugs. Interactions between these drugs may cause problems in some patients. Guidelines for drug interactions were released on July 8, 2014 "Drug Interaction Guideline for Drug Development and Labeling Recommendations (Final Draft)". These guidelines include the theoretical basis for evaluating the mechanisms of drug interaction, the possible extent of drug interactions, and take into consideration special populations (e.g., infants, children, elderly patients, patients with hepatic or renal dysfunction, and subjects with minor deficient alleles for drug metabolizing enzymes and drug transporters). In this symposium article, I discuss this last special population: altered drug metabolism and drug interactions in subjects with minor alleles of genes encoding deficient drug metabolizing enzymes. I further discuss a drug label for eliglustat (Cerdelga) with instructions for patients with ultra-rapid, extensive, intermediate, and poor metabolizer phenotypes that arise from different CYP2D6 gene alleles.

  11. Projecting future drug expenditures--2009.

    Science.gov (United States)

    Hoffman, James M; Shah, Nilay D; Vermeulen, Lee C; Doloresco, Fred; Martin, Patrick K; Blake, Sharon; Matusiak, Linda; Hunkler, Robert J; Schumock, Glen T

    2009-02-01

    Drug expenditure trends in 2007 and 2008, projected drug expenditures for 2009, and factors likely to influence drug expenditures are discussed. Various factors are likely to influence drug expenditures in 2009, including drugs in development, the diffusion of new drugs, drug safety concerns, generic drugs, Medicare Part D, and changes in the drug supply chain. The increasing availability of important generic drugs and drug safety concerns continue to moderate growth in drug expenditures. The drug supply chain remains dynamic and may influence drug expenditures, particularly in specialized therapeutic areas. Initial data suggest that the Medicare Part D benefit has influenced drug expenditures, but the ultimate impact of the benefit on drug expenditures remains unclear. From 2006 to 2007, total U.S. drug expenditures increased by 4.0%, with total spending rising from $276 billion to $287 billion. Drug expenditures in clinics continue to grow more rapidly than in other settings, with a 9.9% increase from 2006 to 2007. Hospital drug expenditures increased at a moderate rate of only 1.6% from 2006 to 2007; through the first nine months of 2008, hospital drug expenditures increased by only 2.8% compared with the same period in 2007. In 2009, we project a 0-2% increase in drug expenditures in outpatient settings, a 1-3% increase in expenditures for clinic-administered drugs, and a 1-3% increase in hospital drug expenditures.

  12. 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.

  13. Drug Facts

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    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 ...

  14. Drug Facts

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    Full Text Available ... Facts Search form Search Menu Home Drugs That People Abuse Alcohol Facts Bath Salts Facts Cocaine (Coke, ... Drugs? Effects of Drugs Drug Use and Other People Drug Use and Families Drug Use and Kids ...

  15. Drug Facts

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    Full Text Available ... People Drug Use and Families Drug Use and Kids Drug Use and Unborn Children Drug Use and ... Children and Teens Stay Drug-Free Talking to Kids About Drugs: What to Say if You Used ...

  16. Supersaturating drug delivery systems

    DEFF Research Database (Denmark)

    Laitinen, Riikka; Löbmann, Korbinian; Grohganz, Holger

    2017-01-01

    of the bioavailability of poorly water-soluble drugs by increasing the driving force for drug absorption. However, ASDs often require a high weight percentage of carrier (usually a hydrophilic polymer) to ensure molecular mixing of the drug in the carrier and stabilization of the supersaturated state, often leading......Amorphous solid dispersions (ASDs) are probably the most common and important supersaturating drug delivery systems for the formulation of poorly water-soluble compounds. These delivery systems are able to achieve and maintain a sustained drug supersaturation which enables improvement...... strategy for poorly-soluble drugs. While the current research on co-amorphous formulations is focused on preparation and characterization of these systems, more detailed research on their supersaturation and precipitation behavior and the effect of co-formers on nucleation and crystal growth inhibition...

  17. Mechanisms for oral absorption of poorly water-soluble compounds

    DEFF Research Database (Denmark)

    Lind, Marianne Ladegaard

    Abstract A large part of the new drug candidates discovered by the pharmaceutical industry have poor solubility in aqueous media. The preferred route of drug administration is the oral route, but for these poorly water-soluble drug candidates the oral bioavailability can be low and variable. Often......, phospholipids) and exogenous surfactants used in pharmaceutical formulations on the oral absorption of poorly water-soluble drug substances. Three different models were used for this purpose. The first model was the in vitro Caco-2 cell model. Simulated intestinal fluids which did not decrease cellular...... products are important for the solubilization of poorly water-soluble drug substances and thus absorption. The second model used was the lipoprotein secreting Caco-2 cell model, which was used to simulate intestinal lymphatic transport in vitro. Various simulated intestinal fluids were composed...

  18. Linear absorptive dielectrics

    Science.gov (United States)

    Tip, A.

    1998-06-01

    Starting from Maxwell's equations for a linear, nonconducting, absorptive, and dispersive medium, characterized by the constitutive equations D(x,t)=ɛ1(x)E(x,t)+∫t-∞dsχ(x,t-s)E(x,s) and H(x,t)=B(x,t), a unitary time evolution and canonical formalism is obtained. Given the complex, coordinate, and frequency-dependent, electric permeability ɛ(x,ω), no further assumptions are made. The procedure leads to a proper definition of band gaps in the periodic case and a new continuity equation for energy flow. An S-matrix formalism for scattering from lossy objects is presented in full detail. A quantized version of the formalism is derived and applied to the generation of Čerenkov and transition radiation as well as atomic decay. The last case suggests a useful generalization of the density of states to the absorptive situation.

  19. Gamma absorption meter

    International Nuclear Information System (INIS)

    Dincklage, R.D. von.

    1984-01-01

    The absorption meter consists of a radiation source, a trough for the absorbing liquid and a detector. It is characterized by the fact that there is a foil between the detector and the trough, made of a material whose binding energy of the K electrons is a little greater than the energy of the photons emitted by the radiation source. The source of radiation and foil are replaceable. (orig./HP) [de

  20. Total Absorption Spectroscopy

    International Nuclear Information System (INIS)

    Rubio, B.; Gelletly, W.

    2007-01-01

    The problem of determining the distribution of beta decay strength (B(GT)) as a function of excitation energy in the daughter nucleus is discussed. Total Absorption Spectroscopy is shown to provide a way of determining the B(GT) precisely. A brief history of such measurements and a discussion of the advantages and disadvantages of this technique, is followed by examples of two recent studies using the technique. (authors)

  1. Drug metabolism and ageing.

    Science.gov (United States)

    Wynne, Hilary

    2005-06-01

    Older people are major consumers of drugs and because of this, as well as co-morbidity and age-related changes in pharmacokinetics and pharmacodynamics, are at risk of associated adverse drug reactions. While age does not alter drug absorption in a clinically significant way, and age-related changes in volume of drug distribution and protein binding are not of concern in chronic therapy, reduction in hepatic drug clearance is clinically important. Liver blood flow falls by about 35% between young adulthood and old age, and liver size by about 24-35% over the same period. First-pass metabolism of oral drugs avidly cleared by the liver and clearance of capacity-limited hepatically metabolized drugs fall in parallel with the fall in liver size, and clearance of drugs with a high hepatic extraction ratio falls in parallel with the fall in hepatic blood flow. In normal ageing, in general, activity of the cytochrome P450 enzymes is preserved, although a decline in frail older people has been noted, as well as in association with liver disease, cancer, trauma, sepsis, critical illness and renal failure. As the contribution of age, co-morbidity and concurrent drug therapy to altered drug clearance is impossible to predict in an individual older patient, it is wise to start any drug at a low dose and increase this slowly, monitoring carefully for beneficial and adverse effects.

  2. Self-microemulsifying drug delivery system for improved oral bioavailability of dipyridamole: preparation and evaluation.

    Science.gov (United States)

    Guo, Feng; Zhong, Haijun; He, Jing; Xie, Baogang; Liu, Fen; Xu, Helin; Liu, Minmin; Xu, Chunlian

    2011-07-01

    Dipyridamole shows poor and variable bioavailability after oral administration due to pHdependent solubility, low biomembrane permeability as well as being a substrate of P-glycoprotein. In order to improve the oral absorption of dipyridamole, a self-microemulsifying drug delivery system (SMEDDS) for dipyridamole was prepared and evaluated in vitro and in vivo. The optimum formulation was 18% oleic acid, 12% Labrafac lipophile WL 1349, 42% Solutol HS 15 and 28% isopropyl alcohol. It was found that the performance of self-microemulsification with the combination of oleic acid and Labrafac lipophile WL 1349 increased compared with just one oil. The results obtained from an in vitro dissolution assay indicated that dipyridamole in SMEDDS dissolved rapidly and completely in pH 6.8 aqueous media, while the commercial drug tablet was less soluble. An oral bioavailability study in rats showed that dipyridamole in the SMEDDS formulation had a 2.06-fold increased absorption compared with the simple drug suspension. It was evident that SMEDDS may be an effective approach to improve the oral absorption for drugs having pH-dependent solubility.

  3. 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...

  4. 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.

  5. Drugs and the Brain: An Introduction to Neuropharmacology. Pamphlet Series.

    Science.gov (United States)

    Brick, John

    The thousands of different drugs on the market can be separated into two categories: drugs that affect behavior, called psychoactive drugs, and drugs that do not affect behavior. Drugs get into the body by mouth, inhalation into the lungs, by injection into a vein, muscle or under the skin, and by absorption through mucous membranes. Regardless of…

  6. Optical absorption in dendrimers

    International Nuclear Information System (INIS)

    Supritz, C.; Engelmann, A.; Reineker, P.

    2004-01-01

    Dendrimers are highly branched molecules, which are expected to be useful, for example, as efficient artificial light harvesting systems in nano-technological applications. There are two different classes of dendrimers: compact dendrimers with constant distance between neighboring branching points throughout the macromolecule and extended dendrimers, where this distance increases from the system periphery to the center. We investigate the linear absorption spectra of these dendrimer types using the Frenkel exciton concept. The electron-phonon interaction is taken into account by introducing a heat bath that interacts with the exciton in a stochastic manner

  7. 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...

  8. 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.

  9. Drug Facts

    Medline Plus

    Full Text Available ... Treatment and Recovery Resources? Prevention Help Children and Teens Stay Drug-Free Talking to Kids About Drugs: What to Say if You Used Drugs in the Past Drug Use ... Videos Information About Drugs Alcohol ...

  10. 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, ...

  11. 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.

  12. Nanostructured lipid carriers versus microemulsions for delivery of the poorly water-soluble drug luteolin.

    Science.gov (United States)

    Liu, Ying; Wang, Lan; Zhao, Yiqing; He, Man; Zhang, Xin; Niu, Mengmeng; Feng, Nianping

    2014-12-10

    Nanostructured lipid carriers and microemulsions effectively deliver poorly water-soluble drugs. However, few studies have investigated their ability and difference in improving drug bioavailability, especially the factors contributed to the difference. Thus, this study was aimed at investigating their efficiency in bioavailability enhancement based on studying two key processes that occur in NLC and ME during traverse along the intestinal tract: the solubilization process and the intestinal permeability process. The nanostructured lipid carriers and microemulsions had the same composition except that the former were prepared with solid lipids and the latter with liquid lipids; both were evaluated for particle size and zeta potential. Transmission electron microscopy, differential scanning calorimetry, and X-ray diffraction were performed to characterize their properties. Furthermore, in vitro drug release, in situ intestinal absorption, and in vitro lipolysis were studied. The bioavailability of luteolin delivered using nanostructured lipid carriers in rats was compared with that delivered using microemulsions and suspensions. The in vitro analysis revealed different release mechanisms for luteolin in nanostructured lipid carriers and microemulsions, although the in situ intestinal absorption was similar. The in vitro lipolysis data indicated that digestion speed and extent were higher for microemulsions than for nanostructured lipid carriers, and that more of the former partitioned to the aqueous phase. The in vivo bioavailability analysis in rats indicated that the oral absorption and bioavailability of luteolin delivered using nanostructured lipid carriers and microemulsions were higher than those of luteolin suspensions. Nanostructured lipid carriers and microemulsions improved luteolin's oral bioavailability in rats. The rapid lipid digestion and much more drug solubilized available for absorption in microemulsions may contribute to better absorption and

  13. Evaluation of the Percutaneous Absorption of Ketamine HCl, Gabapentin, Clonidine HCl, and Baclofen, in Compounded Transdermal Pain Formulations, Using the Franz Finite Dose Model.

    Science.gov (United States)

    Bassani, August S; Banov, Daniel

    2016-02-01

    This study evaluates the ability of four commonly used analgesics (ketamine HCl, gabapentin, clonidine HCl, and baclofen), when incorporated into two transdermal compounding bases, Lipoderm and Lipoderm ActiveMax, to penetrate human cadaver trunk skin in vitro, using the Franz finite dose model. In vitro experimental study. Methods. Ketamine HCl 5% w/w, gabapentin 10% w/w, clonidine HCl 0.2% w/w, and baclofen 2% w/w were compounded into two transdermal bases, Lipoderm and Lipoderm ActiveMax. Each compounded drug formulation was tested on skin from three different donors and three replicate skin sections per donor. The Franz finite dose model was used in this study to evaluate the percutaneous absorption and distribution of drugs within each formulation. Rapid penetration to peak flux was detected for gabapentin and baclofen at approximately 1 hour after application. Clonidine HCl also had a rapid penetration to peak flux occurring approximately 1 hour after application and had a secondary peak at approximately 40 hours. Ketamine HCl exhibited higher overall absorption rates than the other drugs, and peaked at 6–10 hours. Similar patterns of drug distribution within the skin were also observed using both transdermal bases. This study suggests that the combination of these 4 analgesic drugs can be successfully delivered transdermally, using either Lipoderm or Lipoderm ActiveMax. Compounded transdermal drug preparations may then provide physicians with an alternative to traditional oral pain management regimens that can be personalized to the specific patient with the potential for enhanced pain control.

  14. The absorption of plutonium by anion resins

    Energy Technology Data Exchange (ETDEWEB)

    Durham, R. W.; Mills, R.

    1961-10-15

    Equilibrium experiments have shown Pu{sup +4} to be absorbed from nitric acid onto an anion resin as a complex anion Pu(NO{sub 3}){sub 6}{sup -2}. The amount of absorption is dependent on the plutonium and nitric acid concentrations in the equilibrium solution with a maximum at 7N to 8N HNO{sub 3}. A low cross-linked resin has a higher capacity and reaches equilibrium more rapidly than the normally supplied resin. Saturation capacity of one per cent cross-linked Nalcite SBR (Dowex 1), 50 -- 100 mesh, is 385 mg Pu/gram dry resin. (author)

  15. Drug-mineral interactions

    International Nuclear Information System (INIS)

    Kramer, L.

    1986-01-01

    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

  16. Atomic absorption spectrometry

    International Nuclear Information System (INIS)

    Haswell, S.J.

    1991-01-01

    Atomic absorption spectroscopy is now well established and widely used technique for the determination of trace and major elements in a wide range analyte types. There have been many advances in the atomic spectroscopy over the last decade and for this reason and to meet the demand, it was felt that there was a need for an updated book. Whilst interest in instrumental design has tended to dominate the minds of the spectrocopist, the analyst concerned with obtaining reliable and representative data, in diverse areas of application, has been diligently modifying and developing sample treatment and instrumental introduction techniques. Such methodology is de fundamental part of analysis and form the basis of the fourteen application chapters of this book. The text focuses in the main on AAS; however, the sample handling techniques described are in many cases equally applicable to ICP-OES and ICP-MS analysis. (author). refs.; figs.; tabs

  17. Atomic absorption spectrophotometer

    International Nuclear Information System (INIS)

    Stockdale, T. J.

    1985-01-01

    In atomic absorption spectrophotometer, a reference path may be provided for radiation which excludes the flame. This radiation provides a signal from a detector which varies only with the instrumental drift produced by variations in the radiation source brightness and by variations in detector gain. The signal can be used to compensate for drift in other signals received through a sample path including the flame. In the present invention, radiation passes through the sample path continuously during measurement, and only through the reference path between sample measurements. Movable mirrors shift the radiation between the paths upon externally applied commands. Conveniently, the reference path measurement is made while the flame is stabilized during the change between samples. The reference path measurements are stored and used to correct for drift

  18. Analyzing Water's Optical Absorption

    Science.gov (United States)

    2002-01-01

    A cooperative agreement between World Precision Instruments (WPI), Inc., and Stennis Space Center has led the UltraPath(TM) device, which provides a more efficient method for analyzing the optical absorption of water samples at sea. UltraPath is a unique, high-performance absorbance spectrophotometer with user-selectable light path lengths. It is an ideal tool for any study requiring precise and highly sensitive spectroscopic determination of analytes, either in the laboratory or the field. As a low-cost, rugged, and portable system capable of high- sensitivity measurements in widely divergent waters, UltraPath will help scientists examine the role that coastal ocean environments play in the global carbon cycle. UltraPath(TM) is a trademark of World Precision Instruments, Inc. LWCC(TM) is a trademark of World Precision Instruments, Inc.

  19. Increasing oral absorption of polar neuraminidase inhibitors: a prodrug transporter approach applied to oseltamivir analogue.

    Science.gov (United States)

    Gupta, Deepak; Varghese Gupta, Sheeba; Dahan, Arik; Tsume, Yasuhiro; Hilfinger, John; Lee, Kyung-Dall; Amidon, Gordon L

    2013-02-04

    Poor oral absorption is one of the limiting factors in utilizing the full potential of polar antiviral agents. The neuraminidase target site requires a polar chemical structure for high affinity binding, thus limiting oral efficacy of many high affinity ligands. The aim of this study was to overcome this poor oral absorption barrier, utilizing prodrug to target the apical brush border peptide transporter 1 (PEPT1). Guanidine oseltamivir carboxylate (GOCarb) is a highly active polar antiviral agent with insufficient oral bioavailability (4%) to be an effective therapeutic agent. In this report we utilize a carrier-mediated targeted prodrug approach to improve the oral absorption of GOCarb. Acyloxy(alkyl) ester based amino acid linked prodrugs were synthesized and evaluated as potential substrates of mucosal transporters, e.g., PEPT1. Prodrugs were also evaluated for their chemical and enzymatic stability. PEPT1 transport studies included [(3)H]Gly-Sar uptake inhibition in Caco-2 cells and cellular uptake experiments using HeLa cells overexpressing PEPT1. The intestinal membrane permeabilities of the selected prodrugs and the parent drug were then evaluated for epithelial cell transport across Caco-2 monolayers, and in the in situ rat intestinal jejunal perfusion model. Prodrugs exhibited a pH dependent stability with higher stability at acidic pHs. Significant inhibition of uptake (IC(50) 30-fold increase in affinity compared to GOCarb. The l-valyl prodrug exhibited significant enhancement of uptake in PEPT1/HeLa cells and compared favorably with the well-absorbed valacyclovir. Transepithelial permeability across Caco-2 monolayers showed that these amino acid prodrugs have a 2-5-fold increase in permeability as compared to the parent drug and showed that the l-valyl prodrug (P(app) = 1.7 × 10(-6) cm/s) has the potential to be rapidly transported across the epithelial cell apical membrane. Significantly, only the parent drug (GOCarb) appeared in the basolateral

  20. Atomic absorption spectrophotometry in perspective

    International Nuclear Information System (INIS)

    Soffiantini, V.

    1981-01-01

    Atomic absorption spectrophotometry is essentially an analytical technique used for quantitative trace metal analysis in a variety of materials. The speed and specificity of the technique is its greatest advantage over other analytical techniques. What atomic absorption spectrophotometry can and cannot do and its advantages and disadvantages are discussed, a summary of operating instructions are given, as well as a summary of analytical interferences. The applications of atomic absorption spectrophotometry are also shortly discussed

  1. Nonlinear effects in collective absorption

    International Nuclear Information System (INIS)

    Uenoyama, Takeshi; Mima, Kunioki; Watanabe, Tsuguhiro.

    1981-01-01

    The collective absorption of high intensity laser radiation is analyzed numerically. Density profile modification due to the ponderomotive force associating laser radiation and the excited electron plasma waves is self-consistently taken into account, and the intensity dependences of the absorption efficiency are obtained. In the high intensity regime, the absorption efficiency is found to be strongly enhanced in the plasma without flow, but reduced with supersonic flow. (author)

  2. Harnessing Multiple Internal Reflections to Design Highly Absorptive Acoustic Metasurfaces

    Science.gov (United States)

    Shen, Chen; Cummer, Steven A.

    2018-05-01

    The rapid development of metasurfaces has enabled numerous intriguing applications with acoustically thin sheets. Here we report the theory and experimental realization of a nonresonant sound-absorbing strategy using metasurfaces by harnessing multiple internal reflections. We theoretically and numerically show that the higher-order diffraction of thin gradient-index metasurfaces is tied to multiple internal reflections inside the unit cells. Highly absorbing acoustic metasurfaces can be realized by enforcing multiple internal reflections together with a small amount of loss. A reflective gradient-index acoustic metasurface is designed based on the theory, and we further experimentally verify the performance using a three-dimensional printed prototype. Measurements show over 99% energy absorption at the peak frequency and a 95% energy absorption bandwidth of around 600 Hz. The proposed mechanism provides an alternative route for sound absorption without the necessity of high absorption of the individual unit cells.

  3. Sex Differences in Drug Abuse

    OpenAIRE

    Becker, Jill B.; Hu, Ming

    2007-01-01

    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 abstin...

  4. Atomic absorption analysis of serial titanium alloys

    International Nuclear Information System (INIS)

    Gorlova, M.N.; Feofanova, N.M.; Kornyushkova, Yu.D.

    1977-01-01

    Atom-absorption technique is described, which makes it possible to rapidly and precisely determine the following alloying elements and admixtures in titanium alloys: Al (2.0 - 8.5%); Mo (0.5 - 8%); Cr (0.5 - 12%); Si (0.2 - 0.5%); Mn(0.2 - 2.5%); V(0.5 - 6%); Sn(2.0 - 3.0%); Fe(0.1 - 1.0%); Zr(2.0 - 12.0%). The atom absorption method with flame atomization of the sample provides for best results if the alloy is dissolved in a mixture HCl + HBF 4 in the ratio 2:1. In order to obtain correct results the standard solutions must contain titanium in concentrations corresponding to the weight of the sample being analyzed. Sensitivity of zirconium determination may be increased approximately twofold by adding 10 mg/ml of FeCl 3 into the solution. Being as precise, as the classic analytical methods, the atom absorption technique is about 5 times more efficient

  5. 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.

  6. Glucose Absorption by the Bacillary Band of Trichuris muris.

    Directory of Open Access Journals (Sweden)

    Tina V A Hansen

    2016-09-01

    Full Text Available A common characteristic of Trichuris spp. infections in humans and animals is the variable but low efficacy of single-dose benzimidazoles currently used in mass drug administration programmes against human trichuriasis. The bacillary band, a specialised morphological structure of Trichuris spp., as well as the unique partly intracellular habitat of adult Trichuris spp. may affect drug absorption and perhaps contribute to the low drug accumulation in the worm. However, the exact function of the bacillary band is still unknown.We studied the dependency of adult Trichuris muris on glucose and/or amino acids for survival in vitro and the absorptive function of the bacillary band. The viability of the worms was evaluated using a motility scale from 0 to 3, and the colorimetric assay Alamar Blue was utilised to measure the metabolic activity. The absorptive function of the bacillary band in living worms was explored using a fluorescent glucose analogue (6-NBDG and confocal microscopy. To study the absorptive function of the bacillary band in relation to 6-NBDG, the oral uptake was minimised or excluded by sealing the oral cavity with glue and agarose.Glucose had a positive effect on both the motility (p < 0.001 and metabolic activity (p < 0.001 of T. muris in vitro, whereas this was not the case for amino acids. The 6-NBDG was observed in the pores of the bacillary band and within the stichocytes of the living worms, independent of oral sealing.Trichuris muris is dependent on glucose for viability in vitro, and the bacillary band has an absorptive function in relation to 6-NBDG, which accumulates within the stichocytes. The absorptive function of the bacillary band calls for an exploration of its possible role in the uptake of anthelmintics, and as a potential anthelmintic target relevant for future drug development.

  7. [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

  8. Nanoparticle-Mediated Pulmonary Drug Delivery: A Review

    Directory of Open Access Journals (Sweden)

    Mukta Paranjpe

    2014-04-01

    Full Text Available Colloidal drug delivery systems have been extensively investigated as drug carriers for the application of different drugs via different routes of administration. Systems, such as solid lipid nanoparticles, polymeric nanoparticles and liposomes, have been investigated for a long time for the treatment of various lung diseases. The pulmonary route, owing to a noninvasive method of drug administration, for both local and systemic delivery of an active pharmaceutical ingredient (API forms an ideal environment for APIs acting on pulmonary diseases and disorders. Additionally, this route offers many advantages, such as a high surface area with rapid absorption due to high vascularization and circumvention of the first pass effect. Aerosolization or inhalation of colloidal systems is currently being extensively studied and has huge potential for targeted drug delivery in the treatment of various diseases. Furthermore, the surfactant-associated proteins present at the interface enhance the effect of these formulations by decreasing the surface tension and allowing the maximum effect. The most challenging part of developing a colloidal system for nebulization is to maintain the critical physicochemical parameters for successful inhalation. The following review focuses on the current status of different colloidal systems available for the treatment of various lung disorders along with their characterization. Additionally, different in vitro, ex vivo and in vivo cell models developed for the testing of these systems with studies involving cell culture analysis are also discussed.

  9. 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 ...

  10. Drug Abuse

    Science.gov (United States)

    ... Cocaine Heroin Inhalants Marijuana Prescription drugs, including opioids Drug abuse also plays a role in many major social problems, such as drugged driving, violence, stress, and child abuse. Drug abuse can lead to ...

  11. 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 ...

  12. 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 ...

  13. Club Drugs

    Science.gov (United States)

    ... uses. Other uses of these drugs are abuse. Club drugs are also sometimes used as "date rape" drugs, to make someone unable to say no to or fight back against sexual assault. Abusing these drugs can ...

  14. Galactic absorption line coronae

    International Nuclear Information System (INIS)

    Bregman, J.N.

    1981-01-01

    We have investigated whether gaseous coronae around galaxies rise to the absorption systems seen in quasar spectra. In our model, gas originally located in the disk is heated to the million degree range and rises to surround the galaxy; the gas remains bound to the galaxy. Optically thin radiative cooling drives a thermal instability in the hot gas which causes cool clouds (T 4 K) to condense out of the corona. These clouds, which follow ballistic trajectories back to the disk, are the absorption sites. A two-dimensional hydrodynamic code with radiative cooling was used to study the dynamics and thermodynamics of the corona as well as the position rate at which clouds form. Coupled to the code is a galaxy with two mass components, a disk (approx.10 11 M/sub sun/) and a dark halo (approx.10 12 M/sub sun/). In a model where the temperature at the base of the corona (in the disk) is 3 x 10 6 K, absorbing gas of column density NL> or approx. =10 18 cm 2 extends radially to 100 kpc (face-on orientation) and vertically to 60 Kpc (edge-on orientation). The total mass of gas required here (coronal plus cloud gas) is 1.4 x 10 10 M/sub sun/, while the minimum supernova heating rate is one supernova per 27 years. In two other models (base coronal temperatures of 0.50 x 10 6 K and 1 x 10 6 K), coronal gas rises from an extended gaseous disk (in the previous model, the gas comes from a typical gaseous disk approximately 15 kpc in extent). Here, column densities of 10 19 cm -2 out to a radius of 70 kpc (face-on orientation) are achieved with a total gas mass of 1.7 x 10 9 M/sub direct-product/ and 2.0 x 10 9 M/sub sun/ and minimum heating rates of approximately one supernova per 170 years and one supernova per 60 years

  15. 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...

  16. Rapid shallow breathing

    Science.gov (United States)

    Tachypnea; Breathing - rapid and shallow; Fast shallow breathing; Respiratory rate - rapid and shallow ... Shallow, rapid breathing has many possible medical causes, including: Asthma Blood clot in an artery in the ...

  17. 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

  18. Absorption band Q model for the earth

    International Nuclear Information System (INIS)

    Anderson, D.L.; Given, J.W.

    1982-01-01

    Body wave, surface wave, and normal mode data are used to place constraints on the frequency dependence of Q in the mantle. With a simple absorption band model it is possible to satisfy the shear sensitive data over a broad frequency range. The quality factor Q/sub s/(ω) is proportional to ω/sup α/ in the band and to ω and ω -1 at higher and lower frequencies, respectively, as appropriate for a relaxation mechanism with a spectrum of relaxation time. The parameters of the band are Q(min) = 80, α = 0.15, and width, 5 decades. The center of the band varies from 10 1 seconds in the upper mantle, to 1.6 x 10 3 seconds in the lower mantle. The shift of the band with depth is consistent with the expected effects of temperature, pressure and stress. High Q, regions of the mantle are attributed to a shift of the absorption band to longer periods. To satisfy the gravest fundamental spheroidal modes and the ScS data, the absorption band must shift back into the short-period seismic band at the base of the mantle. This may be due to a high temperature gradient or high shear stresses. A preliminary attempt is also made to specify bulk dissipation in the mantle and core. Specific features of the absorption band model are low Q in the body wave band at both the top and the base of the mantle, low Q for long-period body waves in the outer core, an inner core Q 2 that increases with period, and low Q/sub p//Q/sub s/ at short periods in the middle mantel. The short-period Q/sub s/ increases rapidly at 400 km and is relatively constant from this depth to 2400 km. The deformational Q of the earth at a period of 14 months is predicted to be 463

  19. Wave energy absorption by ducks

    OpenAIRE

    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.

  20. Wave energy absorption by ducks

    DEFF Research Database (Denmark)

    Kurniawan, Adi

    2018-01-01

    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....

  1. Atomic absorption instrument functional description

    International Nuclear Information System (INIS)

    Bystroff, R.I.; Boyle, W.G. Jr.; Barton, G.W. Jr.

    1976-01-01

    This report describes a proposed system for automating atomic absorption analysis. The system consists of two atomic absorption instruments and an automatic sampler that can be attached to either instrument. A computer program controls the sampling and gathers data. The program then uses the data to perform bookkeeping, data processing, and report writing

  2. Sublinear absorption in OCS gas

    International Nuclear Information System (INIS)

    Bogani, F.; Querzoli, R.; Ernst, K.

    1988-01-01

    Sublinear absorption in OCS gas has been experimentally studied in detail by means of an optoacustic technique and transmission measurements. The best fit of the results is obtained by a phenomenological model, that considers the process as the sum of one-and two-photon absorptions

  3. Optical absorption of irradiated carbohydrates

    International Nuclear Information System (INIS)

    Supe, A.A.; Tiliks, Yu.E.

    1994-01-01

    The optical absorption spectra of γ-irradiated carbohydrates (glucose, lactose, sucrose, maltose, and starch) and their aqueous solutions were studied. The comparison of the data obtained with the determination of the concentrations of molecular and radical products of radiolysis allows the absorption bands with maxima at 250 and 310 nm to be assigned to the radicals trapped in the irradiated carbohydrates

  4. 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

  5. Subgap absorption in conjugated polymers

    Energy Technology Data Exchange (ETDEWEB)

    Sinclair, M.; Seager, C.H. (Sandia National Labs., Albuquerque, NM (USA)); McBranch, D.; Heeger, A.J. (California Univ., Santa Barbara, CA (USA)); Baker, G.L. (Bell Communications Research, Inc., Red Bank, NJ (USA))

    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 < 10{sup {minus}5}, Photothermal Deflection Spectroscopy (PDS) is ideal for determining the absorption coefficients of thin films of transparent'' materials. We have used PDS to measure the optical absorption spectra of the conjugated polymers poly(1,4-phenylene-vinylene) (and derivitives) and polydiacetylene-4BCMU in the spectral region from 0.55 eV to 3 eV. Our spectra show that the shape of the absorption edge varies considerably from polymer to polymer, with polydiacetylene-4BCMU having the steepest absorption edge. The minimum absorption coefficients measured varied somewhat with sample age and quality, but were typically in the range 1 cm{sup {minus}1} to 10 cm{sup {minus}1}. In the region below 1 eV, overtones of C-H stretching modes were observed, indicating that further improvements in transparency in this spectral region might be achieved via deuteration of fluorination. 11 refs., 4 figs.

  6. Multifunctional hybrids for electromagnetic absorption

    International Nuclear Information System (INIS)

    Huynen, I.; Quievy, N.; Bailly, C.; Bollen, P.; Detrembleur, C.; Eggermont, S.; Molenberg, I.; Thomassin, J.M.; Urbanczyk, L.

    2011-01-01

    Highlights: → EM absorption requires low dielectric constant and ∼1 S/m electrical conductivity. → New hybrids were processed with CNT-filled polymer foam inserted in Al honeycomb. → The EM absorption in the GHz range is superior to any known material. → A closed form model is used to guide the design of the hybrid. → The architectured material is light with potential for thermal management. - Abstract: Electromagnetic (EM) interferences are ubiquitous in modern technologies and impact on the reliability of electronic devices and on living cells. Shielding by EM absorption, which is preferable over reflection in certain instances, requires combining a low dielectric constant with high electrical conductivity, which are antagonist properties in the world of materials. A novel class of hybrid materials for EM absorption in the gigahertz range has been developed based on a hierarchical architecture involving a metallic honeycomb filled with a carbon nanotube-reinforced polymer foam. The waveguide characteristics of the honeycomb combined with the performance of the foam lead to unexpectedly large EM power absorption over a wide frequency range, superior to any known material. The peak absorption frequency can be tuned by varying the shape of the honeycomb unit cell. A closed form model of the EM reflection and absorption provides a tool for the optimization of the hybrid. This designed material sets the stage for a new class of sandwich panels combining high EM absorption with mass efficiency, stiffness and thermal management.

  7. Absorption and subjective effects of caffeine from coffee, cola and capsules.

    Science.gov (United States)

    Liguori, A; Hughes, J R; Grass, J A

    1997-11-01

    Coffee is often perceived as producing greater pharmacological effects than cola. The present study compared the magnitude and rapidity of peak caffeine levels and subjective effects between coffee and cola. Thirteen users of both coffee and cola (mean daily caffeine consumption = 456 mg) ingested 400 mg caffeine via 12 oz unsweetened coffee, 24 oz sugar-free cola or 2 capsules in a random, double-blind, placebo-controlled, within-subjects design. Subjects provided a saliva sample and completed subjective effect scales 15 min before and 30, 60, 90, 120, 180 and 240 min after ingestion. Mean peak saliva caffeine levels did not differ between coffee (9.7 +/- 1.2 micrograms/ml) and cola (9.8 +/- 0.9 micrograms/ml) and appeared to be greater with these beverages than with the capsule (7.8 +/- 0.6 micrograms/ml; p = NS). Saliva caffeine levels peaked at similar times for coffee (42 +/- 5 min) and cola (39 +/- 5 min) but later for capsule (67 +/- 7 min; p = 0.004). There was no main effect of vehicle or interaction of vehicle and drug on magnitude of peak effect or time to peak increase on self-report scales. In summary, peak caffeine absorption, time to peak absorption, and subjective effects do not appear to be influenced by cola vs. coffee vehicle. Perceived differences in the effects of coffee vs. cola may be due to differences in dose, time of day, added sweetener, environmental setting or contingencies.

  8. 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 ...

  9. The marked and rapid therapeutic effect of tofacitinib in combination with subcutaneous methotrexate in a rheumatoid arthritis patient with poor prognostic factors who is resistant to standard disease-modifying antirheumatic drugs and biologicals: A clinical case

    Directory of Open Access Journals (Sweden)

    N. V. Demidova

    2016-01-01

    Full Text Available Today, it is generally accepted that it is necessary to achieve clinical remission in rheumatoid arthritis (RA or as minimum a low disease activity. The paper describes a clinical case of a female patient diagnosed with RA who was observed to have inefficiency of standard disease-modifying antirheumatic therapy with methotrexate 25 mg/week, secondary inefficiency of tumor necrosis factor-α inhibitors (adalimumab, and inefficiency/poor tolerance of the interlukin-6 receptor antagonist tocilizumab. This determined the need to use fofacitinib (TOFA, a drug with another mechanism of action. TOFA is the first agent from a new group of immunomodulatory and anti-inflammatory drugs, intracellular kinase inhibitors. Disease remission could be achieved during therapy with TOFA, which enables one to consider this synthetic drug as a therapy option that potentially competes with therapy with biologicals.

  10. Rapid-scan EPR imaging.

    Science.gov (United States)

    Eaton, Sandra S; Shi, Yilin; Woodcock, Lukas; Buchanan, Laura A; McPeak, Joseph; Quine, Richard W; Rinard, George A; Epel, Boris; Halpern, Howard J; Eaton, Gareth R

    2017-07-01

    In rapid-scan EPR the magnetic field or frequency is repeatedly scanned through the spectrum at rates that are much faster than in conventional continuous wave EPR. The signal is directly-detected with a mixer at the source frequency. Rapid-scan EPR is particularly advantageous when the scan rate through resonance is fast relative to electron spin relaxation rates. In such scans, there may be oscillations on the trailing edge of the spectrum. These oscillations can be removed by mathematical deconvolution to recover the slow-scan absorption spectrum. In cases of inhomogeneous broadening, the oscillations may interfere destructively to the extent that they are not visible. The deconvolution can be used even when it is not required, so spectra can be obtained in which some portions of the spectrum are in the rapid-scan regime and some are not. The technology developed for rapid-scan EPR can be applied generally so long as spectra are obtained in the linear response region. The detection of the full spectrum in each scan, the ability to use higher microwave power without saturation, and the noise filtering inherent in coherent averaging results in substantial improvement in signal-to-noise relative to conventional continuous wave spectroscopy, which is particularly advantageous for low-frequency EPR imaging. This overview describes the principles of rapid-scan EPR and the hardware used to generate the spectra. Examples are provided of its application to imaging of nitroxide radicals, diradicals, and spin-trapped radicals at a Larmor frequency of ca. 250MHz. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. 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 materials. We have used PDS to measure the optical absorption spectra of the conjugated polymers poly(1,4-phenylene-vinylene) (and derivitives) and polydiacetylene-4BCMU in the spectral region from 0.55 eV to 3 eV. Our spectra show that the shape of the absorption edge varies considerably from polymer to polymer, with polydiacetylene-4BCMU having the steepest absorption edge. The minimum absorption coefficients measured varied somewhat with sample age and quality, but were typically in the range 1 cm{sup {minus}1} to 10 cm{sup {minus}1}. In the region below 1 eV, overtones of C-H stretching modes were observed, indicating that further improvements in transparency in this spectral region might be achieved via deuteration of fluorination.

  12. 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...

  13. Buccal bioadhesive drug delivery--a promising option for orally less efficient drugs.

    Science.gov (United States)

    Sudhakar, Yajaman; Kuotsu, Ketousetuo; Bandyopadhyay, A K

    2006-08-10

    Rapid developments in the field of molecular biology and gene technology resulted in generation of many macromolecular drugs including peptides, proteins, polysaccharides and nucleic acids in great number possessing superior pharmacological efficacy with site specificity and devoid of untoward and toxic effects. However, the main impediment for the oral delivery of these drugs as potential therapeutic agents is their extensive presystemic metabolism, instability in acidic environment resulting into inadequate and erratic oral absorption. Parenteral route of administration is the only established route that overcomes all these drawbacks associated with these orally less/inefficient drugs. But, these formulations are costly, have least patient compliance, require repeated administration, in addition to the other hazardous effects associated with this route. Over the last few decades' pharmaceutical scientists throughout the world are trying to explore transdermal and transmucosal routes as an alternative to injections. Among the various transmucosal sites available, mucosa of the buccal cavity was found to be the most convenient and easily accessible site for the delivery of therapeutic agents for both local and systemic delivery as retentive dosage forms, because it has expanse of smooth muscle which is relatively immobile, abundant vascularization, rapid recovery time after exposure to stress and the near absence of langerhans cells. Direct access to the systemic circulation through the internal jugular vein bypasses drugs from the hepatic first pass metabolism leading to high bioavailability. Further, these dosage forms are self-administrable, cheap and have superior patient compliance. Developing a dosage form with the optimum pharmacokinetics is a promising area for continued research as it is enormously important and intellectually challenging. With the right dosage form design, local environment of the mucosa can be controlled and manipulated in order to

  14. Herb-drug interactions.

    Science.gov (United States)

    Fugh-Berman, A

    2000-01-08

    Concurrent use of herbs may mimic, magnify, or oppose the effect of drugs. Plausible cases of herb-drug interactions include: bleeding when warfarin is combined with ginkgo (Ginkgo biloba), garlic (Allium sativum), dong quai (Angelica sinensis), or danshen (Salvia miltiorrhiza); mild serotonin syndrome in patients who mix St John's wort (Hypericum perforatum) with serotonin-reuptake inhibitors; decreased bioavailability of digoxin, theophylline, cyclosporin, and phenprocoumon when these drugs are combined with St John's wort; induction of mania in depressed patients who mix antidepressants and Panax ginseng; exacerbation of extrapyramidal effects with neuroleptic drugs and betel nut (Areca catechu); increased risk of hypertension when tricyclic antidepressants are combined with yohimbine (Pausinystalia yohimbe); potentiation of oral and topical corticosteroids by liquorice (Glycyrrhiza glabra); decreased blood concentrations of prednisolone when taken with the Chinese herbal product xaio chai hu tang (sho-salko-to); and decreased concentrations of phenytoin when combined with the Ayurvedic syrup shankhapushpi. Anthranoid-containing plants (including senna [Cassia senna] and cascara [Rhamnus purshiana]) and soluble fibres (including guar gum and psyllium) can decrease the absorption of drugs. Many reports of herb-drug interactions are sketchy and lack laboratory analysis of suspect preparations. Health-care practitioners should caution patients against mixing herbs and pharmaceutical drugs.

  15. Nanostructured lipid carriers used for oral delivery of oridonin: an effect of ligand modification on absorption.

    Science.gov (United States)

    Zhou, Xiaotong; Zhang, Xingwang; Ye, Yanghuan; Zhang, Tianpeng; Wang, Huan; Ma, Zhiguo; Wu, Baojian

    2015-02-20

    Oridonin (Ori) is a natural compound with notable anti-inflammation and anti-cancer activities. However, therapeutic use of this compound is limited by its poor solubility and low bioavailability. Here a novel biotin-modified nanostructured lipid carrier (NLC) was developed to enhance the bioavailability of Ori. The effect of ligand (biotin) modification on oral absorption of Ori encapsulated in NLCs was also explored. Ori-loaded NLCs (Ori-NLCs) were prepared by the melt dispersion-high pressure homogenization method. Biotin modification of Ori-NLCs was achieved by EDC and NHS in aqueous phase. The obtained biotin-decorated Ori-NLCs (Bio-Ori-NLCs) were 144.9nm in size with an entrapment efficiency of 49.54% and a drug load of 4.81%. Oral bioavailability was enhanced by use of Bio-Ori-NLCs with a relative bioavailability of 171.01%, while the value of non-modified Ori-NLCs was improved to 143.48%. Intestinal perfusion showed that Ori solution unexpectedly exhibited a moderate permeability, indicating that permeability was not a limiting factor of Ori absorption. Ori could be rapidly metabolized that was the main cause of low bioavailability. However, there was a difference in the enhancement of bioavailability between Bio-Ori-NLCs and conventional NLCs. Although severe lipolyses happened both on Bio-Ori-NLCs and non-modified NLCs, the performance of Bio-Ori-NLCs in the bioavailability improvement was more significant. Overall, Bio-Ori-NLCs can further promote the oral absorption of Ori by a ligand-mediated active transport. It may be a promising carrier for the oral delivery of Ori. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Absorption factor for cylindrical samples

    International Nuclear Information System (INIS)

    Sears, V.F.

    1984-01-01

    The absorption factor for the scattering of X-rays or neutrons in cylindrical samples is calculated by numerical integration for the case in which the absorption coefficients of the incident and scattered beams are not equal. An extensive table of values having an absolute accuracy of 10 -4 is given in a companion report [Sears (1983). Atomic Energy of Canada Limited, Report No. AECL-8176]. In the present paper an asymptotic expression is derived for the absorption factor which can be used with an error of less than 10 -3 for most cases of interest in both neutron inelastic scattering and neutron diffraction in crystals. (Auth.)

  17. [Drug induced diarrhea].

    Science.gov (United States)

    Morard, Isabelle; Hadengue, Antoine

    2008-09-03

    Diarrhea is a frequent adverse event involving the most frequently antibiotics, laxatives and NSAI. Drug induced diarrhea may be acute or chronic. It may be due to expected, dose dependant properties of the drug, to immuno-allergic or bio-genomic mechanisms. Several pathophysiological mechanisms have been described resulting in osmotic, secretory or inflammatory diarrhea, shortened transit time, or malabsorption. Histopathological lesions sometimes associated with drug induced diarrhea are usually non specific and include ulcerations, inflammatory or ischemic lesions, fibrous diaphragms, microscopic colitis and apoptosis. The diagnosis of drug induced diarrhea, sometimes difficult to assess, relies on the absence of other obvious causes and on the rapid disappearance of the symptoms after withdrawal of the suspected drug.

  18. Absorption and long term retention of Mn-54 in man

    International Nuclear Information System (INIS)

    Cederblad, A.; Eriksson, R.; Alpsten, M.; Davidsson, L.

    1989-01-01

    The manganese absorption is found to be ≤ 16% after administration of some infant diets as well as from water solutions of manganese. These absorption figures might in some cases be an underestimation of the true initial absorption due to the rapid initial excretion of Mn-54. This means that both the often quoted figure for manganese absorption in humans, 3.0±0.5% and the value 10% used by ICRP 1979 are underestimations of the fractional absorption of manganese under some circumstances. The long term retention curve obtained, where the ratio between retention day 200 and day 30 had a mean value of 0.19 (range 0.10-0.35), could be compared to the two-component exponential function used by ICRP 1979 based on studies by Mahoney and Small 1968 where the corresponding ratio is 0.045. In the study by Mahoney and Small Mn-54 retention was studied after intravenous administration. We have earlier observed a difference between the metabolic handling of Mn-54 introduced orally and intravenously in man. Another model proposed by Caughtrey and Thorne 1983 consisting of a three component exponential function is in better agreement with our measurements and gives the ratio 0.22. The ICRP model for dose calculations tends to underestimate fractional absorption as well as long term retention of manganese. (orig./HP)

  19. Drug allergies

    Science.gov (United States)

    Allergic reaction - drug (medication); Drug hypersensitivity; Medication hypersensitivity ... A drug allergy involves an immune response in the body that produces an allergic reaction to a medicine. The first time ...

  20. Study Drugs

    Science.gov (United States)

    ... to quit, they may have withdrawal symptoms like depression, thoughts of suicide, intense drug cravings, sleep problems, and fatigue. The health risks aren't the only downside to study drugs. Students caught with illegal prescription drugs may get suspended ...

  1. Drug Facts

    Medline Plus

    Full Text Available ... symptoms 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 Hard to ...

  2. Drug Facts

    Medline Plus

    Full Text Available ... Other Effects on the Body Drug Use Hurts Brains Drug Use and Mental Health Problems Often Happen ... to prescription drugs. The addiction slowly took over his life. I need different people around me. To ...

  3. Drug Reactions

    Science.gov (United States)

    ... problem is interactions, which may occur between Two drugs, such as aspirin and blood thinners Drugs and food, such as statins and grapefruit Drugs and supplements, such as ginkgo and blood thinners ...

  4. Drug Facts

    Science.gov (United States)

    ... Makes Someone More Likely to Get Addicted to Drugs? Does Addiction Run in Families? Why Is It So Hard ... the text to you. This website talks about drug abuse, addiction, and treatment. Watch Videos Information About Drugs Alcohol ...

  5. 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.

  6. OZONE ABSORPTION IN RAW WATERS

    Directory of Open Access Journals (Sweden)

    LJILJANA TAKIĆ

    2008-03-01

    Full Text Available The ozone absorption in raw water entering the main ozonization step at the Belgrade drinking water supply plant was investigated in a continuous stirred tank reactor (CSTR. A slow chemical reaction rate of dissolved ozone and pollutants present in raw water have been experimentally determined. The modified Hatta number was defined and calculated as a criterion which determines whether and to which extent the reactions of ozone and pollutants influence the rate of the pure physical ozone absorption.

  7. Microwaves absorption in superconducting materials

    International Nuclear Information System (INIS)

    Biasi, R.S. de; Fernandes, A.A.R.; Pereira, R.F.R.

    1989-01-01

    Microwaves absorption measures in two superconductors ceramics systems, Y-Ba-Cu-O and Bi-Sr-Ca-Cu-O are compared with similars datas obtained in the same band of temperature by a conventional method, mutual inductance. The results suggest that the microwaves absorption can be used as single and non-destructive method for investigating the properties of ceramics superconductors. (C.G.C.) [pt

  8. 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.

  9. Ultrasonic absorption in solid specimens

    International Nuclear Information System (INIS)

    Siwabessy, P.J. W.; Stewart, G.A.

    1996-01-01

    As part of a project to measure the absorption of high frequency (50 - 500 kHz) sonar signals in warm sea-water, a laboratory apparatus has been constructed and tested against room temperature distilled water and various solutions of MgSO 4 (chemical relaxation of MgSO 4 is the major contribution to absorption below 200 kHz). The technique involves monitoring the decay of an acoustic signal for different sizes of vessels of water suspended in an evacuated chamber. So far, all containing vessels used have been spherical in shape. Extrapolation of the results to infinite volume yields the absorption due to the water alone. In order to accommodate variations in temperature and pressure, and to make the system more robust (e.g. for ship deck usage), it is desirable to employ stainless steel vessels. However, it was found that the quality of the data was greatly improved when pyrex glass spheres were used. The stainless steel spheres were manufactured by welding together mechanically spun hemispheres. The linear frequency dependence characteristic of acoustic absorption in solids was observed (in contrast to the quadratic frequency dependence of acoustic absorption in water), and the acoustic absorption was found to depend strongly on the thermal history of the steel

  10. Evaluation of an in vitro faecal degradation method for early assessment of the impact of colonic degradation on colonic absorption in humans.

    Science.gov (United States)

    Tannergren, Christer; Borde, Anders; Boreström, Cecilia; Abrahamsson, Bertil; Lindahl, Anders

    2014-06-16

    The objective of this study was to develop and evaluate an in vitro method to investigate bacterial-mediated luminal degradation of drugs in colon in humans. This would be a valuable tool for the assessment of drug candidates during early drug development, especially for compounds intended to be developed as oral extended release formulations. Freshly prepared faecal homogenate from healthy human volunteers (n=3-18), dog (n=6) and rat (colon and caecal content, n=3) was homogenised with 3.8 parts (w/w) physiological saline under anaerobical conditions. Four model compounds (almokalant, budesonide, ximelagatran and metoprolol) were then incubated (n=3-18) separately in the human faecal homogenate for up to 120min at 37°C. In addition, ximelagatran was also incubated in the faecal or colonic content from dog and rat. The mean (±SD) in vitro half-life for almokalant, budesonide and ximelagatran was 39±1, 68±21 and 26±12min, respectively, in the human faecal homogenate. Metoprolol was found to be stable in the in vitro model. The in vitro degradation data was then compared to literature data on fraction absorbed after direct colon administration in humans. The percentage of drug remaining after 60min of in vitro incubation correlated (R(2)=0.90) with the fraction absorbed from colon in humans. The mean in vitro half-life of ximelagatran was similar in human faeces (26±12min) and rat colon content (34±31min), but significantly (pdegradation in vivo was rapidly degraded in the faecal homogenates as well as quantitatively since a correlation was established between percentage degraded in vitro at 60min and fraction absorbed in the colon for the model drugs, which have no other absorption limiting properties. Also, the method is easy to use from a technical point of view, which suggests that the method is suitable for use in early assessment of colonic absorption of extended release formulation candidates. Further improvement of the confidence in the use of the

  11. 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,

  12. Emerging Frontiers in Drug Delivery.

    Science.gov (United States)

    Tibbitt, Mark W; Dahlman, James E; Langer, Robert

    2016-01-27

    Medicine relies on the use of pharmacologically active agents (drugs) to manage and treat disease. However, drugs are not inherently effective; the benefit of a drug is directly related to the manner by which it is administered or delivered. Drug delivery can affect drug pharmacokinetics, absorption, distribution, metabolism, duration of therapeutic effect, excretion, and toxicity. As new therapeutics (e.g., biologics) are being developed, there is an accompanying need for improved chemistries and materials to deliver them to the target site in the body, at a therapeutic concentration, and for the required period of time. In this Perspective, we provide an historical overview of drug delivery and controlled release followed by highlights of four emerging areas in the field of drug delivery: systemic RNA delivery, drug delivery for localized therapy, oral drug delivery systems, and biologic drug delivery systems. In each case, we present the barriers to effective drug delivery as well as chemical and materials advances that are enabling the field to overcome these hurdles for clinical impact.

  13. Rapid Quantitation of Furanocoumarins and Flavonoids in Grapefruit Juice using Ultra-Performance Liquid Chromatography.

    Science.gov (United States)

    Vandermolen, Karen M; Cech, Nadja B; Paine, Mary F; Oberlies, Nicholas H

    2013-01-01

    Grapefruit juice can increase or decrease the systemic exposure of myriad oral medications, leading to untoward effects or reduced efficacy. Furanocoumarins in grapefruit juice have been established as inhibitors of cytochrome P450 3A (CYP3A)-mediated metabolism and P-glycoprotein (P-gp)-mediated efflux, while flavonoids have been implicated as inhibitors of organic anion transporting polypeptide (OATP)-mediated absorptive uptake in the intestine. The potential for drug interactions with a food product necessitates an understanding of the expected concentrations of a suite of structurally diverse and potentially bioactive compounds. Develop methods for the rapid quantitation of two furanocoumarins (bergamottin and 6',7'-dihydroxybergamottin) and four flavonoids (naringin, naringenin, narirutin and hesperidin) in five grapefruit juice products using ultra-performance liquid chromatography (UPLC). Grapefruit juice products were extracted with ethyl acetate; the concentrated extract was analysed by UPLC using acetonitrile:water gradients and a C18 -column. Analytes were detected using a photodiode array detector, set at 250 nm (furanocoumarins) and 310 nm (flavonoids). Intraday and interday precision and accuracy and limits of detection and quantitation were determined. Rapid (0.999. Considerable between-juice variation in the concentrations of these compounds was observed, and the quantities measured were in agreement with the concentrations published in HPLC studies. These analytical methods provide an expedient means to quantitate key furanocoumarins and flavonoids in grapefruit juice and other foods used in dietary substance-drug interaction studies. Copyright © 2013 John Wiley & Sons, Ltd.

  14. Ultra-Short Laser Absorption In Solid Targets

    International Nuclear Information System (INIS)

    Harfouche, A.; Bendib, A.

    2008-01-01

    With the rapid development and continuously improving technology of subpicosecond laser pulse generation, new interesting physical problems are now investigated. Among them the laser light absorption in solid targets. During the interaction with solid targets, high intensity laser pulses are absorbed by electrons in optical skin depths, leading to rapid ionization before that significant ablation of solid material takes place. The ultra-short laser is absorbed in the overdense plasma through the electron-ion collisions (normal skin effect) or collisionless mechanisms (anomalous skin effect or sheath inverse bremsstrahlung). These two regimes depend on the laser intensity, the plasma temperature and the ionization state Z. In this work we solve numerically the Fokker-Planck equation to compute the electron distribution function in the skin layer. In the second step we compute the surface impedance and we deduce the absorption coefficient.

  15. Drug Facts

    Medline Plus

    Full Text Available ... 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? ...

  16. Drug Facts

    Medline Plus

    Full Text Available ... 4357) at any time to find drug treatment centers near you. I want my daughter to avoid drugs. "Debbie" has been drug-free for years. She wants her daughter to stay away from drugs. But she's afraid ...

  17. Absorption and Clearance of Pharmaceutical Aerosols in the Human Nose: Effects of Nasal Spray Suspension Particle Size and Properties.

    Science.gov (United States)

    Rygg, Alex; Hindle, Michael; Longest, P Worth

    2016-04-01

    The objective of this study was to use a recently developed nasal dissolution, absorption, and clearance (DAC) model to evaluate the extent to which suspended drug particle size influences nasal epithelial drug absorption for a spray product. Computational fluid dynamics (CFD) simulations of mucociliary clearance and drug dissolution were used to calculate total and microscale epithelial absorption of drug delivered with a nasal spray pump. Ranges of suspended particle sizes, drug solubilities, and partition coefficients were evaluated. Considering mometasone furoate as an example, suspended drug particle sizes in the range of 1-5 μm did not affect the total nasal epithelial uptake. However, the microscale absorption of suspended drug particles with low solubilities was affected by particle size and this controlled the extent to which the drug penetrated into the distal nasal regions. The nasal-DAC model was demonstrated to be a useful tool in determining the nasal exposure of spray formulations with different drug particle sizes and solubilities. Furthermore, the model illustrated a new strategy for topical nasal drug delivery in which drug particle size is selected to increase the region of epithelial surface exposure using mucociliary clearance while minimizing the drug dose exiting the nasopharynx.

  18. 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.

  19. Absorption and metabolism of xanthophylls.

    Science.gov (United States)

    Kotake-Nara, Eiichi; Nagao, Akihiko

    2011-01-01

    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.

  20. Intestinal transport of gentamicin with a novel, glycosteroid drug transport agent

    Science.gov (United States)

    Axelrod, H. R.; Kim, J. S.; Longley, C. B.; Lipka, E.; Amidon, G. L.; Kakarla, R.; Hui, Y. W.; Weber, S. J.; Choe, S.; Sofia, M. J.

    1998-01-01

    PURPOSE: The objective was to investigate the ability of a glycosteroid (TC002) to increase the oral bioavailability of gentamicin. METHODS: Admixtures of gentamicin and TC002 were administered to the rat ileum by injection and to dogs by ileal or jejunal externalized ports, or PO. Bioavailability of gentamicin was determined by HPLC. 3H-TC002 was injected via externalized cannulas into rat ileum or jejunum, or PO and its distribution and elimination was determined. The metabolism of TC002 in rats was evaluated by solid phase extraction and HPLC analysis of plasma, urine and feces following oral or intestinal administration. RESULTS: The bioavailability of gentamicin was substantially increased in the presence of TC002 in both rats and dogs. The level of absorption was dependent on the concentration of TC002 and site of administration. Greatest absorption occurred following ileal orjejunal administration. TC002 was significantly more efficacious than sodium taurocholate, but similar in cytotoxicity. TC002 remained primarily in the GI tract following oral or intestinal administration and cleared rapidly from the body. It was only partly metabolized in the GI tract, but was rapidly and completely converted to its metabolite in plasma and urine. CONCLUSIONS: TC002 shows promise as a new drug transport agent for promoting intestinal absorption of polar molecules such as gentamicin.

  1. Comparison of systemic absorption between ofloxacin ophthalmic in situ gels and ofloxacin conventional ophthalmic solutions administration to rabbit eyes by HPLC-MS/MS.

    Science.gov (United States)

    Li, Jiawei; Zhao, Hainan; Okeke, Chukwunweike Ikechukwu; Li, Lin; Liu, Zhidong; Yin, Zhongpeng; Zhuang, Pengwei; Sun, Jingtong; Wu, Tao; Wang, Meng; Li, Nan; Pi, Jiaxin; Zhang, Qian; Zhang, Rui; Ma, Li; Pang, Xiaochen; Liu, Zhanbiao; Zhang, Li; Fan, Lili

    2013-06-25

    In recent years, many pharmaceutical scientists have focused on developing the in situ gel-forming systems to overcome the poor bioavailability and therapeutic response exhibited by conventional ophthalmic solutions due to rapid pre-corneal elimination of the drug. The present work was to compare the systemic absorptions of ophthalmic ofloxacin in situ gel with the conventional ofloxacin eye drop after topical instillation to rabbit eyes by HPLC-MS/MS method and also determine the relative contribution of the nasal and the conjunctival mucosae to systemic ofloxacin absorption following topical instillation. The systemic AUC, Cmax, Tmax and Ke for ophthalmic in situ gel and ophthalmic solution after ocular instillation were 202.63±118.85 and 202.25±57.74 ng mL(-1) h, 54.22±28.31 and 48.4±25.97 ng mL(-1), 1.08±0.20 and 1.25±0.88 h, 0.0576±0.0207 and 0.0388±0.0248, respectively. And the values for the ratios of the AUC of anterior chamber of rabbit eye to blood plasma, AUCac/AUCpl, for ofloxacin conventional eye drop and in situ gel were 0.25 and 0.52, respectively. Statistic results showed that there was no significant difference in systemic absorption between the test groups and the reference groups (P>0.05) as both formulations have an AUCsa/AUCpl of 0.35. Therefore, the ophthalmic in situ gel may not decrease the drugs systemic absorption when administered in an equivalent dose as ophthalmic solutions into the rabbit eyes. Copyright © 2013 Elsevier B.V. All rights reserved.

  2. Rapid assessment of sexual behavior, drug use, human immunodeficiency virus, and sexually transmitted diseases in northern thai youth using audio-computer-assisted self-interviewing and noninvasive specimen collection.

    Science.gov (United States)

    van Griensven, F; Supawitkul, S; Kilmarx, P H; Limpakarnjanarat, K; Young, N L; Manopaiboon, C; Mock, P A; Korattana, S; Mastro, T D

    2001-07-01

    Drug use, unwanted pregnancy, human immunodeficiency virus (HIV) infection, and sexually transmitted diseases are serious health problems among Thai youth. The gravity of these problems demands high-quality data to direct public health policy and prevention programs. Previous studies of stigmatized behaviors have been hampered by participation bias and underreporting. To evaluate sexual behavior, disease, and drug use, we used audio-computer-assisted self-interviewing (ACASI) and noninvasive specimen collection methods. We also evaluated effectiveness of these methods in minimizing participation bias and underreporting. In late 1999, students aged 15 to 21 years attending 3 vocational schools were invited to participate in a cross-sectional survey. Consenting students completed a classroom-based ACASI interview using a confidential code number system. Oral fluid specimens were tested for HIV antibodies, and urine was tested for chlamydial and gonococcal nucleic acids, methamphetamines, and opiates. Of 1736 invited students, 1725 (99%) agreed to participate. Of these, 48% of the male students and 43% of the female students reported ever having had sexual intercourse. Overall, the mean number of lifetime sexual partners was 4.6 among male participants (median: 2) and 2.8 among female participants (median: 1). Consistent use of condoms with steady partners was reported by 16% of male participants and 11% of female participants who had such partners. Of all male participants, 7% had ever paid for sex, 3% had ever sold sex, and 7% had ever been coerced to have sex. Of all female participants, 3% had ever sold sex and 21% had ever been coerced to have sex. Among women with a history of sexual intercourse, 27% reported at least 1 pregnancy. Of these pregnancies, 83% were terminated. Among those with sexual intercourse experience, the prevalence of HIV infection was 0.5%; of infection with Neisseria gonorrhoeae, 0.4%; and of infection with Chlamydia trachomatis, 5%. Twenty

  3. Absorption properties of identical atoms

    International Nuclear Information System (INIS)

    Sancho, Pedro

    2013-01-01

    Emission rates and other optical properties of multi-particle systems in collective and entangled states differ from those in product ones. We show the existence of similar effects in the absorption probabilities for (anti)symmetrized states of two identical atoms. The effects strongly depend on the overlapping between the atoms and differ for bosons and fermions. We propose a viable experimental verification of these ideas. -- Highlights: •The absorption rates of a pair of identical atoms in product and (anti)symmetrized states are different. •The modifications of the optical properties are essentially determined by the overlapping between the atoms. •The absorption properties differ, in some cases, for bosons and fermions

  4. Architecture for Absorption Based Heaters

    Science.gov (United States)

    Moghaddam, Saeed; Chugh, Devesh

    2018-04-24

    An absorption based heater is constructed on a fluid barrier heat exchanging plate such that it requires little space in a structure. The absorption based heater has a desorber, heat exchanger, and absorber sequentially placed on the fluid barrier heat exchanging plate. The vapor exchange faces of the desorber and the absorber are covered by a vapor permeable membrane that is permeable to a refrigerant vapor but impermeable to an absorbent. A process fluid flows on the side of the fluid barrier heat exchanging plate opposite the vapor exchange face through the absorber and subsequently through the heat exchanger. The absorption based heater can include a second plate with a condenser situated parallel to the fluid barrier heat exchanging plate and opposing the desorber for condensation of the refrigerant for additional heating of the process fluid.

  5. Mercury absorption in aqueous hypochlorite

    International Nuclear Information System (INIS)

    Zhao, L.L.; Rochelle, G.T.

    1999-01-01

    The absorption of elemental Hg vapor into aqueous hypochlorite was measured in a stirred tank reactor at 25 and 55C. NaOCl strongly absorbs Hg even at high pH. Low pH, high Cl - and high-temperature favor mercury absorption. Aqueous free Cl 2 was the active species that reacted with mercury. However, chlorine desorption was evident at high Cl - and pH 15 M -1 s -1 at 25C and 1.4x10 17 M -1 s -1 at 55C. Gas-phase reaction was observed between Hg and Cl 2 on apparatus surfaces. Strong mercury absorption in water was also detected with Cl 2 present. Results indicate that the chlorine concentration, moisture, and surface area contribute positively to mercury removal. (Copyright (c) 1999 Elsevier Science B.V., Amsterdam. All rights reserved.)

  6. 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......, where it serves as a storage molecule for phosphorous. Phytic acid is also associated with minerals. The minerals are bound by chelation to the negatively charged phosphate groups in phytic acid. Phytases catalyse the dephosphorylation of phytic acid, thus releasing bound minerals to make them available...... for absorption. This article presents research on phytase catalysis in gastric conditions and considers potential benefits and drawbacks for using phytases as a food supplement....

  7. The effects of three absorption-modifying critical excipients on the in vivo intestinal absorption of six model compounds in rats and dogs.

    Science.gov (United States)

    David, Dahlgren; Carl, Roos; Pernilla, Johansson; Christer, Tannergren; Anders, Lundqvist; Peter, Langguth; Markus, Sjöblom; Erik, Sjögren; Hans, Lennernäs

    2018-05-11

    Pharmaceutical excipients that may affect gastrointestinal (GI) drug absorption are called critical pharmaceutical excipients (CPEs), or absorption-modifying excipients (AMEs) if they act by altering the integrity of the intestinal epithelial cell membrane. Some of these excipients increase intestinal permeability, and subsequently the absorption and bioavailability of the drug. This could have implications for both the assessment of bioequivalence and the efficacy of the absorption-enhancing drug delivery system. The absorption-enhancing effects of AMEs/CPEs with different mechanisms (chitosan, sodium caprate, sodium dodecyl sulfate (SDS)) have previously been evaluated in the rat single-pass intestinal perfusion (SPIP) model. However, it remains unclear whether these SPIP data are predictive in a more in vivo like model. The same excipients were in this study evaluated in rat and dog intraintestinal bolus models. SDS and chitosan did exert an absorption-enhancing effect in both bolus models, but the effect was substantially lower than those observed in the rat SPIP model. This illustrates the complexity of the AME/CPE effects, and indicates that additional GI physiological factors need to be considered in their evaluation. We therefore recommend that AME/CPE evaluations obtained in transit-independent, preclinical permeability models (e.g. Ussing, SPIP) should be verified in animal models better able to predict in vivo relevant GI effects, at multiple excipient concentrations. Copyright © 2018. Published by Elsevier B.V.

  8. Scramjet Performance Assessment Using Water Absorption Diagnostics (U)

    Science.gov (United States)

    Cavolowsky, John A.; Loomis, Mark P.; Deiwert, George

    1995-01-01

    Simultaneous multiple path measurements of temperature and H2O concentration will be presented for the AIMHYE test entries in the NASA Ames 16-Inch Shock Tunnel. Monitoring the progress of high temperature chemical reactions that define scramjet combustor efficiencies is a task uniquely suited to nonintrusive optical diagnostics. One application strategy to overcome the many challenges and limitations of nonintrusive measurements is to use laser absorption spectroscopy coupled with optical fibers. Absorption spectroscopic techniques with rapidly tunable lasers are capable of making simultaneous measurements of mole fraction, temperature, pressure, and velocity. The scramjet water absorption diagnostic was used to measure combustor efficiency and was compared to thrust measurements using a nozzle force balance and integrated nozzle pressures to develop a direct technique for evaluating integrated scramjet performance. Tests were initially performed with a diode laser tuning over a water absorption feature at 1391.7 nm. A second diode laser later became available at a wavelength near 1343.3 nm covering an additional water absorption feature and was incorporated in the system for a two-wavelength technique. Both temperature and mole fraction can be inferred from the lineshape analysis using this approach. Additional high temperature spectroscopy research was conducted to reduce uncertainties in the scramjet application. The lasers are optical fiber coupled to ports at the combustor exit and in the nozzle region. The output from the two diode lasers were combined in a single fiber, and the resultant two-wavelength beam was subsequently split into four legs. Each leg was directed through 60 meters of optical fiber to four combustor exit locations for measurement of beam intensity after absorption by the water within the flow. Absorption results will be compared to 1D combustor analysis using RJPA and nozzle CFD computations as well as to data from a nozzle metric

  9. 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.

  10. 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...

  11. The fate of calcium carbonate nanoparticles administered by oral route: absorption and their interaction with biological matrices

    Directory of Open Access Journals (Sweden)

    Lee JA

    2015-03-01

    Full Text Available Jeong-A Lee,1,* Mi-Kyung Kim,1,* Hyoung-Mi Kim,2,* Jong Kwon Lee,3 Jayoung Jeong,4 Young-Rok Kim,5 Jae-Min Oh,2 Soo-Jin Choi1 1Department of Food Science and Technology, Seoul Women’s University, Seoul, Republic of Korea; 2Department of Chemistry and Medical Chemistry, College of Science and Technology, Yonsei University, Wonju, Republic of Korea; 3Hazard Substances Analysis Division, Gwangju Regional Food and Drug Administration, Ministry of Food and Drug Safety, Gwangju, Republic of Korea; 4Toxicological Research Division, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, Chungcheongbuk-do, Republic of Korea; 5Department of Food Science and Biotechnology, Kyung Hee University, Yongin, Republic of Korea *These authors contributed equally to this work Background: Orally administered particles rapidly interact with biological fluids containing proteins, enzymes, electrolytes, and other biomolecules to eventually form particles covered by a corona, and this corona potentially affects particle uptake, fate, absorption, distribution, and elimination in vivo. This study explored relationships between the biological interactions of calcium carbonate particles and their biokinetics.Methods: We examined the effects of food grade calcium carbonates of different particle size (nano [N-Cal] and bulk [B-Cal]: specific surface areas of 15.8 and 0.83 m2/g, respectively on biological interactions in in vitro simulated physiological fluids, ex vivo biofluids, and in vivo in gastrointestinal fluid. Moreover, absorption and tissue distribution of calcium carbonates were evaluated following a single dose oral administration to rats.Results: N-Cal interacted more with biomatrices than bulk materials in vitro and ex vivo, as evidenced by high fluorescence quenching ratios, but it did not interact more actively with biomatrices in vivo. Analysis of coronas revealed that immunoglobulin, apolipoprotein, thrombin, and fibrinogen

  12. 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

  13. Therapeutic Drug Monitoring in Rheumatic Diseases

    Directory of Open Access Journals (Sweden)

    NG Hoi-Yan Alexandra

    2016-12-01

    Full Text Available The ultimate goal of treating rheumatic disease is to achieve rapid suppression of inflammation, while at the same time minimizing the toxicities from rheumatic drugs. Different patients have different individual pharmacokinetics that can affect the drug level. Moreover, different factors, such as renal function, age or even different underlying diseases, can affect the drug level. Therefore, giving the same dosage of drugs to different patients may result in different drug levels. This article will review the usefulness of therapeutic drug monitoring in maximizing drug efficacy, while reducing the risk of toxicities in Hydroxychloroquine, Mycophenolate Mofetil, Tacrolimus and Tumor Necrosis Factor inhibitors (TNF Inhibitors.

  14. Substance use - prescription drugs

    Science.gov (United States)

    Substance use disorder - prescription drugs; Substance abuse - prescription drugs; Drug abuse - prescription drugs; Drug use - prescription drugs; Narcotics - substance use; Opioid - substance use; Sedative - substance ...

  15. Rapid Sampling from Sealed Containers

    International Nuclear Information System (INIS)

    Johnston, R.G.; Garcia, A.R.E.; Martinez, R.K.; Baca, E.T.

    1999-01-01

    The authors have developed several different types of tools for sampling from sealed containers. These tools allow the user to rapidly drill into a closed container, extract a sample of its contents (gas, liquid, or free-flowing powder), and permanently reseal the point of entry. This is accomplished without exposing the user or the environment to the container contents, even while drilling. The entire process is completed in less than 15 seconds for a 55 gallon drum. Almost any kind of container can be sampled (regardless of the materials) with wall thicknesses up to 1.3 cm and internal pressures up to 8 atm. Samples can be taken from the top, sides, or bottom of a container. The sampling tools are inexpensive, small, and easy to use. They work with any battery-powered hand drill. This allows considerable safety, speed, flexibility, and maneuverability. The tools also permit the user to rapidly attach plumbing, a pressure relief valve, alarms, or other instrumentation to a container. Possible applications include drum venting, liquid transfer, container flushing, waste characterization, monitoring, sampling for archival or quality control purposes, emergency sampling by rapid response teams, counter-terrorism, non-proliferation and treaty verification, and use by law enforcement personnel during drug or environmental raids

  16. Factors affecting the absorption and excretion of lead in the rat

    International Nuclear Information System (INIS)

    Conrad, M.E.; Barton, J.C.

    1978-01-01

    A reliable method for studying lead absorption and excretion in rats is described. Lead absorption occurs primarily in the duodenum where lead enters the epithelial mucosal cells. There is a relative mucosal block for lead with increasing intraluminal doses. Certain substances which bind lead and increase its solubility enhance its absorption. Iron, zinc, and calcium decrease the absorption of lead without affecting its solubility, probably by competing for shared absorptive receptors in the intestinal mucosa. The total body burden of lead does not affect lead absorption. Thus, lead does not have a feedback mechanism which limits absorption. Lead absorption is increased during rapid periods of growth and in iron-deficient animals. It is diminished with starvation and in iron-overloaded animals. The excretion and kinetics of tracer doses of radiolead were quantified. Erythrocytes seem to serve an important role in transport. Excretion occurs in urine and stool. Bile is an important route of excretion in the gut. Although most of a tracer dose is rapidly excreted, the excretory process is limited permitting lead accumulation primarily in bone

  17. Investigating broadband acoustic adsorption using rapid manufacturing

    Science.gov (United States)

    Godbold, O.

    The reduction of nuisance noise and the removal of unwanted sound modes within a room or component enclosure-area can be accomplished through the use of acoustic absorbers. Sound absorption can be achieved through conversion of the kinetic energy associated with pressure waves, into heat energy via viscous dissipation. This occurs within open porous materials, or by utilising resonant effects produced using simple cavity and orifice configurations. The manufacture of traditional porous and resonant absorbers is commonly realised using basic manufacturing techniques. These techniques restrict the geometry of a given resonant construction, and limit the configuration of porous absorbers. The aim of this work is to exploit new and emerging capabilities of Rapid Manufacturing (RM) to produce components with geometrical freedom, and apply it to the development of broadband acoustic absorption. New and novel absorber geometric configurations are identified and their absorption performance is determined. The capabilities and limitations of RM processes in reproducing these configurations are demonstrated. The geometric configuration of RM resonant absorbers is investigated. Cavity modifications aimed at damping the resonant effect by restricting the motion of cavity air, and adding increased viscous resistance are explored. Modifications relating to cavity shape, the addition of internal perforations and increased cavity surface area have all been shown to add acoustic resistance, thereby increasing the bandwidth of absorption. Decreasing the hydraulic radius of the cavity cross section and reducing internal feature dimensions provide improved resistance over conventional configurations..

  18. Antiretroviral therapy: current drugs.

    Science.gov (United States)

    Pau, Alice K; George, Jomy M

    2014-09-01

    The rapid advances in drug discovery and the development of antiretroviral therapy is unprecedented in the history of modern medicine. The administration of chronic combination antiretroviral therapy targeting different stages of the human immunodeficiency virus' replicative life cycle allows for durable and maximal suppression of plasma viremia. This suppression has resulted in dramatic improvement of patient survival. This article reviews the history of antiretroviral drug development and discusses the clinical pharmacology, efficacy, and toxicities of the antiretroviral agents most commonly used in clinical practice to date. Published by Elsevier Inc.

  19. Konference Distillation and Absorption 2010

    Czech Academy of Sciences Publication Activity Database

    Bendová, Magdalena

    2009-01-01

    Roč. 103, č. 10 (2009), s. 862 ISSN 0009-2770 R&D Projects: GA MŠk LA320 Institutional research plan: CEZ:AV0Z40720504 Keywords : conference * announcement * distillation and absorption Subject RIV: CF - Physical ; Theoretical Chemistry

  20. Gamm-ray absorption techniques

    International Nuclear Information System (INIS)

    Charlton, J.S.

    1986-01-01

    In this chapter the principles of gamma-ray absorption are described and important applications in plant and process techniques such as measurement of thickness of deposits on pipes, checking for voids in concrete, metal corrosion, measurement of the density of materials inside vessels in industrial radiography are discussed. (U.K.)

  1. Emission and absorption of radiation

    International Nuclear Information System (INIS)

    Fetter, S.

    1992-01-01

    A full understanding of fissile-material detection requires a solid knowledge of nuclear physics, especially the emission and absorption of radiation. The purpose of this paper is therefore to give a brief explanation of these processes so that the reader can better understand the assumptions leading to the results in the main text

  2. 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

  3. 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,...

  4. Drug Facts

    Medline Plus

    Full Text Available ... abuse, addiction, and treatment. Watch Videos Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine Other Drugs You can ...

  5. Prescription Drugs

    Science.gov (United States)

    ... different competition is going on: the National Football League (NFL) vs. drug use. Read More » 92 Comments ... Future survey highlights drug use trends among the Nation’s youth for marijuana, alcohol, cigarettes, e-cigarettes (e- ...

  6. Drug Facts

    Medline Plus

    Full Text Available ... abuse, addiction, and treatment. Watch Videos Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth ... 662-HELP (4357) at any time to find drug treatment centers near you. I want my daughter ...

  7. Drug Facts

    Medline Plus

    Full Text Available ... form Search Menu Home Drugs That People Abuse Alcohol Facts Bath Salts Facts Cocaine (Coke, Crack) Facts ... addiction, and treatment. Watch Videos Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain ...

  8. Drug Facts

    Medline Plus

    Full Text Available ... Ice) Facts Pain Medicine (Oxy, Vike) Facts Spice (K2) Facts Tobacco and Nicotine Facts Other Drugs of ... Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine Other Drugs You can call 1- ...

  9. Drug Control

    Science.gov (United States)

    Leviton, Harvey S.

    1975-01-01

    This article attempts to assemble pertinent information about the drug problem, particularily marihuana. It also focuses on the need for an educational program for drug control with the public schools as the main arena. (Author/HMV)

  10. Drug Facts

    Medline Plus

    Full Text Available ... Crank, Ice) Facts Pain Medicine (Oxy, Vike) Facts Spice (K2) Facts Tobacco and Nicotine Facts Other Drugs ... Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine Other Drugs You can call ...

  11. Drug Facts

    Medline Plus

    Full Text Available ... Nicotine Facts Other Drugs of Abuse What is Addiction? What are some signs and symptoms of someone ... use problem? How Does Drug Use Become an Addiction? What Makes Someone More Likely to Get Addicted ...

  12. Drug Facts

    Medline Plus

    Full Text Available ... Numbers and Websites Search Share Listen English Español Information about this page Click on the button that ... about drug abuse, addiction, and treatment. Watch Videos Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana ...

  13. Drug Facts

    Medline Plus

    Full Text Available ... Home Drugs That People Abuse Alcohol Facts Bath Salts Facts Cocaine (Coke, Crack) Facts Heroin (Smack, Junk) ... treatment. Watch Videos Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice ( ...

  14. Drug Facts

    Medline Plus

    Full Text Available ... call 1-800-662-HELP (4357) at any time to find drug treatment centers near you. I ... The National Institute on Drug Abuse (NIDA) is part of the National Institutes of Health (NIH) , the ...

  15. Orphan drugs

    OpenAIRE

    Goločorbin-Kon, Svetlana; Vojinović, Aleksandra; Lalić-Popović, Mladena; Pavlović, Nebojša; Mikov, Momir

    2013-01-01

    Introduction. Drugs used for treatment of rare diseases are known worldwide under the term of orphan drugs because pharmaceutical companies have not been interested in ”adopting” them, that is in investing in research, developing and producing these drugs. This kind of policy has been justified by the fact that these drugs are targeted for small markets, that only a small number of patients is available for clinical trials, and that large investments are required for the development of ...

  16. Converting Sabine absorption coefficients to random incidence absorption coefficients

    DEFF Research Database (Denmark)

    Jeong, Cheol-Ho

    2013-01-01

    are suggested: An optimization method for the surface impedances for locally reacting absorbers, the flow resistivity for extendedly reacting absorbers, and the flow resistance for fabrics. With four porous type absorbers, the conversion methods are validated. For absorbers backed by a rigid wall, the surface...... coefficients to random incidence absorption coefficients are proposed. The overestimations of the Sabine absorption coefficient are investigated theoretically based on Miki's model for porous absorbers backed by a rigid wall or an air cavity, resulting in conversion factors. Additionally, three optimizations...... impedance optimization produces the best results, while the flow resistivity optimization also yields reasonable results. The flow resistivity and flow resistance optimization for extendedly reacting absorbers are also found to be successful. However, the theoretical conversion factors based on Miki's model...

  17. Drug Testing

    Science.gov (United States)

    ... testing, substance abuse testing, toxicology screen, tox screen, sports doping tests What is it used for? Drug screening is used to find out whether or not a person has taken a certain drug or drugs. It ... Sports organizations. Professional and collegiate athletes usually need to ...

  18. 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 Listen English Español Information about this page ...

  19. Drug Facts

    Medline Plus

    Full Text Available ... can call 1-800-662-HELP (4357) at any time to find drug treatment centers near you. I want my daughter to avoid drugs. "Debbie" has been drug-free for years. She wants her daughter to stay away from ...

  20. Drug Facts

    Medline Plus

    Full Text Available ... the computer will read the text to you. This website talks about drug abuse, addiction, and treatment. Watch Videos ... I want my daughter to avoid drugs. "Debbie" has been drug-free for years. She wants her daughter to stay away from ...