WorldWideScience

Sample records for drugs investigational

  1. 75 FR 32482 - Investigational New Drug Applications; Co-development of Investigational Drugs

    Science.gov (United States)

    2010-06-08

    ... HUMAN SERVICES Food and Drug Administration Investigational New Drug Applications; Co-development of Investigational Drugs AGENCY: Food and Drug Administration, HHS. ACTION: Notice; establishment of docket; request for comments. SUMMARY: The Food and Drug Administration (FDA) is establishing a public docket...

  2. Disposition and Metabolism of Investigational New Drugs.

    Science.gov (United States)

    1982-09-01

    UNCLASSIFIED N EL MDISPOSITION AND METABOLISM OF INVESTIGATIONAL NEW DRUGS rN4 MRI PROJECT NO. 4266-B FINAL REPORT By Thomas E. Shellenberger September 1982...documents. Ii I DISPOSITION AND METABOLISM OF INVESTIGATIONAL NEW DRUGS [RI PROJECT NO. 4266-B [FINAL REPORT BY Thomas E. Shellenberger September 1982...the Army, Contract No. DAMD-17-76-C-6059, MRI Project No. 4266-B, "Disposition and Metabolism of Investigational New Drugs ." The work was supported by

  3. 77 FR 71802 - Guidance on Investigational New Drug Applications for Positron Emission Tomography Drugs...

    Science.gov (United States)

    2012-12-04

    ... HUMAN SERVICES Food and Drug Administration Guidance on Investigational New Drug Applications for... ``Investigational New Drug Applications for Positron Emission Tomography (PET) Drugs.'' The guidance is intended to assist manufacturers of PET drugs in submitting investigational new drug applications (INDs)....

  4. Preformulation and Formulation of Investigational New Drugs

    Science.gov (United States)

    1999-01-01

    2000 THIS PAGE IS UNCLASSIFIED AD Award Number DAMDl7-92-C-2035 TITLE: Preformulation and Formulation of Investigational New Drugs PRINCIPAL...TITLE AND SUBTITLE 5. FUNDING NUMBERS Preformulation and Formulation of Investigational New Drugs DAMD17-92-C-2035 6. AUTHOR(S) Douglas Flanagan, Ph.D. 7

  5. 76 FR 13880 - Investigational New Drug Applications and Abbreviated New Drug Applications; Technical Amendment

    Science.gov (United States)

    2011-03-15

    ... HUMAN SERVICES Food and Drug Administration 21 CFR Parts 312 and 314 Investigational New Drug Applications and Abbreviated New Drug Applications; Technical Amendment AGENCY: Food and Drug Administration... amending its investigational new drug application (IND) regulations and abbreviated new drug...

  6. 21 CFR 312.7 - Promotion of investigational drugs.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Promotion of investigational drugs. 312.7 Section...) DRUGS FOR HUMAN USE INVESTIGATIONAL NEW DRUG APPLICATION General Provisions § 312.7 Promotion of investigational drugs. (a) Promotion of an investigational new drug. A sponsor or investigator, or any...

  7. What is an Investigational HIV Drug?

    Science.gov (United States)

    ... Children and Adolescents HIV and Women HIV and Gay and Bisexual Men HIV and Older Adults HIV ... vaccines to treat or prevent HIV. In most cases, an investigational drug ... Medical research studies—also called clinical trials—are done to evaluate ...

  8. 76 FR 46303 - Guidance for Industry and Food and Drug Administration Staff: Investigational New Drug...

    Science.gov (United States)

    2011-08-02

    ...: Investigational New Drug Applications for Minimally Manipulated, Unrelated Allogeneic Placental/Umbilical Cord... for Industry and FDA Staff: Investigational New Drug Applications (INDs) for Minimally Manipulated... the availability of a document entitled ``Guidance for Industry and FDA Staff: Investigational...

  9. 77 FR 8262 - Draft Guidance on Investigational New Drug Applications for Positron Emission Tomography Drugs...

    Science.gov (United States)

    2012-02-14

    ... HUMAN SERVICES Food and Drug Administration Draft Guidance on Investigational New Drug Applications for Positron Emission Tomography Drugs; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing the availability of a draft...

  10. Investigational new drugs for focal epilepsy.

    Science.gov (United States)

    Mula, Marco

    2016-01-01

    For more than 30 years, antiepileptic drug development has been based on specific assumptions regarding the neurobiology of epilepsy but all marketed drugs have not changed the proportion of drug refractory patients. It is, therefore, evident that new molecular targets need to be identified. Advances in neurobiology and molecular pharmacology are bringing into the epilepsy field new neurochemical functions such as those modulated by cannabinoid, serotonin, melatonin and galanin receptors. Among all the different compounds, the melatonin type 3 receptor agonist beprodone and cannabidiol are those at the more advanced stage of development. Interestingly, despite the structural analogies with tetrahydrocannabinol, the anticonvulsant activity of cannabidiol is not mediated by an interaction with cannabinoid receptors. Neurosteroids represent another remarkable class of drugs, and among them, ganaxolone is at the most advanced stage of development. Furthermore, for the first time, potential disease-modifying agents and techniques are entering the epilepsy market. Rapalogues such as everolimus and the antibiotic minocycline are currently under development for specific epileptic syndromes like tuberous sclerosis or Angelman syndrome. Finally, optogenetics, though still at an early stage of development, represents a futuristic therapeutic strategy for drug-refractory epilepsy.

  11. Emerging and investigational drugs for premature ejaculation.

    Science.gov (United States)

    McMahon, Chris G

    2016-08-01

    Over the past 20-30 years, the premature ejaculation (PE) treatment paradigm, previously limited to behavioural psychotherapy, has expanded to include drug treatment. Pharmacotherapy for PE predominantly targets the multiple neurotransmitters and receptors involved in the control of ejaculation which include serotonin, dopamine, oxytocin, norepinephrine, gamma amino-butyric acid (GABA) and nitric oxide (NO). The objective of this article is to review emerging PE interventions contemporary data on the treatment of PE was reviewed and critiqued using the principles of evidence-based medicine. Multiple well-controlled evidence-based studies have demonstrated the efficacy and safety of selective serotonin reuptake inhibitors (SSRIs) in delaying ejaculation, confirming their role as first-line agents for the medical treatment of lifelong and acquired PE. Daily dosing of SSRIs is likely to be associated with superior fold increases in IELT compared to on-demand SSRIs. On-demand SSRIs are less effective but may fulfill the treatment goals of many patients. Integrated pharmacotherapy and CBT may achieve superior treatment outcomes in some patients. PDE-5 inhibitors alone or in combination with SSRIs should be limited to men with acquired PE secondary to co-morbid ED. New on-demand rapid acting SSRIs, oxytocin receptor antagonists, or single agents that target multiple receptors may form the foundation of more effective future on-demand medication. Current evidence confirms the efficacy and safety of dapoxetine, off-label SSRI drugs, tramadol and topical anaesthetics drugs. Treatment with α1-adrenoceptor antagonists cannot be recommended until the results of large well-designed RCTs are published in major international peer-reviewed medical journals. As our understanding of the neurochemical control of ejaculation improves, new therapeutic targets and candidate molecules will be identified which may increase our pharmacotherapeutic armamentarium.

  12. Synthetic investigational new drugs for the treatment of tuberculosis.

    Science.gov (United States)

    Kwon, Yong-Soo; Koh, Won-Jung

    2016-01-01

    Tuberculosis (TB) is a major global health concern. And while there are treatments already on the market, there is a demand for new drugs that are effective and safe against Mycobacterium tuberculosis, which reduce the number of drugs and the duration of treatment in both drug-susceptible TB and multidrug-resistant TB (MDR-TB). This review covers promising novel investigational TB drugs that are currently under development. Specifically, the authors review the efficacy of novel agents for the treatment of TB in preclinical, phase I and phase II clinical trials. The authors also review the safety and tolerability profiles of these drugs. Bedaquiline and delamanid are the most promising novel drugs for the treatment of MDR-TB, each having high efficacy and tolerability. However, the best regimen for achieving better outcomes and reducing adverse drug reactions remains to be determined, with safety concerns regarding cardiac events due to QT prolongation still to be addressed. Pretomanid is a novel drug that potentially shortens the duration of treatment in both drug-susceptible and drug-resistant TB in combination with moxifloxacin and pyrazinamide. Linezolid shows marked efficacy in the treatment of MDR-TB and extensively drug-resistant TB (XDR-TB), but the drug is known to cause significant adverse drug reactions, including peripheral neuropathy, optic neuropathy and myelosuppression. These adverse reactions must be considered prior to prescribing long-term usage of this drug.

  13. 78 FR 27116 - Draft Guidance for Industry on Charging for Investigational Drugs Under an Investigational New...

    Science.gov (United States)

    2013-05-09

    ... HUMAN SERVICES Food and Drug Administration 21 CFR Part 312 Draft Guidance for Industry on Charging for... Investigational Drugs Under an IND--Qs & As.'' This guidance is intended to provide information for industry... for industry entitled ``Charging for Investigational Drugs Under an IND--Qs & As.'' In 2009,...

  14. Preformulation and Formulation of Investigational New Drugs

    Science.gov (United States)

    1985-07-01

    WR249,655𔃼CL and WR249,943𔃼C1..; physicochemical characterization of WR238,6O𔃿 investigation of solid-state properties of various lots of WRl71,669...Methocel XD-30018.OO--Hydroxypropylmethylceilulose, US? 2208(100,000 cps) Sodium CMC 7HP --------Sodium carboxymethylcellulose (DS-0.7, high viscosity

  15. Thermoanalytical Investigation of Some Sulfone-Containing Drugs

    OpenAIRE

    2012-01-01

    The thermal behavior of some sulfone-containing drugs, namely, dapsone (DDS), dimethylsulfone (MSM), and topiramate (TOP) in drug substances, and products were investigated using different thermal techniques. These include thermogravimetry (TGA), derivative thermogravimetry (DTG), differential thermal analysis (DTA), and differential scanning calorimetry (DSC). The thermogravimetric data allowed the determination of the kinetic parameters: activation energy (E a ), frequency factor (A), and r...

  16. 21 CFR 312.40 - General requirements for use of an investigational new drug in a clinical investigation.

    Science.gov (United States)

    2010-04-01

    ... new drug in a clinical investigation. 312.40 Section 312.40 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE INVESTIGATIONAL NEW DRUG APPLICATION Administrative Actions § 312.40 General requirements for use of an investigational new drug in...

  17. 21 CFR 312.6 - Labeling of an investigational new drug.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Labeling of an investigational new drug. 312.6... (CONTINUED) DRUGS FOR HUMAN USE INVESTIGATIONAL NEW DRUG APPLICATION General Provisions § 312.6 Labeling of an investigational new drug. (a) The immediate package of an investigational new drug intended...

  18. 75 FR 63189 - Draft Guidance for Industry on Investigational New Drug Applications-Determining Whether Human...

    Science.gov (United States)

    2010-10-14

    ... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry on Investigational New Drug... Drug Administration (FDA) is announcing the availability of a draft guidance for industry entitled... draft guidance for industry entitled ``Investigational New Drug Applications (INDs)--Determining...

  19. An Initial Investigation of the Psychedelic Drug Flashback Phenomena

    Science.gov (United States)

    Matefy, Robert E.; Krall, Roger G.

    1974-01-01

    This study investigated some characteristics of persons experiencing "flashbacks," and provides systematic descriptions of the flashback phenomena. The drug user showed no significant differences in psychopathological characteristics as measured by the MMPI, nor significant differences in attentional processes as measured by the Embedded Figures…

  20. 78 FR 36194 - Draft Guidance for Industry and FDA Staff: Investigational New Drug Applications for Minimally...

    Science.gov (United States)

    2013-06-17

    ... New Drug Applications for Minimally Manipulated, Unrelated Allogeneic Placental/Umbilical Cord Blood... for Industry and FDA Staff: ] Investigational New Drug Applications for Minimally Manipulated... Investigational New Drug Application (IND) for certain hematopoietic progenitor cells from...

  1. 21 CFR 516.125 - Investigational use of minor species new animal drugs to support indexing.

    Science.gov (United States)

    2010-04-01

    ... drugs to support indexing. 516.125 Section 516.125 Food and Drugs FOOD AND DRUG ADMINISTRATION... Species § 516.125 Investigational use of minor species new animal drugs to support indexing. (a) The... Investigational Exemption for a New Animal Drug for Index Listing” and each request for indexing shall be...

  2. [Evaluation of drug cost reduction resulting from the free supply of investigational drugs].

    Science.gov (United States)

    Corvaisier, Stéphane; Ferry, Serge; Rochefort, Françoise

    2003-01-01

    Excluding all other costs or benefits of participation in clinical trials, the objective of this study was to evaluate and analyse the cost avoidance represented by the free supply of the investigational drug in place of paying for a marketed drug. The cost avoided was defined as money that would most likely have been spent, but not because of inclusion of the patient in the clinical study. Only studies for which a marketed alternative drug was available with a standard dosage have been analysed. The numbers of delivered doses or the treatment durations were tabulated from pharmacy dispensing records for each study, and were used to calculate the medication cost avoided. No marketed alternative drug was available for 10 of 56 clinical studies. In total, in 2000, the cost avoidance was estimated between [symbol: see text] 585,492 and [symbol: see text] 603,674, with a wide variability between studies or between patients (CV: 120-520%). The two disease categories associated with the largest cost avoidance were multiple sclerosis and growth hormone deficiency. The cost avoidance was essentially of benefit to the medical insurance or the patient (98%) and was lower than [symbol: see text] 10,000 for the hospital, because 91% of patients are not hospitalised. So, why are clinical studies involving ambulatory patients performed in hospital? Of the 56 studies analysed, 46 could be shown to be non-innovative, because a marketed alternative drug was available. Few studies appeared to permit free access to treatment with non-reimbursable marketed drugs.

  3. Trends in risks associated with new drug development: success rates for investigational drugs.

    Science.gov (United States)

    DiMasi, J A; Feldman, L; Seckler, A; Wilson, A

    2010-03-01

    This study utilizes both public and private data sources to estimate clinical phase transition and clinical approval probabilities for drugs in the development pipelines of the 50 largest pharmaceutical firms (by sales). The study examined the development histories of these investigational compounds from the time point at which they first entered clinical testing (1993-2004) through June 2009. The clinical approval success rate in the United States was 16% for self-originated drugs (originating from the pharmaceutical company itself) during both the 1993-1998 and the 1999-2004 subperiods. For all compounds (including licensed-in and licensed-out drugs in addition to self-originated drugs), the clinical approval success rate for the entire study period was 19%. The estimated clinical approval success rates and phase transition probabilities differed significantly by therapeutic class. The estimated clinical approval success rate for self-originated compounds over the entire study period was 32% for large molecules and 13% for small molecules. The estimated transition probabilities were also higher for all clinical phases with respect to large molecules.

  4. The Economics of Crime: Investigating the Drugs-Crime Channel

    OpenAIRE

    Entorf, Horst; Winker, Peter

    2002-01-01

    The rising trends both in drug addiction and crime rates are of major public concern in Germany. Surprisingly, the economic theory of crime seems to ignore the drugs-crime nexus, whereas the criminological literature considers illicit drug use a main reason of criminal activities. This paper provides an econometric assessment of the drugs-crime channel within a Becker-Ehrlich model of crime supply. We analyse three different channels from drug abuse to crime: system-related, economic-related ...

  5. The Economics of Crime: Investigating the Drugs-Crime Channel

    OpenAIRE

    Entorf, Horst; Winker, Peter

    2002-01-01

    The rising trends both in drug addiction and crime rates are of major public concern in Germany. Surprisingly, the economic theory of crime seems to ignore the drugs-crime nexus, whereas the criminological literature considers illicit drug use a main reason of criminal activities. This paper provides an econometric assessment of the drugs-crime channel within a Becker-Ehrlich model of crime supply. We analyse three different channels from drug abuse to crime: system-related, economic-related ...

  6. Investigating polypharmacy and drug burden index in hospitalised older people.

    Science.gov (United States)

    Best, O; Gnjidic, D; Hilmer, S N; Naganathan, V; McLachlan, A J

    2013-08-01

    To investigate the changes in polypharmacy and the drug burden index (DBI) occurring during hospitalisation for older people. The secondary aim was to examine the associations of these two measures with the length of hospital stay and admission for falls or delirium. A retrospective analysis of patients' medical records was undertaken at a large university teaching hospital (Sydney, Australia) for patients with the age of ≥ 65 years and admitted under the care of the geriatric medicine or rehabilitation teams. Polypharmacy was defined as the use of more than five regular medications. The DBI measures exposure to drugs with anticholinergic and sedative effects. Logistic regression analysis was conducted to investigate the associations between polypharmacy and DBI with outcome measures. Data are presented using odds ratios with 95% confidence intervals. A total of 329 patients was included in this study. The mean (± standard deviation) age of the population was 84.6 ± 7.0 years, 62% were female and 40% were admitted from residential aged-care facilities. On admission, polypharmacy was observed in 60% of the cohort and DBI exposure for 50%. DBI and polypharmacy exposure decreased during hospitalisation, but only the number of medications taken decreased by a statistically significant margin (P = 0.02). Patients with a high DBI (≥ 1) were approximately three times more likely to be admitted for delirium than those with no DBI exposure (odds ratio, 2.95; 95% confidence interval, 1.34-6.51). In the present study, DBI was associated with an increased risk of hospital admission for delirium only. Polypharmacy was not associated with any of the clinical measures. © 2013 The Authors; Internal Medicine Journal © 2013 Royal Australasian College of Physicians.

  7. 75 FR 59935 - Investigational New Drug Safety Reporting Requirements for Human Drug and Biological Products and...

    Science.gov (United States)

    2010-09-29

    ... and Research (CDER)-related information are posted on the Internet at http://www.fda.gov/Drugs... that do not result in hospitalization, or the development of drug dependency or drug abuse.'' (Comment...

  8. INVESTIGATION ON EFFECT OF DRUG DOSING REGIMENTS ON DRUG DELIVERY IN SOLID TUMOR VIA LUMPED PARAMETER MODELING AND ANIMAL EXPERIMENTS

    Institute of Scientific and Technical Information of China (English)

    GAO Ci-xiu; XU Shi-xiong; JIANG Yu-ping; TU Jiang-long

    2009-01-01

    This work aims to investigate the effects of dosing regiments on drug delivery in solid tumors and to validate them with experiments on rats.The lumped parameter models of pharmacokinetics and of drug delivery in tumor were developed to simulate time courses of average drug concentration(Ct)of tumor interstitium in two types of dosing regiments(i.e.,single-shot and triple-shot ones).The two regiments were performed via antitumor drug,hydroxycamptothecin(HCPT),on rats,to measure the drug concentration in the tumor.The simulations of the drug concentration in the tumor of the two dosing regiments were conducted and compared with the experimental data on rats.The coefficients in the models were investigated.It is concluded that the triple-shot method is more effective than that of single-shot injection.The present lumped-parameter model is quantitatively competent for drug delivery in solid tumor.

  9. Drugs Used in Sexual Assaults: Features and Toxicological Investigations

    Directory of Open Access Journals (Sweden)

    Pinar Efeoglu

    2013-06-01

    Full Text Available Drugs used in sexual assault, which are also called as date rape drugs, are common phenomenon of crime in many countries. In a typical scenario, a perpetrator adds a date-rape drug which has sedative effect into alcoholic or non-alcoholic beverage of an unsuspecting person. After drug administration, mostly amnesia and symptoms such as confussion, loss of memory, lack of muscle control, dizziness occur. The main drugs in sexual assaults are benzodiazepines such as γ-hydroxy butyrate and its analogs, clonazepam, alprazolam, flunitrazepam, oxazepam, ketamine, barbiturates, antidepressants, cocaine and stimulants. Most of these drugs are colorless, odorless and highly soluble in alcohol or other beverages quickly. They are rapidly absorbed and eliminated after oral administration. A victim may complain to police or other legal forces after several days due to emotional trauma as shame, fear, doubt and disbelief. For this reason, It is important to know what time the sample is taken from the victim to confirm the presence of the drug. In this study, we will present a general approach to date-rape drugs used in sexual assault. [Archives Medical Review Journal 2013; 22(3.000: 418-425

  10. Will the International Criminal Court Investigate Mexico's "Drug War"?

    OpenAIRE

    Pérez Caballero, Jesús

    2014-01-01

    The violence of Mexico's so-called "war on drugs" has caught the attention of the international community, with calls for the International Criminal Court (ICC) to turn its attention to the country. If they're successful, high-level government officials - or even leaders of drug trafficking organizations - may be prosecuted in the Hague. But it's a difficult road ahead.

  11. INVESTIGATING DRUG-USE IN PREGNANCY - METHODOLOGICAL PROBLEMS AND PERSPECTIVES

    NARCIS (Netherlands)

    DEJONGVANDENBERG, LTW; VANDENBERG, PB; HAAIJER-RUSKAMP, FM; DUKES, MNG; WESSELING, H

    1991-01-01

    In this study the use of prescribed drugs before, during and after pregnancy is described. The study is based on data obtained from pharmacy records of 1,948 women who delivered a live-born infant. Different measures to evaluate drug exposure are used. During the nine months of pregnancy 86% of the

  12. 78 FR 42965 - Guidance for Industry: Enforcement Policy Regarding Investigational New Drug Requirements for Use...

    Science.gov (United States)

    2013-07-18

    ... Investigational New Drug Requirements for Use of Fecal Microbiota for Transplantation To Treat Clostridium... new drug (IND) requirements for the use of fecal microbiota for transplantation (FMT) to treat...

  13. An investigation into keratinolytic enzymes to enhance ungual drug delivery.

    Science.gov (United States)

    Mohorcic, M; Torkar, A; Friedrich, J; Kristl, J; Murdan, S

    2007-03-06

    The topical therapy of nail diseases is limited by the low permeability of drugs through the nail plate. To increase drug penetration, the integrity of the nail plate must be compromised to a certain extent. We hypothesised that keratinolytic enzymes might decrease the barrier properties of the nail plate by hydrolysing the nail keratins, and thereby enhance ungual drug permeation. To determine enzyme action on nail plates, nail clippings were incubated at 35 degrees C, in the presence of keratinase at optimal pH for 48h, after which the nail plates were examined using scanning electron microscopy. It was found that the enzyme acted on the intercellular matrix which holds nail cells together, such that corneocytes on the dorsal surface separated from one another and 'lifted off' the nail plate. In addition, the surface of the corneocytes was corroded. Permeation studies using modified Franz diffusion cells and bovine hoof membranes as a model for the nail plate showed that the enzyme enhanced drug permeation through the hoof membrane. The permeability and partition coefficients, and the drug flux were found to be significantly increased in the presence of the enzyme. We can conclude that the enzyme, via its hydrolytic action on nail plate proteins, could increase ungual drug delivery.

  14. Investigation of Physicochemical Drug Properties to Prepare Fine Globular Granules Composed of Only Drug Substance in Fluidized Bed Rotor Granulation.

    Science.gov (United States)

    Mise, Ryohei; Iwao, Yasunori; Kimura, Shin-Ichiro; Osugi, Yukiko; Noguchi, Shuji; Itai, Shigeru

    2015-01-01

    The effect of some drug properties (wettability and particle size distribution) on granule properties (mean particle size, particle size distribution, sphericity, and granule strength) were investigated in a high (>97%) drug-loading formulation using fluidized bed rotor granulation. Three drugs: acetaminophen (APAP); ibuprofen (IBU); and ethenzamide (ETZ) were used as model drugs based on their differences in wettability and particle size distribution. Granules with mean particle sizes of 100-200 µm and a narrow particle size distribution (PSD) could be prepared regardless of the drug used. IBU and ETZ granules showed a higher sphericity than APAP granules, while APAP and ETZ granules exhibited higher granule strength than IBU. The relationship between drug and granule properties suggested that the wettability and the PSD of the drugs were critical parameters affecting sphericity and granule strength, respectively. Furthermore, the dissolution profiles of granules prepared with poorly water-soluble drugs (IBU and ETZ) showed a rapid release (80% release in 20 min) because of the improved wettability with granulation. The present study demonstrated for the first time that fluidized bed rotor granulation can prepare high drug-loaded (>97%) globular granules with a mean particle size of less than 200 µm and the relationship between physicochemical drug properties and the properties of the granules obtained could be readily determined, indicating the potential for further application of this methodology to various drugs.

  15. 78 FR 13070 - Guidance for Clinical Investigators, Industry, and Food and Drug Administration Staff: Financial...

    Science.gov (United States)

    2013-02-26

    ..., Industry, and Food and Drug Administration Staff: Financial Disclosure by Clinical Investigators..., Industry, and FDA Staff: Financial Disclosure by Clinical Investigators.'' This guidance is intended to... governing financial disclosure by clinical investigators. This guidance provides FDA's responses to the...

  16. 21 CFR 320.31 - Applicability of requirements regarding an “Investigational New Drug Application.”

    Science.gov (United States)

    2010-04-01

    ...Investigational New Drug Application.â 320.31 Section 320.31 Food and Drugs FOOD AND DRUG ADMINISTRATION... Applicability of requirements regarding an “Investigational New Drug Application.” (a) Any person planning to... drug product that is the subject of an approved new drug application or abbreviated new...

  17. Tailored beads made of dissolved cellulose - Investigation of their drug release properties

    DEFF Research Database (Denmark)

    Yildir, Emrah; Kolakovic, Ruzica; Genina, Natalja;

    2013-01-01

    In the frame of this work, we have investigated drug entrapping and release abilities of new type of porous cellulose beads (CBs) as a spherical matrix system for drug delivery. For that purpose, CBs prepared with three different methods were used as drug carriers and three compounds, anhydrous...... efficacy. Also, the drug release rates were controlled by solubility of model drugs (diffusion controlled release). In conclusion, CBs from dissolved cellulose show promise in achieving controlled drug delivery. © 2013 Elsevier B.V. All rights reserved....

  18. Theoretical and experimental investigation of drug-polymer interaction and miscibility and its impact on drug supersaturation in aqueous medium.

    Science.gov (United States)

    Baghel, Shrawan; Cathcart, Helen; O'Reilly, Niall J

    2016-10-01

    Amorphous solid dispersions (ASDs) have the potential to offer higher apparent solubility and bioavailability of BCS class II drugs. Knowledge of the solid state drug-polymer solubility/miscibility and their mutual interaction are fundamental requirements for the effective design and development of such systems. To this end, we have carried out a comprehensive investigation of various ASD systems of dipyridamole and cinnarizine in polyvinylpyrrolidone (PVP) and polyacrylic acid (PAA) at different drug loadings. Theoretical and experimental examinations (by implementing binary and ternary Flory-Huggins (F-H) theory) related to drug-polymer interaction/miscibility including solubility parameter approach, melting point depression method, phase diagram, drug-polymer interaction in the presence of moisture and the effect of drug loading on interaction parameter were performed. The information obtained from this study was used to predict the stability of ASDs at different drug loadings and under different thermal and moisture conditions. Thermal and moisture sorption analysis not only provided the composition-dependent interaction parameter but also predicted the composition dependent miscibility. DPM-PVP, DPM-PAA and CNZ-PAA systems have shown molecular level mixing over the complete range of drug loading. For CNZ-PVP, the presence of a single Tg at lower drug loadings (10, 20 and 35%w/w) indicates the formation of solid solution. However, drug recrystallization was observed for samples with higher drug weight fractions (50 and 65%w/w). Finally, the role of polymer in maintaining drug supersaturation has also been explored. It has been found that drug-polymer combinations capable of hydrogen-bonding in the solution state (DPM-PVP, DPM-PAA and CNZ-PAA) are more effective in preventing drug crystallization compared to the drug-polymer systems without such interaction (CNZ-PVP). The DPM-PAA system outperformed all other ASDs in various stability conditions (dry-state, in

  19. Methodologies for investigating drug metabolism at the early drug discovery stage: prediction of hepatic drug clearance and P450 contribution.

    Science.gov (United States)

    Emoto, Chie; Murayama, Norie; Rostami-Hodjegan, Amin; Yamazaki, Hiroshi

    2010-10-01

    The attrition rate in drug development is being reduced by continuous advances in science and technology introduced by various academic institutions and pharmaceutical companies. This has been certainly noticeable in reducing the frequency with which unfavorable absorption, distribution, metabolism, and elimination (ADME) characteristics of any candidate drug causes failure in clinical development. Nonetheless, it is important that the objectives in reducing attrition during later stages of development are matched by information generated in the earliest stage of discovery. In this review, we summarize the methodologies employed during the early stages of drug discovery and discuss new findings in the areas of (1) drug metabolism enzymes, (2) the contribution of cytochrome P450 enzymes (P450, CYP) to hepatic metabolism, (3) prediction of hepatic intrinsic clearance, (4) reaction phenotyping, and (5) the metabolic differences between highly homologous enzymes such as CYP3A4 and CYP3A5. The total contribution of P450 and UDP-glucuronosyltransferases to drug metabolism is reported to be more than 80%; therefore, glucuronidation is increasingly recognized as an important clearance pathway in addition to that of P450 enzymes. When estimating the contribution of P450, interpreting the results of inhibition studies using a single P450 inhibitor can lead to false conclusions. For instance, 1-aminobenzotriazole and SKF-525A have a varying range of IC(50) values for inhibition of drug exidation-reaction by different CYP450 enzymes. There are disparities between methodologies at early stage drug discovery and late stage development. For example, although the drug depletion approach for the prediction of hepatic intrinsic clearance may not be desirable at late stages of development, it is suitable at the early drug discovery stage since kinetic characterization and measurement of specific drug metabolites are not required. Data from protein binding assays in plasma and

  20. Investigation of Frequency of Leftover Drugs at Home and Related Factors

    Directory of Open Access Journals (Sweden)

    Muharrem Ucar

    2009-04-01

    Full Text Available AIM: The purpose of this survey was to investigate the frequency of leftover drugs at homes and related factors regarding this problem. METHOD: This descriptive study was performed among 692 non-medical personnel servicing at two military bases in December 2006. Data were collected by using a questionnaire, which had been developed by the investigators. Frequencies and percents were used as descriptive statistics. Chi-square test was used to compare the frequencies of leftover drugs according to certain variables. RESULTS: Of the total participants 78,8% were males, 72,8% aged between 18 to 39, and 29,6% were unmarried. The findings revealed that 61,3% of the participants had leftover drugs at their homes. Participants living with together 2 to 4 family members had higher frequencies of leftover drugs at homes. When we looked at the frequencies of leftover drugs according to drug use behaviors; the frequency of leftover drug was determined higher among those who stated; the recipe was not explained sufficiently, he did not use drugs as directed, he kept drugs until due time when did not use all of the drugs, he kept drugs in a box or bag, he visited a health center in order to have a recipe (p<0,05. CONCLUSION: It was determined leftover drugs were kept at nearly two third of the participants’ homes. Regarding incompleteness of treatment, the intoxication risk for children, and drug waste, this frequency of drug leftover was high, and all responsible professions in the chain of rationale drug use particularly physicians should be awaked on this issue. The use of drugs in a recipe should be explained to patients clearly. [TAF Prev Med Bull 2009; 8(2.000: 113-118

  1. 21 CFR 601.50 - Confidentiality of data and information in an investigational new drug notice for a biological...

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Confidentiality of data and information in an investigational new drug notice for a biological product. 601.50 Section 601.50 Food and Drugs FOOD AND DRUG... Information § 601.50 Confidentiality of data and information in an investigational new drug notice for...

  2. [Therapeutic uses of investigational drugs: research extension, compassionate use, and expanded access].

    Science.gov (United States)

    Goldim, José Roberto

    2008-03-01

    This article describes the methodological, regulatory, and ethical aspects of the different therapeutic uses of investigational drugs--research extension, compassionate use, and expanded access. Worldwide, the principle challenges of this kind of treatment are: setting minimum quality standards for researchers, as well as institutions, so that projects can include drugs at various stages of development; training of evaluation and assessment committees on the methodological, regulatory, and ethical aspects of new drug research; clearly outlining the relationship between researchers and funding organizations and between researchers and study participants; and understanding the opposition to the recent proposal to enable drug manufacturers to charge for drugs used in research studies.

  3. Numerical investigation of pulmonary drug delivery under mechanical ventilation conditions

    Science.gov (United States)

    Banerjee, Arindam; van Rhein, Timothy

    2012-11-01

    The effects of mechanical ventilation waveform on fluid flow and particle deposition were studied in a computer model of the human airways. The frequency with which aerosolized drugs are delivered to mechanically ventilated patients demonstrates the importance of understanding the effects of ventilation parameters. This study focuses specifically on the effects of mechanical ventilation waveforms using a computer model of the airways of patient undergoing mechanical ventilation treatment from the endotracheal tube to generation G7. Waveforms were modeled as those commonly used by commercial mechanical ventilators. Turbulence was modeled with LES. User defined particle force models were used to model the drag force with the Cunningham correction factor, the Saffman lift force, and Brownian motion force. The endotracheal tube (ETT) was found to be an important geometric feature, causing a fluid jet towards the right main bronchus, increased turbulence, and a recirculation zone in the right main bronchus. In addition to the enhanced deposition seen at the carinas of the airway bifurcations, enhanced deposition was also seen in the right main bronchus due to impaction and turbulent dispersion resulting from the fluid structures created by the ETT. Authors acknowledge financial support through University of Missouri Research Board Award.

  4. [Contributions of SGLT-2 and new drugs under investigation].

    Science.gov (United States)

    Mediavilla Bravo, J J

    2014-07-01

    DeFronzo spoke of the "ominous octet", in which he referred to the existence of distinct pathways and organs related to the physiopathology of type 2 diabetes mellitus (DM2). One of these key organs is the kidney, which plays an important role in regulating glucose metabolism through gluconeogenesis and through glomerular filtration and glucose reabsorption in the proximal convoluted tubules. Approximately 180 g of glucose are filtered to the renal tubule from the blood stream through the glomerulus. The filtrate is subsequently reabsorbed from the tubules to the peritubular capillaries through the action of sodium glucose cotransporters (SGLT). There are 2 main cotransporters in the kidney, SGLT1 and SGLT2, which reabsorb the glucose (10% and 90%, respectively) and return it to the blood. In persons with DM2, SGLT2 is increased, leading to greater renal absorption of glucose, which has adverse effects as it contributes to the maintenance of hyperglycemia. Selective pharmacological SGLT2 inhibition increases renal glucose excretion and secondarily reduces its plasma values. SGLT2 inhibitors act exclusively on the kidney, reduce glycosylated hemoglobin (HbA1c) by about 0.66%, decrease blood pressure, and induce a weight loss of approximately 1.8 kg. These drugs have a low risk of hypoglycemia but carry an increased risk of genitourinary infections. Several clinical trials have shown that dapagliflozin (10mg/day), the first SGLT2 inhibitor commercialized in Spain, produces a statistically significant reduction in HbA1c of 0.82-0.97%, both in monotherapy and in combination with metformin, glimepiride, pioglitazone, or insulin. Its use produces a weight loss of between 2 and 3 kg and reduces both systolic and diastolic blood pressure, while the risk of hypoglycemias is low.

  5. General issues and precautions in the design for clinical trials of investigational new drugs.

    Science.gov (United States)

    Hu, Liang-ping; Bao, Xiao-lei

    2011-02-01

    The general problems existing in the clinical trials of investigational new drugs involve some key aspects such as the guiding principles, research designs, quality controls and statistical analyses. This paper explores the eight general issues in the clinical trials of investigational new drugs and presents precautionary measures with high operability. Research on the clinical trials of investigational new drugs is a complex project, which should be carried out strictly according to the policies, laws, criteria and operating rules set by related agencies. The neglect of research designs and data analyses will lead clinical trials to failure.

  6. Targeting the subtypes of breast cancer: rethinking investigational drugs.

    Science.gov (United States)

    Curigliano, Giuseppe; Locatelli, Marzia; Fumagalli, Luca; Brollo, Janaina; Munzone, Elisabetta; Nolé, Franco; Criscitiello, Carmen; Goldhirsch, Aron

    2012-02-01

    The choice of adjuvant treatments for women with breast cancer is based on several features that take into account the heterogeneity of the disease. Questions raised during the decision process include the following: i) What leads to the use of endocrine therapy? ii) What leads to the use of anti-HER2 therapy? iii) What justifies the use of chemotherapy? Choices of adjuvant treatment are based on parameters defined by molecular characterization of breast cancer subtypes or by approximations to this classification using traditional clinical-pathological features. Clinicians should consider cases within the various distinct subpopulation in order to properly select the most 'personalized' adjuvant therapeutic approach. Sensitivity to chemotherapy and/or targeted agents in subtypes of breast cancers are predictable based on gene pathway alterations and associated gene products. This review covers several clinical data on several investigational agents for early-stage breast cancer molecular subtypes. We selected from literature data prospective Phase I, II and III clinical trials of chemotherapy (weekly or daily schedules), including indicators of activity and toxicity and data on survival/mortality. The future of many investigational therapeutics in breast cancer is linked to our ability to identify the most druggable target in each subtype.

  7. Stakeholders' views on the ethical challenges of pragmatic trials investigating pharmaceutical drugs

    NARCIS (Netherlands)

    Kalkman, S; van Thiel, Ghislaine J M W; Grobbee, Diederick E.; Meinecke, Anna Katharina; Zuidgeest, Mira G P; van Delden, Johannes J M

    2016-01-01

    Background: We explored the views of key stakeholders to identify the ethical challenges of pragmatic trials investigating pharmaceutical drugs. A secondary aim was to capture stakeholders' attitudes towards the implementation of pragmatic trials in the drug development process. Methods: We conducte

  8. Denosumab: an investigational drug for the management of postmenopausal osteoporosis

    Directory of Open Access Journals (Sweden)

    E Michael Lewiecki

    2008-08-01

    Full Text Available E Michael LewieckiNew Mexico Clinical Research & Osteoporosis Center, Albuquerque, New Mexico, USAAbstract: Denosumab (AMG 162 is an investigational fully human monoclonal antibody with a high affinity and specificity for receptor activator of nuclear factor-κB ligand (RANKL, a cytokine member of the tumor necrosis factor family. RANKL, the principal mediator of osteoclastic bone resorption, plays a major role in the pathogenesis of postmenopausal osteoporosis and other skeletal disorders associated with bone loss. Denosumab inhibits the action of RANKL, thereby reducing the differentiation, activity, and survival of osteoclasts, and lowering the rate of bone resorption. Clinical trials have shown that denosumab increases bone mineral density (BMD and reduces bone turnover in postmenopausal women with low BMD. Studies to evaluate the fracture risk benefit and long-term safety of denosumab in women with postmenopausal osteoporosis (PMO are ongoing. Denosumab is a potential treatment for PMO and other skeletal disorders.Keywords: osteoporosis, treatment, denosumab, AMG 162, RANKL, OPG

  9. An investigation of classification algorithms for predicting HIV drug resistance without genotype resistance testing

    CSIR Research Space (South Africa)

    Brandt, P

    2014-01-01

    Full Text Available is limited in low-resource settings. In this paper we investigate machine learning techniques for drug resistance prediction from routine treatment and laboratory data to help clinicians select patients for confirmatory genotype testing. The techniques...

  10. 21 CFR 514.12 - Confidentiality of data and information in an investigational new animal drug notice.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Confidentiality of data and information in an investigational new animal drug notice. 514.12 Section 514.12 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS NEW ANIMAL...

  11. Glass Forming Ability of Amorphous Drugs Investigated by Continuous Cooling and Isothermal Transformation.

    Science.gov (United States)

    Blaabjerg, Lasse I; Lindenberg, Eleanor; Löbmann, Korbinian; Grohganz, Holger; Rades, Thomas

    2016-09-06

    The aim of this study was to investigate the glass forming ability of 12 different drugs by the determination of continuous cooling and isothermal transformation diagrams in order to elucidate if an inherent differentiation between the drugs with respect to their the glass forming ability can be made. Continuous-cooling-transformation (CCT) and time-temperature-transformation (TTT) diagrams of the drugs were developed in order to predict the critical cooling rate necessary to convert the drug from the melt into an amorphous form. While TTT diagrams overestimated the actual critical cooling rate, they allowed an inherent differentiation of glass forming ability for the investigated drugs into drugs that are extremely difficult to amorphize (>750 °C/min), drugs that require modest cooling rates (>10 °C/min), and drugs that can be made amorphous even at very slow cooling rates (>2 °C/min). Thus, the glass forming ability can be predicted by the use of TTT diagrams. In contrast to TTT diagrams, CCT diagrams may not be suitable for small organic molecules due to poor separation of exothermic events, which makes it difficult to determine the zone of recrystallization. In conclusion, this study shows that glass forming ability of drugs can be predicted by TTT diagrams.

  12. 21 CFR 312.160 - Drugs for investigational use in laboratory research animals or in vitro tests.

    Science.gov (United States)

    2010-04-01

    ... research animals or in vitro tests. 312.160 Section 312.160 Food and Drugs FOOD AND DRUG ADMINISTRATION... Drugs for Investigational Use in Laboratory Research Animals or In Vitro Tests § 312.160 Drugs for investigational use in laboratory research animals or in vitro tests. (a) Authorization to ship. (1)(i) A...

  13. [Results of a drug use investigation of nanoparticle albumin-bound Paclitaxel for breast cancer].

    Science.gov (United States)

    Nakamura, Seigo; Iwata, Hiroji; Funato, Yuya; Ito, Kunio; Ito, Yoshinori

    2015-04-01

    A drug use investigation of nanoparticle albumin-bound paclitaxel was conducted based on conditions for approval. A total of 963 patients were enrolled in this study from September 24, 2010 to February 14, 2011. Twenty-nine patients were excluded, and a total of 934 patients were evaluated for determining the safety of nanoparticle albumin-bound paclitaxel. Adverse drug reactions were observed in 92.8%of the patients, and major adverse drug reactions included myelosuppression and peripheral sensory neuropathy, both of which are characteristic adverse reactions of paclitaxel treatment. Both adverse drug reactions were observed at a high frequency after the second course of treatment, resulting in these reactions being primary causes for discontinuation. Increase in the rates of continuous drug administration may be accomplished by carrying out laboratory tests and noting the medical history in order to prevent myelosuppression from becoming serious and to perform earlier countermeasures for peripheral sensory neuropathy, leading to improved therapeutic effects.

  14. 21 CFR 511.1 - New animal drugs for investigational use exempt from section 512(a) of the act.

    Science.gov (United States)

    2010-04-01

    ... investigational animals in clinical trials. Not for use in humans. Edible products of investigational animals are... 21 Food and Drugs 6 2010-04-01 2010-04-01 false New animal drugs for investigational use exempt..., DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS NEW...

  15. Benchmarking human protein complexes to investigate drug-related systems and evaluate predicted protein complexes.

    Directory of Open Access Journals (Sweden)

    Min Wu

    Full Text Available Protein complexes are key entities to perform cellular functions. Human diseases are also revealed to associate with some specific human protein complexes. In fact, human protein complexes are widely used for protein function annotation, inference of human protein interactome, disease gene prediction, and so on. Therefore, it is highly desired to build an up-to-date catalogue of human complexes to support the research in these applications. Protein complexes from different databases are as expected to be highly redundant. In this paper, we designed a set of concise operations to compile these redundant human complexes and built a comprehensive catalogue called CHPC2012 (Catalogue of Human Protein Complexes. CHPC2012 achieves a higher coverage for proteins and protein complexes than those individual databases. It is also verified to be a set of complexes with high quality as its co-complex protein associations have a high overlap with protein-protein interactions (PPI in various existing PPI databases. We demonstrated two distinct applications of CHPC2012, that is, investigating the relationship between protein complexes and drug-related systems and evaluating the quality of predicted protein complexes. In particular, CHPC2012 provides more insights into drug development. For instance, proteins involved in multiple complexes (the overlapping proteins are potential drug targets; the drug-complex network is utilized to investigate multi-target drugs and drug-drug interactions; and the disease-specific complex-drug networks will provide new clues for drug repositioning. With this up-to-date reference set of human protein complexes, we believe that the CHPC2012 catalogue is able to enhance the studies for protein interactions, protein functions, human diseases, drugs, and related fields of research. CHPC2012 complexes can be downloaded from http://www1.i2r.a-star.edu.sg/xlli/CHPC2012/CHPC2012.htm.

  16. Recent Advances in chemistry and pharmacology of 2-methoxyestradiol: An anticancer investigational drug.

    Science.gov (United States)

    Kumar, B Sathish; Raghuvanshi, Dushyant Singh; Hasanain, Mohammad; Alam, Sarfaraz; Sarkar, Jayanta; Mitra, Kalyan; Khan, Feroz; Negi, Arvind S

    2016-06-01

    2-Methoxyestradiol (2ME2), an estrogen hormone metabolite is a potential cancer chemotherapeutic agent. Presently, it is an investigational drug under various phases of clinical trials alone or in combination therapy. Its anticancer activity has been attributed to its antitubulin, antiangiogenic, pro-apoptotic and ROS induction properties. This anticancer drug candidate has been explored extensively in last twenty years for its detailed chemistry and pharmacology. Present review is an update of its chemistry and biological activity. It also extends an assessment of potential of 2ME2 and its analogues as possible anticancer drug in future. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Investigation of Drug Release from PEO Tablet Matrices in the Presence of Vitamin E as Antioxidant.

    Science.gov (United States)

    Shojaee, Saeed; Nokhodchi, Ali; Cumming, Iain; Alhalaweh, Amjad; Kaialy, Waseem

    2015-01-01

    The objective of this study was to investigate the influence of drug type on the release of drug from PEO matrix tablets accompanied with the impact of vitamin E succinate as antioxidant. The result showed that the presence of vitamin E promoted a stable release rate of soluble drug propranolol HCl from aged PEO matrix tablets, which was similar to fresh sample, regardless of molecular weight (MW) of PEO. However, the influence of the presence of vitamin E on the release rate of partially soluble drug, theophylline, was dependent on the MW of PEO; i.e., fast and unstable drug release was obtained in the case of low MW PEO 750 whereas stable drug release was obtained in the case of high MW PEO 303. The release of low water-soluble drug zonisamide was stable regardless of both the presence of vitamin E and the MW of PEO. The presence of vitamin E slightly slowed the release of zonisamide from aged PEO 303 matrices but not PEO 750 matrices. Therefore, in order to achieve a suitable controlled release profile from PEO matrices, not only the presence of vitamin E but also the solubility of the drug and the MW of polyox should be considered.

  18. Investigation of parameters highlighting drug induced small changes of the T-wave's morphology for drug safety studies.

    Science.gov (United States)

    Baas, Tobias; Gräfe, Ksenija; Khawaja, Antoun; Dössel, Olaf

    2011-01-01

    In guideline E14, the American Food and Drug Administration (FDA) requests for clinical studies to investigate the prolongation of the heart rate corrected QT-interval (QTc) of the ECG. As drug induced QT-prolongation can be caused by changes in the repolarisation of the ventricles, it is so far a thorough ECG biomarker of risk for ventricular tachyarrhythmias and Torsade de Pointes (TdP). Ventricular repolarisation changes not only change QT but also influence the morphology of the T-wave. In a (400 mg single dose) Moxifloxacin positive control study both, QTc and several descriptors describing the T-wave morphology have been measured. Moxifloxacin is changing two shape dependent descriptors significantly (P<0.05) about 3 to 4 hours after a 400 mg oral single dose of Moxifloxacin.

  19. Guidance on preparing an investigational new drug application for fecal microbiota transplantation studies.

    Science.gov (United States)

    Kelly, Colleen R; Kunde, Sachin S; Khoruts, Alexander

    2014-02-01

    Fecal microbiota transplantation (FMT) is an effective treatment for Clostridium difficile infections that are refractory to antibiotic therapy. Because of the important roles of the microbiota in the function of the gastrointestinal tract and other aspects of human physiology, there is a growing interest in studying FMT for other clinical indications. The US Food and Drug Administration regulates clinical studies to evaluate the safety and efficacy of FMT. Studies of FMT for recurrent Clostridium difficile infection or other indications could require submission of an investigational new drug application. Most academic physicians and investigators do not have the regulatory experience necessary to undertake this process. We provide guidance to researchers on the preparation and submission of investigational new drug applications to study FMT. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

  20. Investigation of Diffusion Characteristics through Microfluidic Channels for Passive Drug Delivery Applications

    Directory of Open Access Journals (Sweden)

    Marcus J. Goudie

    2016-01-01

    Full Text Available Microfluidics has many drug delivery applications due to the ability to easily create complex device designs with feature sizes reaching down to the 10s of microns. In this work, three different microchannel designs for an implantable device are investigated for treatment of ocular diseases such as glaucoma, age-related macular degeneration (AMD, and diabetic retinopathy. Devices were fabricated using polydimethylsiloxane (PDMS and soft lithography techniques, where surface chemistry of the channels was altered using 2-[methoxy(polyethyleneoxypropyl]trimethoxysilane (PEG-silane. An estimated delivery rate for a number of common drugs was approximated for each device through the ratio of the diffusion coefficients for the dye and the respective drug. The delivery rate of the model drugs was maintained at a physiological condition and the effects of channel design and surface chemistry on the delivery rate of the model drugs were recorded over a two-week period. Results showed that the surface chemistry of the device had no significant effect on the delivery rate of the model drugs. All designs were successful in delivering a constant daily dose for each model drug.

  1. Investigation of Diffusion Characteristics through Microfluidic Channels for Passive Drug Delivery Applications.

    Science.gov (United States)

    Goudie, Marcus J; Ghuman, Alyssa P; Collins, Stephanie B; Pidaparti, Ramana M; Handa, Hitesh

    2016-01-01

    Microfluidics has many drug delivery applications due to the ability to easily create complex device designs with feature sizes reaching down to the 10s of microns. In this work, three different microchannel designs for an implantable device are investigated for treatment of ocular diseases such as glaucoma, age-related macular degeneration (AMD), and diabetic retinopathy. Devices were fabricated using polydimethylsiloxane (PDMS) and soft lithography techniques, where surface chemistry of the channels was altered using 2-[methoxy(polyethyleneoxy)propyl]trimethoxysilane (PEG-silane). An estimated delivery rate for a number of common drugs was approximated for each device through the ratio of the diffusion coefficients for the dye and the respective drug. The delivery rate of the model drugs was maintained at a physiological condition and the effects of channel design and surface chemistry on the delivery rate of the model drugs were recorded over a two-week period. Results showed that the surface chemistry of the device had no significant effect on the delivery rate of the model drugs. All designs were successful in delivering a constant daily dose for each model drug.

  2. Investigation of interaction between the drug and cell membrane by capillary electrophoresis

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    By introducing cell membrane into electrophoretic buffer as pseudo-stationary phase,a novel capillary electrophoresis method was established to explore the interaction between drugs and cell membrane,where the interaction between citalopram and rabbit red blood cell membrane was used as an example. A series of concentrations of cell membrane were suspended into the running buffer by peak-shift method. The binding constant of citalopram to rabbit red blood cell membrane of 0.977 g-1·L was obtained after treatment of Scatchard plot. This method could provide not only a new way for the investigation on the interactions between drugs and cell membrane,but also a new approach for high throughput screening of the drug membrane permeability,biological activity,and evaluating drugs in vivo.

  3. Investigation of Physicochemical Drug Properties to Prepare Fine Globular Granules Composed of Only Drug Substance in Fluidized Bed Rotor Granulation

    National Research Council Canada - National Science Library

    Mise, Ryohei; Iwao, Yasunori; Kimura, Shin-ichiro; Osugi, Yukiko; Noguchi, Shuji; Itai, Shigeru

    2015-01-01

    ...%) drug-loading formulation using fluidized bed rotor granulation. Three drugs: acetaminophen (APAP); ibuprofen (IBU); and ethenzamide (ETZ) were used as model drugs based on their differences in wettability and particle size distribution...

  4. Investigation and Optimization of the Effect of Polymers on Drug Release of Norfloxacin from Floating Tablets.

    Science.gov (United States)

    Gadade, Dipak D; Sarda, Kalpana; Shahi, Sadhana R

    2016-01-01

    Norfloxacin is fluoroquinolone anti-infective used in the treatment of urinary tract infections, prostatitis, gonorrhea and genital tract infections. It has plasma half life of 3 to 4 h requiring multiple dosing in the treatment. Releaseretarding polymers can be used to modulate the drug release of norfloxacin. The objective of this study was to investigate the effect of release-retarding polymers on the drug release of norfloxacin from floating tablets. Norfloxacin was procured as a gift sample from Concept Pharma Ltd. Aurangabad (India) and HPMC K100M was procured as a gift sample from Colorcon Asia Pvt. Ltd., Goa (India). The tablets were prepared by direct compression method and various pharmaceutical parameters were evaluated. It was observed that all tablet formulations F1-F9 retained the drug release up to 12 h with good floating property but only Batch-F4 complies with the USP dissolution limits with a minimum floating lag time. The drug release kinetics were evaluated by the model-dependent (curve fitting) method using PCP Disso v3 software shows Batch-F4 shows to best fit with Peppas model for which R2 value was 0.9921 and the release exponent value was 0.6892. The drug release kinetics study indicates that the floating tablets release the drug by diffusion followed by erosion mechanism. Obtained in-vitro drug release data was analyzed by design expert software for drug release at first hour and at 12th h values and found that release the selected independent variables like HPMC K100M and sodium alginate concentration has a significant effect on drug release.

  5. 28 CFR 0.138 - Federal Bureau of Investigation, Drug Enforcement Administration, Bureau of Alcohol, Tobacco...

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Federal Bureau of Investigation, Drug Enforcement Administration, Bureau of Alcohol, Tobacco, Firearms, and Explosives, Bureau of Prisons, Federal... Justice Programs, Executive Office for Immigration Review, Executive Office for United States...

  6. The etiology and drug therapy of kinesia: investigations by means of the coriolis effect under cyclizine.

    Science.gov (United States)

    Reicke, N

    1976-01-01

    The typical symptoms of kinesia were produced in 30 healthy test subjects by means of the Coriolis effect and the effect of cyclizine upon them was investigated in a single blind trial. The drug showed a clear effect on the autonomic symptoms (nausea) while there was no evidence of inhibition of the peripheral vestibular function.

  7. School Bullying and Drug Use Later in Life: A Meta-Analytic Investigation

    Science.gov (United States)

    Ttofi, Maria M.; Farrington, David P.; Lösel, Friedrich; Crago, Rebecca V.; Theodorakis, Nikolaos

    2016-01-01

    The main aim of this article is to investigate whether there is a significant long-term association between bullying at school and drug use later in life. A meta-analysis is presented based on results from major prospective longitudinal studies with available unadjusted and adjusted effect sizes. Results are based on thorough systematic searches…

  8. 21 CFR 312.8 - Charging for investigational drugs under an IND.

    Science.gov (United States)

    2010-04-01

    ... charge for an approved drug obtained from another entity not affiliated with the sponsor for use as part..., if demonstrated in the clinical investigations, would provide a significant advantage over available... or protocol, complying with IND reporting requirements, and other administrative costs...

  9. Carboxymethyl guar gum nanoparticles for drug delivery applications: Preparation and preliminary in-vitro investigations

    Energy Technology Data Exchange (ETDEWEB)

    Dodi, G., E-mail: gianina.dodi@yahoo.co.uk [“Gheorghe Asachi” Technical University of Iasi (Romania); SCIENT — Research Centre for Instrumental Analysis, Bucharest (Romania); Pala, A. [University of Sassari, Sassari (Italy); Barbu, E. [University of Portsmouth, Portsmouth (United Kingdom); Peptanariu, D. [“Petru Poni” Institute of Macromolecular Chemistry, Iasi (Romania); Hritcu, D.; Popa, M.I. [“Gheorghe Asachi” Technical University of Iasi (Romania); Tamba, B.I. [“Gr. T. Popa” University of Medicine and Pharmacy, Iasi (Romania)

    2016-06-01

    Carboxymethyl guar gum (CMGG) synthesized from commercially available polysaccharide was formulated into nanoparticles via ionic gelation using trisodium trimetaphosphate (STMP) as cross-linking agent. Characterisation using a range of analytical techniques (FTIR, NMR, GPC, TGA and DLS) confirmed the CMGG structure and revealed the effect of the CMGG and STMP concentration on the main characteristics of the obtained nanoformulations. The average nanoparticle diameter was found to be around 208 nm, as determined by dynamic light scattering (DLS) and confirmed by scanning electron microscopy (SEM) and nanoparticle tracking analysis (NTA). Experiments using simulated gastric and intestinal fluids evidenced significant pH-dependent drug release behaviour of the nanoformulations loaded with Rhodamine B (RhB) as a model drug (loading capacity in excess of 83%), as monitored by UV–Vis. While dose-dependent cytotoxicity was observed, the nanoformulations appeared completely non-toxic at concentrations below 0.3 mg/mL. Results obtained so far suggest that carboxymethylated guar gum nanoparticles formulated with STMP warrant further investigations as polysaccharide based biocompatible drug nanocarriers. - Highlights: • Carboxymethyl guar gum nanoparticles preparation by ionic gelation • The optimum synthesis system designed particles around 200 nm • The nanoformulations appeared completely non-toxic at specific concentrations • The loaded formulations evidenced significant pH-dependent drug release behaviour • The results encourage further investigations as polysaccharidic drug nanocarriers.

  10. Numerical modelling and experimental investigation of drug release from layered silicone matrix systems.

    Science.gov (United States)

    Snorradóttir, Bergthóra S; Jónsdóttir, Fjóla; Sigurdsson, Sven Th; Thorsteinsson, Freygardur; Másson, Már

    2013-07-16

    Medical devices and polymeric matrix systems that release drugs or other bioactive compounds are of interest for a variety of applications. The release of the drug can be dependent on a number of factors such as the solubility, diffusivity, dissolution rate and distribution of the solid drug in the matrix. Achieving the goal of an optimal release profile can be challenging when relying solely on traditional experimental work. Accurate modelling complementing experimentation is therefore desirable. Numerical modelling is increasingly becoming an integral part of research and development due to the significant advances in computer simulation technology. This work focuses on numerical modelling and investigation of multi-layered silicone matrix systems. A numerical model that can be used to model multi-layered systems was constructed and validated by comparison with experimental data. The model could account for the limited dissolution rate and effect of the drug distribution on the release profiles. Parametric study showed how different factors affect the characteristics of drug release. Multi-layered medical silicone matrices were prepared in special moulds, where the quantity of drug in each layer could be varied, and release was investigated with Franz-diffusion cell setup. Data for long-term release was fitted to the model and the full depletion of the system predicted. The numerical model constructed for this study, whose input parameters are the diffusion, effective dissolution rate and dimensional solubility coefficients, does not require any type of steady-state approximation. These results indicate that numerical model can be used as a design tool for development of controlled release systems such as drug-loaded medical devices.

  11. Tribological investigation of a functional medical textile with lubricating drug-delivery finishing.

    Science.gov (United States)

    Gerhardt, L-C; Lottenbach, R; Rossi, R M; Derler, S

    2013-08-01

    Textile-based drug delivery systems have a high potential for innovative medical and gerontechnological applications. In this study, the tribological behaviour and lubrication properties of a novel textile with drug delivery function/finishing was investigated by means of friction experiments that simulated cyclic dynamic contacts with skin under dry and wet conditions. The textile drug delivery system is based on a loadable biopolymer dressing on a polyester (PES) woven fabric. The fabrics were finished with low (LC) and highly cross-linked (HC) polysaccharide dressings and investigated in the unloaded condition as well as loaded with phytotherapeutic substances. The mechanical resistance and possible abrasion of the functional coatings on the textile substrate were assessed by friction measurements and scanning electron microscopical analyses. Under dry contact conditions, all investigated fabrics (PES substrate alone and textiles with loaded and unloaded dressings) showed generally low friction coefficients (0.20-0.26). Under wet conditions, the measured friction coefficients were typically higher (0.34-0.51) by a factor of 1.5-2. In the wet condition, both loaded drug delivery textiles exhibited 7-29% lower friction (0.34-0.41) than the PES fabric with unloaded dressings (0.42-0.51), indicating pronounced lubrication effects. The lubrication effects as well as the abrasion resistance of the studied textiles with drug delivery function depended on the degree of dilution of the phytotherapeutic substances. Lubricating formulations of textile-based drug delivery systems which reduce friction against the skin might be promising candidates for advanced medical textile finishes in connection with skin care and wound (decubitus ulcer) prevention.

  12. Treating Clostridium difficile infections: Should fecal microbiota transplantation be reclassified from investigational drug to human tissue?

    Directory of Open Access Journals (Sweden)

    Mark Stuntz

    2015-10-01

    Full Text Available Fecal microbiota transplantation (FMT has emerged as a highly effective treatment for Clostridium difficile infection (CDI, the most frequent cause of hospital-acquired infectious diarrhea in developed countries and the cause of nearly 30,000 annual deaths in the US. FMT is proving to be more effective at treating CDI than traditional antibacterial therapy, and reduces the exposure of valuable antibiotics to potential resistance. A systematic review to assess the efficacy of FMT for CDI treatment showed that across all studies for recurrent CDI, symptom resolution was observed in 85% of patients. The United States Food and Drug Administration currently classifies FMT as an investigational drug, which imparts overly restrictive regulations that are impossible to apply to FMT in the same manner as conventional drugs. Reclassification of FMT to a human cell, tissue, and cellular and tissue-based product could potentially expand access to this important treatment while maintaining rigorous safety standards.

  13. One and done: Reasons principal investigators conduct only one FDA-regulated drug trial

    Directory of Open Access Journals (Sweden)

    Amy Corneli, PhD, MPH

    2017-06-01

    Full Text Available Concerns have been raised over the high turnover rate for clinical investigators. Using the U.S. Food and Drug Administration's (FDA Bioresearch Monitoring Information System database, we conducted an online survey to identify factors that affect principal investigators' (PIs decisions to conduct only a single FDA-regulated drug trial. Of the 201 PIs who responded, 54.2% were classified as “one-and-done.” Among these investigators, 28.9% decided for personal reasons to not conduct another trial, and 44.4% were interested in conducting another trial, but no opportunities were available. Three categories of broad barriers were identified as generally burdensome or challenging by the majority of investigators: 1 workload balance (balancing trial implementation with other work obligations and opportunities (63.8%; 2 time requirements (time to initiate and implement trial; investigator and staff time (63.4%; and 3 data and safety reporting (56.5%. Additionally, 46.0% of investigators reported being generally unsatisfied with finance-related issues. These same top three barriers also affected investigators' decisions to no longer conduct FDA-regulated trials. Our findings illuminate three key aspects of investigator turnover. First, they confirm that investigator turnover occurs, as more than half of respondents were truly “one-and-done.” Second, because a large proportion of respondents wanted to conduct more FDA-regulated trials but lacked opportunities to do so, mechanisms that match interested investigators with research sponsors are needed. Third, by focusing on the barriers we identified that affected investigators' decisions to no longer conduct FDA-regulated trials, future efforts to reduce investigator turnover can target issues that matter the most to investigators.

  14. Advances in Engineered Liver Models for Investigating Drug-Induced Liver Injury

    Science.gov (United States)

    Lin, Christine

    2016-01-01

    Drug-induced liver injury (DILI) is a major cause of drug attrition. Testing drugs on human liver models is essential to mitigate the risk of clinical DILI since animal studies do not always suffice due to species-specific differences in liver pathways. While primary human hepatocytes (PHHs) can be cultured on extracellular matrix proteins, a rapid decline in functions leads to low sensitivity (<50%) in DILI prediction. Semiconductor-driven engineering tools now allow precise control over the hepatocyte microenvironment to enhance and stabilize phenotypic functions. The latest platforms coculture PHHs with stromal cells to achieve hepatic stability and enable crosstalk between the various liver cell types towards capturing complex cellular mechanisms in DILI. The recent introduction of induced pluripotent stem cell-derived human hepatocyte-like cells can potentially allow a better understanding of interindividual differences in idiosyncratic DILI. Liver models are also being coupled to other tissue models via microfluidic perfusion to study the intertissue crosstalk upon drug exposure as in a live organism. Here, we review the major advances being made in the engineering of liver models and readouts as they pertain to DILI investigations. We anticipate that engineered human liver models will reduce drug attrition, animal usage, and cases of DILI in humans. PMID:27725933

  15. Investigation of Polymer-Surfactant and Polymer-Drug-Surfactant Miscibility for Solid Dispersion.

    Science.gov (United States)

    Gumaste, Suhas G; Gupta, Simerdeep Singh; Serajuddin, Abu T M

    2016-09-01

    In a solid dispersion (SD), the drug is generally dispersed either molecularly or in the amorphous state in polymeric carriers, and the addition of a surfactant is often important to ensure drug release from such a system. The objective of this investigation was to screen systematically polymer-surfactant and polymer-drug-surfactant miscibility by using the film casting method. Miscibility of the crystalline solid surfactant, poloxamer 188, with two commonly used amorphous polymeric carriers, Soluplus® and HPMCAS, was first studied. Then, polymer-drug-surfactant miscibility was determined using itraconazole as the model drug, and ternary phase diagrams were constructed. The casted films were examined by DSC, PXRD and polarized light microscopy for any crystallization or phase separation of surfactant, drug or both in freshly prepared films and after exposure to 40°C/75% RH for 7, 14, and 30 days. The miscibility of poloxamer 188 with Soluplus® was <10% w/w, while its miscibility with HPMCAS was at least 30% w/w. Although itraconazole by itself was miscible with Soluplus® up to 40% w/w, the presence of poloxamer drastically reduced its miscibility to <10%. In contrast, poloxamer 188 had minimal impact on HPMCAS-itraconazole miscibility. For example, the phase diagram showed amorphous miscibility of HPMCAS, itraconazole, and poloxamer 188 at 54, 23, and 23% w/w, respectively, even after exposure to 40°C/75% RH for 1 month. Thus, a relatively simple and practical method of screening miscibility of different components and ultimately physical stability of SD is provided. The results also identify the HPMCAS-poloxamer 188 mixture as an optimal surface-active carrier system for SD.

  16. Coatings of Eudragit® RL and L-55 Blends: Investigations on the Drug Release Mechanism.

    Science.gov (United States)

    Wulff, Robert; Leopold, Claudia S

    2016-04-01

    In a previous study, generally lower drug release rates from RL:L55 blend coated pellets in neutral/basic release media than in acidic release media were reported. The aim of this study was to obtain information on the drug release mechanism of solid dosage forms coated with blends of Eudragit® RL (RL) and Eudragit® L-55 (L55). Swelling experiments with free films were analyzed spectroscopically and gravimetrically to identify the physicochemical cause for this release behavior. With Raman spectroscopy, the swelling of copolymer films could be monitored. IR spectroscopic investigations on RL:L55 blends immersed in media at pH 6.8 confirmed the formation of interpolyelectrolyte complexes (IPECs) that were not detectable after swelling in hydrochloric acid pH 1.2. Further investigations revealed that these IPECs decreased the extent of ion exchange between the quaternary ammonium groups of RL and the swelling media. This is presumably the reason for the previously reported decreased drug permeability of RL:L55 coatings in neutral/basic media as ion exchange is the determining factor in drug release from RL coated dosage forms. Gravimetric erosion studies confirmed that L55 was not leached out of the film blends during swelling in phosphate buffer pH 6.8. In contrast to all other investigated films, the 4:1 (RL:L55) blend showed an extensive swelling within 24 h at pH 6.8 which explains the reported sigmoidal release behavior of 4:1 blend coated pellets. These results help to understand the release behavior of RL:L55 blend coated solid dosage forms.

  17. Intelligence and High Intensity Drug Trafficking Areas (HIDTA’s): A Critical Evaluation of the HIDTA Investigative Support Center (ISC)

    Science.gov (United States)

    2004-09-01

    The purpose of this thesis is to evaluate critically the ongoing reform of the High Intensity Drug Trafficking Area (HIDTA) Investigative Support...or Fusion Center for information sharing between agencies investigating crimes relating to drug trafficking , terrorism, and money laundering.

  18. Investigation of interaction of human platelet membrane components with anticoagulant drugs Abciximab and Eptifibatide.

    Directory of Open Access Journals (Sweden)

    Anna Sankiewicz

    2011-04-01

    Full Text Available Abciximab (Abci and eptifibatide (Epti are antiaggregate drugs which may reduce thrombotic complications in acute coronary syndromes. The aim of this work was the investigation of the interaction between the phospholipid-GPIIb/IIIa glycoprotein complex and Abci or Epti, and the influence of these drugs on the phospholipid ratio in the platelet membrane. The interaction between the phospholipid-GPIIb/IIIa glycoprotein complex and antiaggregate drugs were investigated using the Surface Plasmon Resonance Imaging technique (SPRI. Phospholipids phosphatidylinositol (PI, phosphatidylserine (PS, phosphatidylethanolamine (PE, phosphatidylcholine (PC and sphingomyelin (SM were first immobilized onto the gold chip surface. The phospholipid ratio in the platelet membrane was determined by the HPLC. Only PI, PS, PE and PC were determined. Human platelets treated 'in vitro' with Abci or Epti exhibit changes in the phospholipid ratio in the platelet membrane. The ratio of PS decreases and PC rises. The SPRI distinctly shows interactions between phospholipids and glycoprotein GPIIb/IIIa, and between the phospholipid-glycoprotein GPIIb/IIIa complex and Abci or Epti. The interaction between phospholipids and glycoprotein GPIIb/IIIa is growing in the sequence: PI

  19. Investigations on nanoconfinement of low-molecular antineoplastic agents into biocompatible magnetic matrices for drug targeting.

    Science.gov (United States)

    Tomoiaga, Alina Maria; Cioroiu, Bogdan Ionel; Nica, Valentin; Vasile, Aurelia

    2013-11-01

    Magnetic mesoporous silica nanoparticles are employed as biocompatible matrices to host low-molecular antineoplastic drugs. 5-Fluorouracil is a well-known antimetabolite drug used to treat many malignancies: colon, rectal, breast, head and neck, pancreatic, gastric, esophageal, liver and G-U (bladder, penile, vulva, prostate), skin cancers (basal cell and keratosis). Unfortunately severe gastrointestinal, hematological, neural, cardiac and dermatological toxic effects are often registered due to its cytotoxicity. Thus, this work focuses on development of a magnetic silica nanosystem, capable of hosting high amounts of 5-fluorouracil and delivers it in a targeted manner, under the influence of external magnetic field. There are few reports on nanoconfinement of this particular small molecule antimetabolite on mesoporous silica hosts. Therefore we have investigated different ways to confine high amounts of 5-FU within amino-modified and non-modified mesopores of the silica shell, from water and ethanol, under magnetic stirring and ultrasound irradiation. Also, we have studied the adsorption process from water as a function of pH in order to rationalize drug-support interactions. It is shown that nature of the solvent has great influence on diffusion of small molecules into mesopores, which is slower from alcoholic solutions. More importantly, sonication is proven as an excellent alternative to long adsorption tests, since the time necessary to reach equilibrium is drastically reduced to 1h and higher amounts of drug may be immobilized within the mesopores of amino-modified magnetic silica nanoparticles. These results are highly important for optimization of drug immobilization process in order to attain desired release profile. Copyright © 2013 Elsevier B.V. All rights reserved.

  20. Caveat medicus: consequences of federal investigations of marketing activities of pharmaceutical suppliers of prostate cancer drugs.

    Science.gov (United States)

    McKoy, June M; Lyons, E Allison; Obadina, Eniola; Carson, Kenneth; Pickard, A Simon; Schellhammer, Paul; McLeod, David; Boyd, Cynthia E; McWilliams, Norene; Sartor, Oliver; Schumock, Glen T; McCaffery, Kathryn; Bennett, Charles L

    2005-12-01

    In the course of recent health care fraud investigations against TAP Pharmaceuticals (Lake Forest, IL) and AstraZeneca International (London, United Kingdom), each pled guilty to one violation of the Prescription Drug Marketing Act, settled claims related to alleged violations of the False Claims Act without admitting guilt, and paid fines, settlements for liabilities, and reimbursements of dollar 850 million and dollar 355 million, respectively. In a unique aspect of these cases, federal investigators brought criminal charges against 14 TAP employees and investigated the billing practices of several urologists. These investigations resulted in guilty pleas from both urologists and industry employees relative to the Prescription Drug Marketing Act or the False Claims Act and probationary sentences with payments of fines and restitution to the government for urologists who cooperated with federal investigations. One uncooperative urologist was found guilty of violating the Federal False Claims Act and sentenced to 6 months of home arrest, excluded from Medicare for 5 years, required to provide 600 hours of free medical care to indigent patients and patients covered by Medicare or Medicaid, and paid fines and restitution to the government. The cases against TAP and AstraZeneca have been followed by federal and state investigations of allegedly illegal marketing practices of other pharmaceutical firms and have resulted in negotiated settlements of dollar 3.8 billion and dollar 71.5 million, respectively. Believing that an Average Wholesale Price-based reimbursement system was an important driving factor for these marketing activities, Medicare has shifted to an Average Sales Price-based reimbursement system. This is expected to greatly impact the practice of outpatient oncology nationwide.

  1. Using Moessbauer spectroscopy as key technique in the investigation of nanosized magnetic particles for drug delivery

    Energy Technology Data Exchange (ETDEWEB)

    Morais, P. C., E-mail: pcmor@unb.br [Universidade de Brasilia, Nucleo de Fisica Aplicada, Instituto de Fisica (Brazil)

    2008-01-15

    This paper describes how cobalt ferrite nanoparticles, suspended as ionic or biocompatible magnetic fluids, can be used as a platform to built complex nanosized magnetic materials, more specifically magnetic drug delivery systems. In particular, the paper is addressed to the discussion of the use of the Moessbauer spectroscopy as an extremely useful technique in supporting the investigation of key aspects related to the properties of the hosted magnetic nanosized particle. Example of the use of the Moessbauer spectroscopy in accessing information regarding the nanoparticle modification due to the empirical process which provides long term chemical stability is included in the paper.

  2. Investigation of drug distribution in tablets using surface enhanced Raman chemical imaging.

    Science.gov (United States)

    Firkala, Tamás; Farkas, Attila; Vajna, Balázs; Farkas, István; Marosi, György

    2013-03-25

    This paper reports the first application of surface enhanced Raman chemical imaging on pharmaceutical tablets containing the active ingredient (API) in very low concentrations. Taking advantage of the extremely intensive Raman signals in the presence of silver colloids, image aquisition time was radically decreased. Moreover, the investigation of drug distribution below the detection limit of regular micro-Raman spectrometry was made feasible. The characteristics of different manufacturing technologies could be revealed at very low API concentrations by using chemometric methods for processing and evaluating the large number of varying spectra provided with this imaging method.

  3. Energetics investigation on encapsulation of protein/peptide drugs in carbon nanotubes.

    Science.gov (United States)

    Chen, Qu; Wang, Qi; Liu, Ying-Chun; Wu, Tao; Kang, Yu; Moore, Joshua D; Gubbins, Keith E

    2009-07-07

    This work focuses on the dynamic properties and energetics of the protein/peptide drug during its transport through carbon nanotubes (CNTs). A systematic study was performed on the interaction between the peptide and the CNTs. In the molecular dynamics (MD) simulations, the protein/peptide molecule Zadaxin is observed to be encapsulated inside the nanotube after its spontaneous insertion and oscillates around the center of the tube, where the van der Waals interaction energy is observed to be a minimum. Furthermore, it is found by performing steered MD simulations that the pulling force applied to the peptide reaches a maximum value, which demonstrates the ability of the CNTs to trap protein/peptide drugs. Such effects, attributed to van der Waals interactions, can be influenced by varying the lengths and diameters of the CNTs. Longer nanotubes provide a broader area to trap the peptide, while smaller nanotubes are able to encapsulate the peptide with a deeper interaction energy well. This investigation provides insights into nanoscale pharmaceutical drug delivery devices.

  4. Investigation of interaction of human platelet membrane components with anticoagulant drugs Abciximab and Eptifibatide

    Directory of Open Access Journals (Sweden)

    Ewa Gorodkiewicz

    2010-04-01

    Full Text Available Abciximab (Abci and eptifibatide (Epti are antiaggregate drugs which may reduce thrombotic complications inacute coronary syndromes. The aim of this work was the investigation of the interaction between the phospholipid-GPIIb/IIIa glycoprotein complex and Abci or Epti, and the influence of these drugs on the phospholipid ratio in the plateletmembrane. The interaction between the phospholipid-GPIIb/IIIa glycoprotein complex and antiaggregate drugs were investigatedusing the Surface Plasmon Resonance Imaging technique (SPRI. Phospholipids phosphatidylinositol (PI, phosphatidylserine(PS, phosphatidylethanolamine (PE, phosphatidylcholine (PC and sphingomyelin (SM were first immobilizedonto the gold chip surface. The phospholipid ratio in the platelet membrane was determined by the HPLC. Only PI,PS, PE and PC were determined. Human platelets treated 'in vitro' with Abci or Epti exhibit changes in the phospholipidratio in the platelet membrane. The ratio of PS decreases and PC rises. The SPRI distinctly shows interactions between phospholipidsand glycoprotein GPIIb/IIIa, and between the phospholipid-glycoprotein GPIIb/IIIa complex and Abci or Epti.The interaction between phospholipids and glycoprotein GPIIb/IIIa is growing in the sequence: PI<

  5. Carboxymethyl guar gum nanoparticles for drug delivery applications: Preparation and preliminary in-vitro investigations.

    Science.gov (United States)

    Dodi, G; Pala, A; Barbu, E; Peptanariu, D; Hritcu, D; Popa, M I; Tamba, B I

    2016-06-01

    Carboxymethyl guar gum (CMGG) synthesized from commercially available polysaccharide was formulated into nanoparticles via ionic gelation using trisodium trimetaphosphate (STMP) as cross-linking agent. Characterisation using a range of analytical techniques (FTIR, NMR, GPC, TGA and DLS) confirmed the CMGG structure and revealed the effect of the CMGG and STMP concentration on the main characteristics of the obtained nanoformulations. The average nanoparticle diameter was found to be around 208 nm, as determined by dynamic light scattering (DLS) and confirmed by scanning electron microscopy (SEM) and nanoparticle tracking analysis (NTA). Experiments using simulated gastric and intestinal fluids evidenced significant pH-dependent drug release behaviour of the nanoformulations loaded with Rhodamine B (RhB) as a model drug (loading capacity in excess of 83%), as monitored by UV-Vis. While dose-dependent cytotoxicity was observed, the nanoformulations appeared completely non-toxic at concentrations below 0.3 mg/mL. Results obtained so far suggest that carboxymethylated guar gum nanoparticles formulated with STMP warrant further investigations as polysaccharide based biocompatible drug nanocarriers.

  6. Pathogenesis of Brain Edema and Investigation into Anti-Edema Drugs

    Science.gov (United States)

    Michinaga, Shotaro; Koyama, Yutaka

    2015-01-01

    Brain edema is a potentially fatal pathological state that occurs after brain injuries such as stroke and head trauma. In the edematous brain, excess accumulation of extracellular fluid results in elevation of intracranial pressure, leading to impaired nerve function. Despite the seriousness of brain edema, only symptomatic treatments to remove edema fluid are currently available. Thus, the development of novel anti-edema drugs is required. The pathogenesis of brain edema is classified as vasogenic or cytotoxic edema. Vasogenic edema is defined as extracellular accumulation of fluid resulting from disruption of the blood-brain barrier (BBB) and extravasations of serum proteins, while cytotoxic edema is characterized by cell swelling caused by intracellular accumulation of fluid. Various experimental animal models are often used to investigate mechanisms underlying brain edema. Many soluble factors and functional molecules have been confirmed to induce BBB disruption or cell swelling and drugs targeted to these factors are expected to have anti-edema effects. In this review, we discuss the mechanisms and involvement of factors that induce brain edema formation, and the possibility of anti-edema drugs targeting them. PMID:25941935

  7. Pathogenesis of Brain Edema and Investigation into Anti-Edema Drugs

    Directory of Open Access Journals (Sweden)

    Shotaro Michinaga

    2015-04-01

    Full Text Available Brain edema is a potentially fatal pathological state that occurs after brain injuries such as stroke and head trauma. In the edematous brain, excess accumulation of extracellular fluid results in elevation of intracranial pressure, leading to impaired nerve function. Despite the seriousness of brain edema, only symptomatic treatments to remove edema fluid are currently available. Thus, the development of novel anti-edema drugs is required. The pathogenesis of brain edema is classified as vasogenic or cytotoxic edema. Vasogenic edema is defined as extracellular accumulation of fluid resulting from disruption of the blood-brain barrier (BBB and extravasations of serum proteins, while cytotoxic edema is characterized by cell swelling caused by intracellular accumulation of fluid. Various experimental animal models are often used to investigate mechanisms underlying brain edema. Many soluble factors and functional molecules have been confirmed to induce BBB disruption or cell swelling and drugs targeted to these factors are expected to have anti-edema effects. In this review, we discuss the mechanisms and involvement of factors that induce brain edema formation, and the possibility of anti-edema drugs targeting them.

  8. Investigation of naproxen drug using mass spectrometry, thermal analyses and semi-empirical molecular orbital calculation

    Directory of Open Access Journals (Sweden)

    M.A. Zayed

    2017-03-01

    Full Text Available Naproxen (C14H14O3 is a non-steroidal anti-inflammatory drug (NSAID. It is important to investigate its structure to know the active groups and weak bonds responsible for medical activity. In the present study, naproxen was investigated by mass spectrometry (MS, thermal analysis (TA measurements (TG/DTG and DTA and confirmed by semi empirical molecular orbital (MO calculation, using PM3 procedure. These calculations included, bond length, bond order, bond strain, partial charge distribution, ionization energy and heat of formation (ΔHf. The mass spectra and thermal analysis fragmentation pathways were proposed and compared to select the most suitable scheme representing the correct fragmentation pathway of the drug in both techniques. The PM3 procedure reveals that the primary cleavage site of the charged molecule is the rupture of the COOH group (lowest bond order and high strain which followed by CH3 loss of the methoxy group. Thermal analysis of the neutral drug reveals a high response to the temperature variation with very fast rate. It decomposed in several sequential steps in the temperature range 80–400 °C. These mass losses appear as two endothermic and one exothermic peaks which required energy values of 255.42, 10.67 and 371.49 J g−1 respectively. The initial thermal ruptures are similar to that obtained by mass spectral fragmentation (COOH rupture. It was followed by the loss of the methyl group and finally by ethylene loss. Therefore, comparison between MS and TA helps in selection of the proper pathway representing its fragmentation. This comparison is successfully confirmed by MO-calculation.

  9. Investigation of drugs responsible for perioperative anaphylactic reactions using cellular allergen stimulation test

    Institute of Scientific and Technical Information of China (English)

    Xin Xin; Zou Yi; Xing Lijiao; Yin Jia; Gu Jianqing; Wang Zixi; Huang Yuguang

    2014-01-01

    Background Anaphylactic reactions during anesthesia and operation are common and life threatening.Follow-up investigation is necessary for avoiding potential re-exposure of the patients to the offending drugs.The purpose of this study was to assess cellular allergen stimulation test (CAST) as a diagnostic instrument in immunoglobulin E (IgE)-and non-lgE-mediated anaphylactic reactions.Methods This study included 25 patients who developed perioperative anaphylactic reactions and 10 subjects that tolerated anesthetics and other drugs during perioperative period from September 2009 to October 2013 in Peking Union Medical College Hospital.We performed skin tests and flow cytometric analysis of basophil activation-based CAST in all subjects.Results Of the 25 patients,17 had IgE-mediated anaphylactic reactions (causative agent identified by skin tests) and 8 had non-lgE-mediated anaphylactic reactions (negative skin tests).CAST showed a sensitivity of 42.9%,specificity of 90%,and negative predictive value of 80.6% for neuromuscular blocking agents.Conclusions CAST may be useful for the diagnosis of anaphylactic reactions during perioperative period.Our findings call for further investigation to increase the sensitivity of the test.

  10. The Majority of Expedited Investigational New Drug Safety Reports Are Uninformative.

    Science.gov (United States)

    Jarow, Jonathan P; Casak, Sandra; Chuk, Meredith; Ehrlich, Lori A; Khozin, Sean

    2016-05-01

    Sponsors of human drug and biologic products subject to an investigational new drug (IND) application are required to distribute expedited safety reports of serious and unexpected suspected adverse reactions to participating investigators and the FDA to assure the protection of human subjects participating in clinical trials. On September 29, 2010, the FDA issued a final rule amending its regulations governing expedited IND safety reporting requirements that revised the definitions used for reporting and clarified when to submit relevant and useful information to reduce the number of uninformative reports distributed by sponsors. From January 1, 2006, to December 31, 2014, the FDA's Office of Hematology and Oncology Products received an average of 17,686 expedited safety reports per year. An analysis of FDA submissions by commercial sponsors covering this time period suggested a slight increase in the number of expedited safety reports per IND per year after publication of the final rule. An audit of 160 randomly selected expedited safety reports submitted to the FDA's Office of Hematology and Oncology Products in 2015 revealed that only 22 (14%) were informative. The submission of uninformative expedited safety reports by commercial sponsors of INDs continues to be a significant problem that can compromise detection of valid safety signals. Clin Cancer Res; 22(9); 2111-3. ©2016 AACR.

  11. The Investigation of Drug Addiction Potential among Medical Students: Role of Subjective Components of Anger

    Directory of Open Access Journals (Sweden)

    A Agha Yusefi

    2016-02-01

    Full Text Available Objective: Given that drug addiction is not merely related to a specific individual or group, and few studies have investigated the role of anger in the development of drug addiction, this study was done to investigate the role of the components of anger in predicting addiction potential. Method: A descriptive-correlation research design was used for the conduct of this study. The number of 309 medical students in Kermanshah city was selected using stratified cluster sampling and completed Spielberger's State-Trait Anger Scale (STAS and Zargar’s addiction potential questionnaire. Results: The results showed that ate anger, trait anger, anger expression-out (AXO, anger expression-in (AXI, the overall index for the expression of anger were significantly associated with addiction potential. Similarly, anger control-out (ACO, anger control-in (ACI were correlated with addiction potential. In addition, the regression analysis results indicated that the components of state anger and anger expression-in (AXI together can predict 35% of changes related to addiction potential. Conclusion: State anger and anger expression-in (AXI as subjective components of anger have a significant role in predicting addiction potential among medical students. Anger management programs for medical students, as the most important segment of the society in the field of public health, are recommended to assign more credit to these two components.

  12. Investigation on infection of hepatitis G virus in 105 cases of drug abusers

    Institute of Scientific and Technical Information of China (English)

    Rui Xing Zhong; Hong Tao Luo; Rui Xian Zhang; Guo Rong Li; Ling Lu

    2000-01-01

    AIM To investigate the infection of hepatitis G virus (HGV) in 105 cases of drug abusers.MATERIALS AND METHODS One hundred and five heroin addicts including 85 males and 20 females,aged from 17a to 45a old, mean age 26.3a±5.8a were observed. Duration of the drug abusing was rangedfrom 5 mo to 168 mo with mean 37.5 mo±23.6 mo. Seventy-five cases accepted the drug by intravenousinjection only, 30 others by both intravenous and scalded inhaling ways. All cases had no history of bloodtransfusion. ① Detection of HGV-RNA: total RNA was extracted from serum by the acid quanidinum thiocyanate-phenol-ethanol method, the 5'terminal non-coded region of HGV-RNA was amplified by nested reversetranscription-PCR, ② anti-HAV-IgM, HBsAg, anti-HCV, HDAg, anti-HD, anti-HD-IgM and anti-HEVwere detected by ELISA. Reagents were provided by Shenzhen Moon Bay Biologic Company. ③ Hepaticfunctions were determined by Hitachi 7510 automatic analyzer.RESULTS (① Incidence of HGV infection: 25(23.8%) of 105 drug abusers, 21 men and 4 women,wereinfected with HGV. The mean drug taking time of HGV infected cases were 38.6 mo±19.9 mo, it is similarwith the mean duration of drug abusing, 37.7 mo±24.6 mo (P>0.05), of those cases without HGVinfection. ② Superinfection of HGV with hepatitis B virus (HBV) or hepatitis C virus (HCV): 26 (24.7%)of 105 addicts were infected with HBV and 68 (64.8%) with HCV. Among 25 cases infected with HGV, 8(32%) of them were infected with HGV alone, 6(24.0%) were superinfected with HCV, 2(8.0%) withHBVand 9(36.0%) with HCV and HBV. Thus, 17(68.0%) of 25 cases infected with HGV weresuperinfected with HCV and/or HBV. ③ Hepatic function tests: The total serum bilirubin levels of all 105cases were less than 20 umol/L. The ALT levels of 30(28.6%) cases were more than 40 U/L and amongthem, 1 case was infected with HGV only, 1 was superinfected with HGV and HBV, 3 with HGV and HCV,7 with HGV, HBV and HCV respectively. Meanwhile also among the cases with abnormal

  13. Clinical studies involving probiotics: when FDA's investigational new drug rubric applies-and when it may not.

    Science.gov (United States)

    Degnan, Fred H

    2012-01-01

    Researchers from a diverse array of scientific disciplines have focused and continue to focus on opportunities and areas for responsible clinical research involving the possible beneficial health effects of "probiotics." Investigators and researchers should be aware that not all clinical research involving probiotics reasonably falls within the requirements of the "investigational new drug" (IND) rubric administered and enforced by the US Food and Drug Administration. In determining whether an IND application is required before a clinical study may lawfully commence, investigators and researchers as well as institutional review boards should consider the regulatory classification, e.g., "drug," "new drug," "food," "food additive," "dietary supplement," etc. that applies to the substance under investigation. A potential probiotic product can fall along a continuum of regulatory classifications, each having implications on the nature and degree of regulatory requirements for clinical research and, ultimately, for claim substantiation and market access.

  14. Artesunate: investigational drug for the treatment of severe falciparum malaria in Hawai'i.

    Science.gov (United States)

    Callender, David M; Hsue, Gunther

    2011-04-01

    There are hundreds of millions of cases of malaria each year worldwide resulting in a million deaths. These deaths are mostly due to Plasmodium falciparum. The only Federal Drug Administration approved treatment for severe malaria is intravenous quinidine gluconate. Intravenous quinidine is increasingly unavailable in the United States. In 2007, the Center for Disease Control and Prevention implemented an investigational new drug protocol to allow the use of intravenous artesunate for cases of severe malaria in the United States. The authors present such a case treated under this protocol at Tripler Army Medical Center, Hawai'i. A 49-year-old man presented to Tripler Army Medical Center, Hawai'i in February 2009 with a one-month history of fever, chills, and weight loss. He recently travelled to multiple malaria endemic areas. Physical examination was significant for fever and prostration. Laboratory studies revealed anemia, thrombocytopenia, and a high parasite load of Plasmodium falciparum. A strategic network was activated to obtain and administer intravenous artesunate. His condition rapidly improved as his parasitemia cleared. He was discharged after six days with no adverse medication effects and full recovery upon six-month follow-up. Our patient met the criteria for severe Plasmodium falciparum malaria. He was immediately treated with intravenous artesunate and manifested a quick and durable response to therapy. At present, intravenous artesunate is awaiting Federal Drug Administration approval but available via a strategic network controlled by the Centers for Disease Control and Prevention. This case highlights a common delay in diagnosis, importance of optimal prophylaxis, and attention to travel history as they relate to the development of severe malaria.

  15. Artesunate: Investigational Drug for the Treatment of Severe Falciparum Malaria in Hawai‘i

    Science.gov (United States)

    Hsue, Gunther

    2011-01-01

    Introduction There are hundreds of millions of cases of malaria each year worldwide resulting in a million deaths. These deaths are mostly due to Plasmodium falciparum. The only Federal Drug Administration approved treatment for severe malaria is intravenous quinidine gluconate. Intravenous quinidine is increasingly unavailable in the United States. In 2007, the Center for Disease Control and Prevention implemented an investigational new drug protocol to allow the use of intravenous artesunate for cases of severe malaria in the United States. The authors present such a case treated under this protocol at Tripler Army Medical Center, Hawai‘i. Case Report A 49-year-old man presented to Tripler Army Medical Center, Hawai‘i in February 2009 with a one-month history of fever, chills, and weight loss. He recently travelled to multiple malaria endemic areas. Physical examination was significant for fever and prostration. Laboratory studies revealed anemia, thrombocytopenia, and a high parasite load of Plasmodium falciparum. A strategic network was activated to obtain and administer intravenous artesunate. His condition rapidly improved as his parasitemia cleared. He was discharged after six days with no adverse medication effects and full recovery upon six-month follow-up. Discussion Our patient met the criteria for severe Plasmodium falciparum malaria. He was immediately treated with intravenous artesunate and manifested a quick and durable response to therapy. At present, intravenous artesunate is awaiting Federal Drug Administration approval but available via a strategic network controlled by the Centers for Disease Control and Prevention. This case highlights a common delay in diagnosis, importance of optimal prophylaxis, and attention to travel history as they relate to the development of severe malaria. PMID:21785506

  16. Investigation of anti-motion sickness drugs in the squirrel monkey

    Science.gov (United States)

    Cheung, B. S.; Money, K. E.; Kohl, R. L.; Kinter, L. B.

    1992-01-01

    Early attempts to develop an animal model for anti-motion sickness drugs, using dogs and cats; were unsuccessful. Dogs did not show a beneficial effect of scopolamine (probably the best single anti-motion sickness drug for humans thus far) and the findings in cats were not definitive. The authors have developed an animal model using the squirrel monkey (Saimiri sciureus) of the Bolivian phenotype. Unrestrained monkeys in a small lucite cage were tested in an apparatus that induces motion sickness by combining vertical oscillation and horizontal rotation in a visually unrestricted laboratory environment. Signs of motion sickness were scored using a rating scale. Ten susceptible monkeys (weighing 800-1000 g) were given a total of five tests each, to establish the baseline susceptibility level. Based on the anticholinergic activity of scopolamine, the sensitivity of squirrel monkey to scopolamine was investigated, and the appropriate dose of scopolamine for this species was determined. Then various anti-motion sickness preparations were administered in subsequent tests: 100 ug scopolamine per monkey; 140 ug dexedrine; 50 ug scopolamine plus 70 ug dexedrine; 100 ug scopolamine plus 140 ug dexedrine; 3 mg promethazine; 3 mg promethazine plus 3 mg ephedrine. All these preparations were significantly effective in preventing motion sickness in the monkeys. Ephedrine, by itself, which is marginally effective in humans, was ineffective in the monkeys at the doses tried (0.3-6.0 mg). The squirrel monkey appears to be a good animal model for antimotion sickness drugs. Peripherally acting antihistamines such as astemizole and terfenadine were found to be ineffective, whereas flunarizine, and an arginine vasopressin V1 antagonist, showed significant activity in preventing motion sickness.

  17. Inflation of the type I error: investigations on regulatory recommendations for bioequivalence of highly variable drugs.

    Science.gov (United States)

    Wonnemann, Meinolf; Frömke, Cornelia; Koch, Armin

    2015-01-01

    We investigated different evaluation strategies for bioequivalence trials with highly variable drugs on their resulting empirical type I error and empirical power. The classical 'unscaled' crossover design with average bioequivalence evaluation, the Add-on concept of the Japanese guideline, and the current 'scaling' approach of EMA were compared. Simulation studies were performed based on the assumption of a single dose drug administration while changing the underlying intra-individual variability. Inclusion of Add-on subjects following the Japanese concept led to slight increases of the empirical α-error (≈7.5%). For the approach of EMA we noted an unexpected tremendous increase of the rejection rate at a geometric mean ratio of 1.25. Moreover, we detected error rates slightly above the pre-set limit of 5% even at the proposed 'scaled' bioequivalence limits. With the classical 'unscaled' approach and the Japanese guideline concept the goal of reduced subject numbers in bioequivalence trials of HVDs cannot be achieved. On the other hand, widening the acceptance range comes at the price that quite a number of products will be accepted bioequivalent that had not been accepted in the past. A two-stage design with control of the global α therefore seems the better alternative.

  18. Investigational new drug safety reporting requirements for human drug and biological products and safety reporting requirements for bioavailability and bioequivalence studies in humans. Final rule.

    Science.gov (United States)

    2010-09-29

    The Food and Drug Administration (FDA) is amending its regulations governing safety reporting requirements for human drug and biological products subject to an investigational new drug application (IND). The final rule codifies the agency's expectations for timely review, evaluation, and submission of relevant and useful safety information and implements internationally harmonized definitions and reporting standards. The revisions will improve the utility of IND safety reports, reduce the number of reports that do not contribute in a meaningful way to the developing safety profile of the drug, expedite FDA's review of critical safety information, better protect human subjects enrolled in clinical trials, subject bioavailability and bioequivalence studies to safety reporting requirements, promote a consistent approach to safety reporting internationally, and enable the agency to better protect and promote public health.

  19. Investigation of drug-excipient compatibility using rheological and thermal tools

    Science.gov (United States)

    Trivedi, Maitri R.

    HYPOTHESIS: We plan to investigate a different approach to evaluate drug-excipient physical compatibility using rheological and thermal tools as opposed to commonly used chemical techniques in pharmaceutical industry. This approach offers practical solutions to routinely associated problems arising with API's and commonly used hydrates forms of excipients. ABSTRACT: Drug-Excipient compatibility studies are an important aspect of pre-formulation and formulation development in pharmaceutical research and development. Various approaches have been used in pharmaceutical industry including use of thermal analysis and quantitative assessment of drug-excipient mixtures after keeping the samples under stress environment depending upon the type of formulation. In an attempt to provide better understanding of such compatibility aspect of excipients with different properties of API, various rheological and thermal studies were conducted on binary mixtures of excipients which exist in different hydrates. Dibasic Calcium Phosphate (DCP, anhydrous and dihydrate forms) and Lactose (Lac, anhydrous and monohydrate) were selected with cohesive API's (Acetaminophen and Aspirin). Binary mixtures of DCP and Lac were prepared by addition of 0% w/w to 50% w/w of the API into each powder blend. Rheological and thermal aspects were considered using different approaches such as powder rheometer, rotational shear cell and traditional rheometery approaches like angle of repose (AOR), hausner's ratio (HR) and cares index (CI). Thermal analysis was conducted using modulated differential scanning calorimetry (MDSC) and thermal effusivity. The data suggested that the powder rheometer showed distinctive understanding in the flowability behavior of binary mixtures with addition of increasing proportion of API's than traditional approaches. Thermal approaches revealed the potential interaction of water of crystallization DCP-D with the API (APAP) while such interactions were absent in DCP-A, while

  20. DFT investigation on the tautomerization reaction and NBO analysis of the Acamprosate drug

    Directory of Open Access Journals (Sweden)

    B. Esmaeili

    2015-12-01

    Full Text Available The Acamprosate is a significant drug for alcohol abuse therapy, which may be an effective treatment for tinnitus, too. The Acamprosate has two possible tautomers, Keto and Enol tautomers. Each of the tautomers involves two important conformers. In this work, employing density functional theory (DFT and handling the solvent effects with the PCM model, the structural parameters, energetic behavior, natural bond orbital analysis (NBO, as well as tautomerism mechanization of the Acamprosate are investigated in several solvents. The conformers of the Keto tautomer are more stable than the corresponding conformers of the Enol tautomer. A strong intramolecular hydrogen bond stabilizes the molecule significantly. Increasing the polarity of the solvent reduces the rate of the tautomerization of the Acamprosate by increasing the Ea of the reaction. A large HOMO-LUMO energy gap for the most stable tautomer implies high stability of the Acamprosate.

  1. A statistical mechanical model for drug release: Investigations on size and porosity dependence

    Science.gov (United States)

    Gomes Filho, Márcio Sampaio; Oliveira, Fernando Albuquerque; Barbosa, Marco Aurélio Alves

    2016-10-01

    A lattice gas model is proposed for investigating the release of drug molecules in capsules covered with semi-permeable membranes. Release patterns in one and two dimensional systems are obtained with Monte Carlo simulations and adjusted to the semi-empirical Weibull distribution function. An analytical solution to the diffusion equation is used to complement and guide simulations in one dimension. Size and porosity dependence analysis was made on the two semi-empirical parameters of the Weibull function, which are related to characteristic time and release mechanism, and our results indicate that a simple scaling law occurs only for systems with almost impermeable membranes, represented in our model by capsules with a single leaking site.

  2. A DFT investigation of structure, spectroscopic properties and tautomerism of the anticonvulsant drug Lyrica

    Science.gov (United States)

    Sadeghzade, Zohre; Beyramabadi, S. Ali; Morsali, Ali

    2015-03-01

    The Lyrica (Pregabalin) is a novel anticonvulsant and neuropathic pain drug, which could exist as four possible conformers. Herein, employing density functional theory (DFT), and handling the solvent effects with the PCM model, the structural parameters, energetic behavior, natural bond orbital analysis (NBO), as well as tautomerism mechanization of the Lyrica are investigated. The L1 (-OH form) is the most stable conformer of the Lyrica, which can be tautomerized to the L5 (-NH form) tautomer. The tautomerism reaction includes an intramolecular-proton transfer, which affects considerably the structural parameters and atomic charges of the L1. The DFT-computed NMR chemical shifts and IR vibrational frequencies are good in agreement with the experimental values, confirming suitability of the optimized geometry for the Lyrica.

  3. Moral disengagement and associated processes in performance-enhancing drug use: a national qualitative investigation.

    Science.gov (United States)

    Boardley, Ian D; Grix, Jonathan; Dewar, Andrew James

    2014-01-01

    This study investigated psychosocial processes associated with avoidance of health- and morality-based deterrents to performance-enhancing drug (PED) use. In-depth semi-structured interviews were conducted with 64 English male bodybuilders with experience of doping. Resultant data were content analysed deductively using definitions for the eight mechanisms of moral disengagement (MD; Bandura, A. (1991). Social cognitive theory of moral thought and action. In W. M. Kurtines & J. L. Gewirtz (Eds.), Handbook of moral behavior and development: Theory research and applications (pp. 71-129). Hillsdale, NJ: Lawrence Erlbaum Associates.), and three further themes from Boardley and Grix (2013. Doping in bodybuilders: A qualitative investigation of facilitative psychosocial processes. Qualitative Research in Sport, Exercise, and Health. Advance online publication, doi 10.1080/2159676X.2013.766809). These analyses evidenced six MD mechanisms, and all three of the themes from Boardley and Grix (2013. Doping in bodybuilders: A qualitative investigation of facilitative psychosocial processes. Qualitative Research in Sport, Exercise, and Health. Advance online publication). Subsequent frequency analyses revealed six of the eight MD mechanisms, and two of the three additional themes, were common across the sample. Overall, the findings suggest MD may help athletes circumvent health- and morality-based deterrents to doping, describe a process linking supplement and PED use and detail how some athletes may actively avoid social censure for doping by only discussing PED use with other PED users from within their training environment.

  4. Statistical investigation of simulated intestinal fluid composition on the equilibrium solubility of biopharmaceutics classification system class II drugs.

    Science.gov (United States)

    Khadra, Ibrahim; Zhou, Zhou; Dunn, Claire; Wilson, Clive G; Halbert, Gavin

    2015-01-25

    A drug's solubility and dissolution behaviour within the gastrointestinal tract is a key property for successful administration by the oral route and one of the key factors in the biopharmaceutics classification system. This property can be determined by investigating drug solubility in human intestinal fluid (HIF) but this is difficult to obtain and highly variable, which has led to the development of multiple simulated intestinal fluid (SIF) recipes. Using a statistical design of experiment (DoE) technique this paper has investigated the effects and interactions on equilibrium drug solubility of seven typical SIF components (sodium taurocholate, lecithin, sodium phosphate, sodium chloride, pH, pancreatin and sodium oleate) within concentration ranges relevant to human intestinal fluid values. A range of poorly soluble drugs with acidic (naproxen, indomethacin, phenytoin, and piroxicam), basic (aprepitant, carvedilol, zafirlukast, tadalafil) or neutral (fenofibrate, griseofulvin, felodipine and probucol) properties have been investigated. The equilibrium solubility results determined are comparable with literature studies of the drugs in either HIF or SIF indicating that the DoE is operating in the correct space. With the exception of pancreatin, all of the factors individually had a statistically significant influence on equilibrium solubility with variations in magnitude of effect between the acidic and basic or neutral compounds and drug specific interactions were evident. Interestingly for the neutral compounds pH was the factor with the second largest solubility effect. Around one third of all the possible factor combinations showed a significant influence on equilibrium solubility with variations in interaction significance and magnitude of effect between the acidic and basic or neutral compounds. The least number of significant media component interactions were noted for the acidic compounds with three and the greatest for the neutral compounds at seven

  5. Pharmacological characterization of a novel investigational antimuscarinic drug, fesoterodine, in vitro and in vivo.

    Science.gov (United States)

    Ney, Peter; Pandita, Raj Kumar; Newgreen, Donald T; Breidenbach, Alexander; Stöhr, Thomas; Andersson, Karl-Erik

    2008-04-01

    To investigate the primary pharmacology of fesoterodine (a novel antimuscarinic drug developed for treating overactive bladder) and SPM 7605 (its active metabolite, considered to be the main pharmacologically active principle of fesoterodine in man) against human muscarinic receptor subtypes, and to investigate in vitro and in vivo functional activity of these agents on the rat bladder compared with existing standard agents. The displacement of radioligand binding by fesoterodine, SPM 7605 and standard agents in membrane preparations of Chinese hamster ovary (CHO) cells expressing the different human muscarinic receptors (M1-M5) was characterized. Agonistic and antagonistic activities were studied using different CHO cell lines stably expressing the human recombinant muscarinic receptor subtypes. The effects of fesoterodine and SPM 7605 on isolated bladder strips contracted by carbachol or electrical field stimulation (EFS) were investigated. In vivo the effects of fesoterodine and SPM 7605 on micturition variables were assessed using continuous cystometry in conscious female Sprague-Dawley rats, and compared to those of oxybutynin and atropine. In vitro SPM 7605 potently inhibited radioligand binding at all five human muscarinic receptor subtypes with equal affinity across all five. Fesoterodine had a similar balanced selectivity profile but was less potent than SPM 7605. Both substances were competitive antagonists of cholinergic agonist-stimulated responses in human M1-M5 cell lines and had a similar potency and selectivity profile to the radioligand-binding studies. In rat bladder strips, fesoterodine and SPM 7605 caused a rightward shift of the concentration-response curve for carbachol with no depression of the maximum, and concentration-dependently reduced contractions induced by EFS. The potency of both drugs was similar to that of atropine and oxybutynin. In the presence of the esterase inhibitor neostigmine, the concentration-response curve of

  6. Synthesis and investigating the magnetic properties of magnetite nanocrystallites for drug delivery

    Science.gov (United States)

    Ansar, Muhammad Zaka; Atiq, Shahid; Riaz, Saira; Naseem, Shahzad; Ramay, Shahid M.; Mahmood, Asif

    2015-07-01

    In recent years, use of magnetic nanoparticles in biomedical applications has increased tremendously. In particular, magnetite (Fe3O4) nanoparticles being highly biocompatible are rated very high due to their potential applications in biomedicines, for instance in anticancer drug delivery. In this work, the Fe3O4 nanoparticles have been synthesized using a novel sol-gel based autocombustion technique. The crystal structure of the Fe3O4 phase was confirmed by the data obtained from X-ray diffraction. Scherrer’s formula was employed to estimate the crystallite size of the Fe3O4 nanoparticles. The structural morphology, investigated by using a scanning electron microscopy (SEM), revealed well-dispersed and uniform sized grains in the sample prepared using enhanced fuel concentration. A vibrating sample magnetometer (VSM) was employed to investigate the magnetic characteristics of the samples which confirmed the superparamagnetic nature of the Fe3O4 samples, essentially required for cancer treatment. These nanoparticles could further be modified and functionalized by suitable polymers to achieve better biocompatibility before being injected into the diseased cells.

  7. Differential scanning calorimetry as a tool to investigate the transfer of anticancer drugs to biomembrane model.

    Science.gov (United States)

    Sarpietro, Maria Grazia; Accolla, Maria Lorena; Celia, Christian; Grattoni, Alessandro; Castelli, Francesco; Fresta, Massimo; Ferrari, Mauro; Paolino, Donatella

    2013-08-01

    Different anticancer drugs clinically approved by international regulatory organizations present poor water solubility and low stability after systemic injection. Their administration requires suitable carriers capable of maximizing therapeutic efficacy. Lipid and polymeric nanotherapeutics, particularly liposomes, are widely used to deliver chemotherapeutics in the clinic. The interaction between chemotherapeutics and biocompatible lipids and polymers can affect their efficacy and play a pivotal role in chemotherapy. Phospholipids are the main components of liposomes and their interactions with therapeutic agents are widely investigated in the pharmaceutical field using differential scanning calorimetry (DSC). In this work, DSC was exploited to investigate the interaction between hydrophobic chemotherapeutics, i.e. docetaxel, tamoxifen and lapatinib, with lipid vesicles. Lipid carriers are prepared using dimyristoylphosphatidylcholine (DMPC), a phosphatidylcholine derivative, showing the same physicochemical features of the main lipids in the biological membranes. DMPC was used as a biological membrane model to evaluate interaction, passage, diffusion, and adsorption of chemotherapeutics. These processes were evaluated through the variation of thermotropic parameters of the biological membrane model. DSC studies were carried out in heating and cooling mode. Results demonstrated a modification of calorimetric curves and this effect is strictly related to the molar fraction and physicochemical features of chemotherapeutics. Furthermore, the interaction between chemotherapeutics and biological membranes affects their internalization and distribution inside tumors and this process depends on gel-liquid crystal transition of phospholipids. DSC results provide suitable information about this effect and can be used as tool to predict further interaction between chemotherapeutics and biological membranes.

  8. Inhibition mechanism exploration of investigational drug TAK-441 as inhibitor against Vismodegib-resistant Smoothened mutant.

    Science.gov (United States)

    Ishii, Tsuyoshi; Shimizu, Yuji; Nakashima, Kosuke; Kondo, Shigeru; Ogawa, Kazumasa; Sasaki, Satoshi; Matsui, Hideki

    2014-01-15

    Hedgehog signaling is a driving force in medulloblastoma and basal cell carcinoma (BCC), making it an attractive therapeutic target. Vismodegib recently received FDA approval for the treatment of inoperable BCC, but a drug-resistant Smoothened (Smo) mutant (D473H) was identified in a clinical study. TAK-441 is a pyrrolo[3,2-c]pyridine-4-one derivative that potently inhibits Hh signal transduction and is currently under investigation in clinical trials. We demonstrated that TAK-441 inhibits reporter activity in D473H-transfected cells with an IC50 of 79nM, while Vismodegib showed an IC50=7100nM. In order to investigate the mode of inhibition, we evaluated the Smo inhibitors with three different binding assays, such as [(3)H]-TAK-441 membrane binding assay, affinity selection-MS detection assay, and bodipy-cylopamine whole cell assay. In three different assays, Vismodegib and cyclopamine showed lower affinity for the D473H mutant in comparison with wild-type Smo. On the other hand, TAK-441 showed almost equal binding affinity for the D473H mutant compared with wild-type Smo in the binding assays, although TAK-441 binds to the same binding site as two other well-known inhibitors. These in vitro findings suggest that TAK-441 has the potential for clinical use in cancers that are dependent on Hedgehog signaling, including wild-type tumors and Vismodegib-resistant D473H mutants.

  9. Investigational drugs for the management of Huntington's disease: are we there yet?

    Science.gov (United States)

    Kulkarni, Pushkar; Saxena, Uday

    2014-12-01

    Huntington's disease is a hereditary neurodegenerative disease. It is designated as a rare disease in the US, which means there are disease were not designed specifically for it but developed for other diseases. Presently, two classes of drugs are being developed; those that provide symptomatic relief and those that may modify course of the disease. This review is focused on seven selected drugs currently in clinical testing and describes their progress. Five of the seven drugs that are reviewed here, can be categorized as 'symptomatic' drugs, and, selisistat and PBT-2 are amongst the ones that would qualify as 'disease modifying' drugs. The authors believe that the future treatment paradigm for this disease is best met by using a disease-modifying drug that can be administered together with symptomatic drugs. Towards that end, it is important for the industry to focus on disease-modifying drugs by targeting unique pathways and targets. Furthermore, they propose that neuroprotective drugs, that is, drugs that directly work by preserving neuronal health and function is an opportunity for such disease-modifying drugs.

  10. [Investigation of antimicrobial and antibiofilm effects of some preservatives used in drugs, cosmetics and food products].

    Science.gov (United States)

    Güven, Nihal; Kaynak Onurdağ, Fatma

    2014-01-01

    was also effective against S.epidermidis. However, in our study it was determined that preservatives were not effective against biofilm forms even if the inoculum was lower, equal to or higher than the inocula of the planktonic forms. The data obtained from this study indicated that preservatives used to prevent microbial contamination in pharmaceutical, cosmetic and food products, are not effective against biofilm forms of the microorganisms. This study is thought to be a guide for further studies to be held in the investigation of antimicrobial and antibiofilm effects of preservatives used in drugs, cosmetics and food industry.

  11. Investigation of Direct Causes of Drug Relapse and Abstainers' Demands in a Compulsive Detoxification Center in Wuhan City of China

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    To identify the direct causes of drug relapse and abstainers' demand,and to develop programs for the prevention of dmg relapse.Methods Abstainers in a Compulsive Detoxification Center in Wuhan City,capital of Hubei Province were randomly selected. An investigation on the direct causes of drug relapse and abstainers' demands was conducted with multiple-choice questionnaires and face to face interviews. Data were analyzed with SPSS 12.0.Results The direct causes leading to drug relapse included:temptation to use drug again by themselves or by their drug mates,seeking pleasure and ecstasy from drug use,relatively well off living,mental stress,irritation,demoralization,family conflicts,unemployment,feeling distrusted by the family,lack of care and love from the family,and discrimination by others.abstainers' demands after detoxification and returning to the society included:care and support from the family,employment assistance,changing living environment,understanding by others,support from the society,and keeping far away from drugs.Conclusions Environmental factors are the direct causes of drug relapse,and negative irritation is its predisposing causes. Leaving former residence,more care and help given by both the family and the society and raising their overall quality of life are the demands of abstainers.

  12. Proteomics Investigations of Drug-Induced Hepatotoxicity in HepG2 Cells

    OpenAIRE

    Van Summeren, Anke; Renes, Johan; Bouwman, Freek G.; Noben, Jean-Paul; van Delft, Joost H. M.; Kleinjans, Jos C.S.; Mariman, Edwin C. M.

    2011-01-01

    Unexpected hepatotoxicity is one of the major reasons of drugs failing in clinical trials. This emphasizes the need for new screening methods that address toxicological hazards early in the drug discovery process. Here, proteomics techniques were used to gain further insight into the mechanistic processes of the hepatotoxic compounds. Drug-induced hepatotoxicity is mainly divided in hepatic steatosis, cholestasis, or necrosis. For each class, a compound was selected, respectively amiodarone, ...

  13. Investigation of Plasma Treatment on Micro-Injection Moulded Microneedle for Drug Delivery.

    Science.gov (United States)

    Nair, Karthik; Whiteside, Benjamin; Grant, Colin; Patel, Rajnikant; Tuinea-Bobe, Cristina; Norris, Keith; Paradkar, Anant

    2015-10-30

    Plasma technology has been widely used to increase the surface energy of the polymer surfaces for many industrial applications; in particular to increase in wettability. The present work was carried out to investigate how surface modification using plasma treatment modifies the surface energy of micro-injection moulded microneedles and its influence on drug delivery. Microneedles of polyether ether ketone and polycarbonate and have been manufactured using micro-injection moulding and samples from each production batch have been subsequently subjected to a range of plasma treatment. These samples were coated with bovine serum albumin to study the protein adsorption on these treated polymer surfaces. Sample surfaces structures, before and after treatment, were studied using atomic force microscope and surface energies have been obtained using contact angle measurement and calculated using the Owens-Wendt theory. Adsorption performance of bovine serum albumin and release kinetics for each sample set was assessed using a Franz diffusion cell. Results indicate that plasma treatment significantly increases the surface energy and roughness of the microneedles resulting in better adsorption and release of BSA.

  14. Investigation of Plasma Treatment on Micro-Injection Moulded Microneedle for Drug Delivery

    Science.gov (United States)

    Nair, Karthik; Whiteside, Benjamin; Grant, Colin; Patel, Rajnikant; Tuinea-Bobe, Cristina; Norris, Keith; Paradkar, Anant

    2015-01-01

    Plasma technology has been widely used to increase the surface energy of the polymer surfaces for many industrial applications; in particular to increase in wettability. The present work was carried out to investigate how surface modification using plasma treatment modifies the surface energy of micro-injection moulded microneedles and its influence on drug delivery. Microneedles of polyether ether ketone and polycarbonate and have been manufactured using micro-injection moulding and samples from each production batch have been subsequently subjected to a range of plasma treatment. These samples were coated with bovine serum albumin to study the protein adsorption on these treated polymer surfaces. Sample surfaces structures, before and after treatment, were studied using atomic force microscope and surface energies have been obtained using contact angle measurement and calculated using the Owens-Wendt theory. Adsorption performance of bovine serum albumin and release kinetics for each sample set was assessed using a Franz diffusion cell. Results indicate that plasma treatment significantly increases the surface energy and roughness of the microneedles resulting in better adsorption and release of BSA. PMID:26529005

  15. Clinical research: business opportunities for pharmacy-based investigational drug services.

    Science.gov (United States)

    Marnocha, R M

    1999-02-01

    The application by an academic health center of business principles to the conduct of clinical research is described. Re-engineering of the infrastructure for clinical research at the University of Wisconsin and University of Wisconsin Hospital and Clinics began in 1990 with the creation of the Center for Clinical Trials (CCT) and the restructuring of the investigational drug services (IDS). Strategies to further improve the institution's clinical research activities have been continually assessed and most recently have centered on the adaptation of a business philosophy within the institution's multidisciplinary research infrastructure. Toward that end, the CCT and IDS have introduced basic business principles into operational activities. Four basic business concepts have been implemented: viewing the research protocol as a commodity, seeking payment for services rendered, tracking investments, and assessing performance. It is proposed that incorporation of these basic business concepts is not only compatible with the infrastructure for clinical research but beneficial to that infrastructure. The adaptation of a business mindset is likely to enable an academic health center to reach its clinical research goals.

  16. Investigation of Plasma Treatment on Micro-Injection Moulded Microneedle for Drug Delivery

    Directory of Open Access Journals (Sweden)

    Karthik Nair

    2015-10-01

    Full Text Available Plasma technology has been widely used to increase the surface energy of the polymer surfaces for many industrial applications; in particular to increase in wettability. The present work was carried out to investigate how surface modification using plasma treatment modifies the surface energy of micro-injection moulded microneedles and its influence on drug delivery. Microneedles of polyether ether ketone and polycarbonate and have been manufactured using micro-injection moulding and samples from each production batch have been subsequently subjected to a range of plasma treatment. These samples were coated with bovine serum albumin to study the protein adsorption on these treated polymer surfaces. Sample surfaces structures, before and after treatment, were studied using atomic force microscope and surface energies have been obtained using contact angle measurement and calculated using the Owens-Wendt theory. Adsorption performance of bovine serum albumin and release kinetics for each sample set was assessed using a Franz diffusion cell. Results indicate that plasma treatment significantly increases the surface energy and roughness of the microneedles resulting in better adsorption and release of BSA.

  17. An investigation of effects of modification processes on physical properties and mechanism of drug release for sustaining drug release from modified rice.

    Science.gov (United States)

    Ngo, Vuong Duy; Luu, Thinh Duc; Van Vo, Toi; Tran, Van-Thanh; Duan, Wei; Tran, Phuong Ha-Lien; Tran, Thao Truong-Dinh

    2016-10-01

    The aim of this study was to investigate the effect of modification processes on physical properties and explain the mechanism of sustained drug release from modified rice (MR). Various types of Vietnamese rice were introduced in the study as the matrices of sustained release dosage form. Rice was thermally modified in water for a determined temperature at different times with a simple process. Then tablets containing MR and isradipine, the model drug, were prepared to investigate the capability of sustained drug release. Scanning electron microscopy (SEM) was used to determine different morphologies between MR formulations. Flow property of MR was analyzed by Hausner ratio and Carr's indices. The dissolution rate and swelling/erosion behaviors of tablets were evaluated at pH 1.2 and pH6.8 at 37±0.5°C. The matrix tablet containing MR showed a sustained release as compared to the control. The SEM analyses and swelling/erosion studies indicated that the morphology as well as swelling/erosion rate of MR were modulated by modification time, drying method and incubation. It was found that the modification process was crucial because it could highly affect the granule morphologies and hence, leading to the change of flowability and swelling/erosion capacity for sustained release of drug.

  18. The effect of federal and state off-label marketing investigations on drug prescribing: The case of olanzapine.

    Science.gov (United States)

    Wang, Bo; Studdert, David M; Sarpatwari, Ameet; Franklin, Jessica M; Landon, Joan; Kesselheim, Aaron S

    2017-01-01

    In the past decade, the federal government has frequently investigated and prosecuted pharmaceutical manufacturers for illegal promotion of drugs for indications not approved by the Food and Drug Administration (FDA) ("off-label" uses). State governments can choose to coordinate with the federal investigation, or pursue their own independent state investigations. One of the largest-ever off-label prosecutions relates to the atypical antipsychotic drug olanzapine (Zyprexa). In a series of settlements between 2008 and 2010, Eli Lilly paid $1.4 billion to the federal government and over $290 million to state governments. We examined the effect of these settlements on off-label prescribing of this medication, taking advantage of geographical differences in states' involvement in the investigations and the timing of the settlements. However, we did not find a reduction in off-label prescribing; rather, there were no prescribing changes among states that joined the federal investigation, those that pursued independent state investigations, and states that pursued no investigations at all. Since the settlements of state investigations of off-label prescribing do not appear to significantly impact prescribing rates, policymakers should consider alternate ways of reducing the prevalence of non-evidence-based off-label use to complement their ongoing investigations.

  19. Systems pharmacology to investigate the interaction of berberine and other drugs in treating polycystic ovary syndrome

    Science.gov (United States)

    Wang, Yu; Fu, Xin; Xu, Jing; Wang, Qiuhong; Kuang, Haixue

    2016-01-01

    Polycystic ovary syndrome (PCOS) is a common multifactorial endocrine disorder among women of childbearing age. PCOS has various and heterogeneous clinical features apart from its indefinite pathogenesis and mechanism. Clinical drugs for PCOS are multifarious because it only treats separate symptoms. Berberine is an isoquinoline plant alkaloid with numerous biological activities, and it was testified to improve some diseases related to PCOS in animal models and in humans. Systems pharmacology was utilized to predict the potential targets of berberine related to PCOS and the potential drug-drug interaction base on the disease network. In conclusion, berberine is a promising polypharmacological drug for treating PCOS, and for enhancing the efficacy of clinical drugs. PMID:27306862

  20. An investigation into the precedents of modern drug treatment in psychiatry.

    Science.gov (United States)

    Moncrieff, J

    1999-12-01

    This paper examines some of the factors associated with the introduction of a range of new drug treatments into psychiatry in the 1950s and 1960s. The nature of psychiatry in the United Kingdom in preceding decades is examined and a continuous emphasis on biological explanations and treatments of mental disorder is revealed. Physical treatment procedures such as insulin coma therapy and shock treatment received most attention. Older drug treatments, although widely used, excited little interest during this time. The new drug treatments by contrast received much attention and began to be regarded as having specific effects on different mental disorders. It is suggested that a combination of long-standing professional concerns and commercial factors helped to account for the rapid acceptance and employment of the new drugs. In turn, these drugs helped to strenghten the hegemony of the medical approach to mental illness.

  1. In vivo investigation of temporal effects and drug delivery induced by transdermal microneedles with optical coherence tomography

    Science.gov (United States)

    Tsai, Meng-Tsan; Lee, I-Chi; Lee, Zhung-Fu; Liu, Hao-Li; Wang, Chun-Chieh; Choia, Yo-Chun; Chou, Hsin-Yi; Lee, Jiann-Der

    2016-01-01

    Transdermal drug-delivery systems (TDDS) have been a growing field in drug delivery because of their advantages over parenteral and oral administration. Recent studies illustrate that microneedles (MNs) can effectively penetrate through the stratum corneum barrier to facilitate drug delivery. However, the temporal effects on skin and drug diffusion are difficult to investigate in vivo. In this study, we used optical coherence tomography (OCT) to observe the process by which MNs dissolve and to investigate the temporal effects on mouse skin induced by MNs, including the morphological and vascular changes. Moreover, the recovery process of the skin was observed with OCT. Additionally, we proposed a method to observe drug delivery by estimation of cross-correlation relationship between sequential 2D OCT images obtained at the same location, reflecting the variation in the backscattered intensity due to the diffusion of the rhodamine molecules encapsulated in MNs. Our observations supported the hypothesis that the temporal effects on skin due to MNs, the dissolution of MNs, and the drug diffusion process can be quantitatively evaluated with OCT. The results showed that OCT can be a potential tool for in vivo monitoring of effects and outcomes when MNs are used as a TDDS. PMID:27231627

  2. Lyophilized silica lipid hybrid (SLH) carriers for poorly water-soluble drugs: physicochemical and in vitro pharmaceutical investigations.

    Science.gov (United States)

    Yasmin, Rokhsana; Tan, Angel; Bremmell, Kristen E; Prestidge, Clive A

    2014-09-01

    Lyophilization was investigated to produce a powdery silica-lipid hybrid (SLH) carrier for oral delivery of poorly water-soluble drugs. The silica to lipid ratio, incorporation of cryoprotectant, and lipid loading level were investigated as performance indicators for lyophilized SLH carriers. Celecoxib, a nonsteroidal anti-inflammatory drug, was used as the model poorly soluble moiety to attain desirable physicochemical and in vitro drug solubilization properties. Scanning electron microscopy and confocal fluorescence imaging verified a nanoporous, homogenous internal matrix structures of the lyophilized SLH particles, prepared from submicron triglyceride emulsions and stabilized by porous silica nanoparticles (Aerosil 380), similar to spray-dried SLH. 20-50 wt % of silica in the formulation have shown to produce nonoily SLH agglomerates with complete lipid encapsulation. The incorporation of a cryoprotectant prevented irreversible aggregation of the silica-stabilized droplets during lyophilization, thereby readily redispersing in water to form micrometre-sized particles (drug solubilization than the pure drug under nondigesting and digesting conditions, respectively. The feasibility of lyophilization for producing nanostructured SLH formulations with desirable lipid loading and drug solubilization properties for enhanced oral delivery of poorly water-soluble therapeutics is confirmed. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  3. An investigation of effects of modification processes on physical properties and mechanism of drug release for sustaining drug release from modified rice

    Energy Technology Data Exchange (ETDEWEB)

    Ngo, Vuong Duy; Luu, Thinh Duc; Van Vo, Toi [Pharmaceutical Engineering Laboratory, Biomedical Engineering Department, International University, Vietnam National University, Ho Chi Minh City (Viet Nam); Tran, Van-Thanh [Faculty of Pharmacy, University of Medicine and Pharmacy, Ho Chi Minh City (Viet Nam); Duan, Wei [School of Medicine, Deakin University, Pigdons Road, Waurn Ponds, Victoria (Australia); Tran, Phuong Ha-Lien, E-mail: phuong.tran1@deakin.edu.au [School of Medicine, Deakin University, Pigdons Road, Waurn Ponds, Victoria (Australia); Tran, Thao Truong-Dinh, E-mail: ttdthao@hcmiu.edu.vn [Pharmaceutical Engineering Laboratory, Biomedical Engineering Department, International University, Vietnam National University, Ho Chi Minh City (Viet Nam)

    2016-10-01

    The aim of this study was to investigate the effect of modification processes on physical properties and explain the mechanism of sustained drug release from modified rice (MR). Various types of Vietnamese rice were introduced in the study as the matrices of sustained release dosage form. Rice was thermally modified in water for a determined temperature at different times with a simple process. Then tablets containing MR and isradipine, the model drug, were prepared to investigate the capability of sustained drug release. Scanning electron microscopy (SEM) was used to determine different morphologies between MR formulations. Flow property of MR was analyzed by Hausner ratio and Carr's indices. The dissolution rate and swelling/erosion behaviors of tablets were evaluated at pH 1.2 and pH 6.8 at 37 ± 0.5 °C. The matrix tablet containing MR showed a sustained release as compared to the control. The SEM analyses and swelling/erosion studies indicated that the morphology as well as swelling/erosion rate of MR were modulated by modification time, drying method and incubation. It was found that the modification process was crucial because it could highly affect the granule morphologies and hence, leading to the change of flowability and swelling/erosion capacity for sustained release of drug. - Highlights: • Modification process affected granule morphologies and flowability of modified rice. • Modification process affected swelling/erosion capacity for drug sustained release. • Freeze-drying could decrease the erosion as well as increase the swelling rate.

  4. Methodologies and Application of New Target Identification, Drug Action Mechanism Investigation and New Molecular Entity Discovery

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    @@ The group, headed by Prof.JIANG Hualiang with the CAS Shanghai Institute of Materia Medica, has been centering on the basic research of pharmaceutical science, including identifying new targets, studying new drug action mechanisms and discovering new drug candidates.On the basis of new methodology development, an effective multi-disciplinary research platform for drug research and discovery has been established through the integration of different disciplines of computational chemistry, organic synthesis, molecular and cellular biology.A bunch of creative results have been achieved in these areas.

  5. New investigation of distribution imaging and content uniformity of very low dose drugs using hot-melt extrusion method.

    Science.gov (United States)

    Park, Jun-Bom; Kang, Chin-Yang; Kang, Wie-Soo; Choi, Han-Gon; Han, Hyo-Kyung; Lee, Beom-Jin

    2013-12-31

    The content uniformity of low dose drugs in dosage forms is very important for quality assurance. The aim of this study was to prepare uniformly and homogeneously distributed dosage forms of very low-dose drugs using twin screw hot-melt extrusion (HME) and to investigate the distribution of drugs using instrumental analyses. For the feasibility of HME method, a very low amount of coumarin-6, a fluorescent dye, was used to visualize distribution images using confocal laser scanning microscope (CLSM). Limaprost, tamsulosin and glimepiride were then used as low-dose model drugs to study the applicability of HME for content uniformity and distribution behaviors. Hydrophilic thermosensitive polymers with low melting point, such as Poloxamer188 and polyethylene glycol (PEG) 6000, were chosen as carriers. The melt extrusion was carried out around 50°C, at which both carriers were easily dissolved but model drugs remained in solid form. The physicochemical properties of the hot-melt extrudates, including differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and Fourier transform infrared spectroscopy (FT-IR), were measured. Content uniformity of the drugs was also checked by HPLC. CLSM imaging showed that model drugs were well distributed throughout the hot-melt extrudate, giving better content uniformity with low batch-to-batch variations compared with simple physical mixtures. DSC, PXRD and FT-IR data showed that there was no interaction or interference between model drugs and thermosensitive polymers. The current HME methods could be used to prepare uniformly distributed and reproducible solid dosage forms containing very low dose drugs for further pharmaceutical applications.

  6. Genealogical analysis as a new approach for the investigation of drug intolerance heritability.

    Science.gov (United States)

    Tremblay, Marc; Bouhali, Tarek; Gaudet, Daniel; Brisson, Diane

    2014-07-01

    Genealogical analysis has proven a useful method to understand the origins and frequencies of hereditary diseases in many populations. However, this type of analysis has not yet been used for the investigation of drug intolerance among patients suffering from inherited disorders. This study aims to do so, using data from familial hypercholesterolemia (FH) patients receiving high doses of statins. The objective is to measure and compare various genealogical parameters that could shed light on the origins and heritability of muscular intolerance to statins using FH as a model. Analysis was performed on 224 genealogies from 112 FH subjects carrying either the low-density lipoprotein receptor (LDLR) prom_e1 deletion>15 kb (n=28) or c.259T>G (p.Trp87Gly) (n=84) mutations and 112 non-FH controls. Number of ancestors, geographical origins and genetic contribution of founders, inbreeding and kinship coefficients were calculated using the S-Plus-based GENLIB software package. For both mutations, repeated occurrences of the same ancestors are more frequent among the carriers' genealogies than among the controls', but no difference was observed between tolerant and intolerant subjects. Founders who may have introduced both mutations in the population appear with approximately the same frequencies in all genealogies. Kinship coefficients are higher among carriers, with no difference according to statins tolerance. Inbreeding coefficients are slightly lower among >15-kb deletion carriers than among c.259 T>G carriers, but the differences between tolerants and intolerants are not significant. These findings suggest that although muscular intolerance to statins shows a family aggregation, it is not transmitted through the same Mendelian pattern as LDLR mutations.

  7. Enantioselective Supramolecular Carriers for Nucleoside Drugs. A Thermodynamic and Kinetic Gas Phase Investigation

    Science.gov (United States)

    Fraschetti, Caterina; Filippi, Antonello; Crestoni, Maria Elisa; Villani, Claudio; Roselli, Graziella; Mortera, Stefano Levi; Speranza, Maurizio

    2012-10-01

    The enantioselective interactions between chiral tetra-amidic receptors and nucleosides have been investigated by the ESI-IT-MS and ESI-FT-ICR-MS methodologies. Configurational effects on the CID fragmentation of diastereomeric [ M H 2 •H•A] + aggregates (A = 2'-deoxycytidine dC, citarabine ( ara-C) were found to be mostly offset by isotope effect in [ S X 2 •H•A] + (X = H, D) differently from the results obtained on the analogues (A = cytidine C and gemcitabine G). This result points the involvement of two different nucleoside/tetraamide isoforms. The structural differences of the [ M H 2 •H•A] + (A = C and G) complexes vs. the [ M H 2 •H•A] + ( dC and ara-C) ones is fully confirmed by the kinetics of their uptake of the 2-aminobutane enantiomers, measured by FT-ICR mass spectrometry. Indeed, uptake of the 2-aminobutane enantiomers by [ M H n •H•A] + (n = 1,2; A = dC and ara-C) complexes is reversible, while that by [ M H n •H•A] + (n = 1,2; A = C and G) is not. The most encouraging result concerning the measured fragmentation and kinetic differences between C and ara-C, that are just epimers, indicates the possibility to subtly modulate the non-covalent drug/receptor interactions, through the electronic properties of the 2'-substituent on the nucleoside furanose ring, and furthermore on its three-dimensional position.

  8. Research Costs Investigated: A Study Into the Budgets of Dutch Publicly Funded Drug-Related Research.

    Science.gov (United States)

    van Asselt, Thea; Ramaekers, Bram; Corro Ramos, Isaac; Joore, Manuela; Al, Maiwenn; Lesman-Leegte, Ivonne; Postma, Maarten; Vemer, Pepijn; Feenstra, Talitha

    2017-09-20

    The costs of performing research are an important input in value of information (VOI) analyses but are difficult to assess. The aim of this study was to investigate the costs of research, serving two purposes: (1) estimating research costs for use in VOI analyses; and (2) developing a costing tool to support reviewers of grant proposals in assessing whether the proposed budget is realistic. For granted study proposals from the Netherlands Organization for Health Research and Development (ZonMw), type of study, potential cost drivers, proposed budget, and general characteristics were extracted. Regression analysis was conducted in an attempt to generate a 'predicted budget' for certain combinations of cost drivers, for implementation in the costing tool. Of 133 drug-related research grant proposals, 74 were included for complete data extraction. Because an association between cost drivers and budgets was not confirmed, we could not generate a predicted budget based on regression analysis, but only historic reference budgets given certain study characteristics. The costing tool was designed accordingly, i.e. with given selection criteria the tool returns the range of budgets in comparable studies. This range can be used in VOI analysis to estimate whether the expected net benefit of sampling will be positive to decide upon the net value of future research. The absence of association between study characteristics and budgets may indicate inconsistencies in the budgeting or granting process. Nonetheless, the tool generates useful information on historical budgets, and the option to formally relate VOI to budgets. To our knowledge, this is the first attempt at creating such a tool, which can be complemented with new studies being granted, enlarging the underlying database and keeping estimates up to date.

  9. Development and investigation of gastro retentive dosage form of weakly basic drug

    Directory of Open Access Journals (Sweden)

    Shah Samip

    2010-01-01

    Full Text Available The release of drug substance from controlled-release dosage forms is often pH-dependent since most drugs are either weak acids or weak bases. A system that permits the drug release to be changed freely while maintaining pH-independent drug release (model drug was Domperidone was developed. Powder mixture of drug and HPMC K4M, eudragit L100, sodium bicarbonate (as gas-generating agent and other excipients were mixed and directly compressed using single-punch tablet compression machine. It was found that sodium bicarbonate reacts with HCl and produce carbon dioxide which creates pores in tablet and elevates swelling by wetting the polymer. So it helps in maintaining the buoyancy. The release rate could be modified by varying the polymer ratio. The prepared tablets were evaluated for general appearance, content uniformity, hardness, friability, buoyancy, in vitro drug release and in vivo studies. The best formulation (D 1 was selected based on in vitro characteristics and was used in vivo radiographic studies by incorporating BaSO 4 . These studies revealed that the tablets remained in the stomach for 250±30 min in fasted rabbits and indicated that gastric retention time was increased by the floating principle, which was considered desirable for the absorption window drugs. The linear regression analysis and model fitting showed that all these formulations followed Higuchi model, which had a higher value of correlation coefficient (r. The scanning electron microscopy images of the tablet (D 1 formulation were taken before and after dissolution and images showed that the drug was released from matrix by diffusion mechanism. Stability studies of all formulations were carried out at elevated temperature and humidity conditions of 40±2 o C/75±5% RH and a control sample was placed at an ambient condition for 12 months. It was found that there was no significant change in buoyancy property as well as in drug content from initial drug content of all

  10. Systematic investigation of different formulations for drug delivery through the human nail plate "in vitro"

    OpenAIRE

    Vejnoviċ, Ivana

    2010-01-01

    Human nails do not have only protective and decorative role, but can also be considered as an alternative pathway for drug delivery, especially in nail diseases such as onychomycosis or psoriasis. These nail diseases are widely spread in the population, particularly among elderly and immunocompromised patients. Oral therapies are accompanied by systemic side effects and drug interactions, while topical therapies are limited by the low permeation rate through the nail plate. For the successful...

  11. Systematic investigation of different formulations for drug delivery through the human nail plate "in vitro"

    OpenAIRE

    Vejnoviċ, Ivana

    2010-01-01

    Human nails do not have only protective and decorative role, but can also be considered as an alternative pathway for drug delivery, especially in nail diseases such as onychomycosis or psoriasis. These nail diseases are widely spread in the population, particularly among elderly and immunocompromised patients. Oral therapies are accompanied by systemic side effects and drug interactions, while topical therapies are limited by the low permeation rate through the nail plate. For the successful...

  12. Investigation of release pattern of a drug with low solubility through asymmetric membrane capsules

    Directory of Open Access Journals (Sweden)

    P K Sahoo

    2013-01-01

    Full Text Available Asymmetric membrane capsules are a type of osmotic drug delivery systems. They are nondisintegrating capsules, which utilize osmotic pressure to drive the drug outwards for controlled delivery. Preceded by systems such as elementary osmotic pump, controlled porosity osmotic pump, single composition osmotic tablet this system has the advantage of simple and easy fabrication as it obviates the necessity of drilling an orifice into the drug delivery system. Moreover; it seems to be a low-cost alternative. The cellulose acetate capsule shell, on coming in contact with the aqueous medium shows in situ pore formation due to leaching of pore formers, which have been incorporated into the shell forming solution. Until date, a number of osmotic agents to the likes of sodium chloride, mannitol has been used to build up osmotic pressure inside the cell. The system is endowed with high water flux, which is a plus point for delivery of poorly soluble drugs like cephalexin in terms of increasing release rates. Studies envisaged in this research include the effect of different concentrations of different pore formers on in vitro drug release as well as the effect of modification of inner contents of the capsule. The system was successful in producing a gradual release of drug for 12 h.

  13. A systems-based mathematical modelling framework for investigating the effect of drugs on solid tumours

    Directory of Open Access Journals (Sweden)

    Liu Cong

    2011-12-01

    Full Text Available Abstract Background Elucidating the effects of drugs on solid tumours is a highly challenging multi-level problem, since this involves many complexities associated with transport and cellular response, which in turn is characterized by highly non-linear chemical signal transduction. Appropriate systems frameworks are needed to seriously address the sources of these complexities, especially from the cellular side. Results We develop a skeletal modelling framework incorporating interstitial drug transport, intracellular signal processing and cell population descriptions. The descriptions aim to appropriately capture the nature of information flow. The model is deliberately formulated to start with simple intracellular descriptions so that additional features can be incorporated in a modular fashion. Two kinds of intracellular signalling modules which describe the drug effect were considered, one a monostable switch and the other a bistable switch. Analysis of our model revealed how different drug stimuli can lead to cell killing in the tumour. Interestingly both modules considered exhibited similar trends. The effects of important parameters were also studied. Conclusions We have created a predictive systems platform integrating drug transport and cellular response which can be systematically augmented to include additional layers of cellular complexity. Our results indicate that intracellular signalling models which are qualitatively different can give rise to similar behaviour to simple (and typical stimuli, and that validating intracellular descriptions must be performed with care by considering a variety of drug stimuli.

  14. Investigating the Effects of Loading Factors on the In Vitro Pharmaceutical Performance of Mesoporous Materials as Drug Carriers for Ibuprofen

    Directory of Open Access Journals (Sweden)

    Junmin Lai

    2017-02-01

    Full Text Available The aim of the study was to investigate the effects of the loading factors, i.e., the initial drug loading concentration and the ratio of the drug to carriers, on the in vitro pharmaceutical performance of drug-loaded mesoporous systems. Ibuprofen (IBU was used as a model drug, and two non-ordered mesoporous materials of commercial silica Syloid® 244FP (S244FP and Neusilin® US2 (NS2 were selected in the study. The IBU-loaded mesoporous samples were prepared by a solvent immersion method with a rotary evaporation drying technique and characterized by polarized light microscopy (PLM, Fourier transform infrared (FTIR spectroscopy, X-ray powder diffraction (XRPD and differential scanning calorimetry (DSC. Dissolution experiments were performed in simulated gastric media at 37 °C under non-sink conditions. The concentration of IBU in solution was determined by HPLC. The study showed that the dissolution rate of IBU can be improved significantly using the mesoporous S224FP carriers due to the conversion of crystalline IBU into the amorphous form. Both of the loading factors affected the IBU dissolution kinetics. Due to the molecular interaction between the IBU and NS2 carriers, the loading factors had little effects on the drug release kinetics with incomplete drug desorption recovery and insignificant dissolution enhancement. Care and extensive evaluation must therefore be taken when mesoporous materials are chosen as carrier delivery systems.

  15. Induced circular dichroism as a tool to investigate the binding of drugs to carrier proteins: Classic approaches and new trends.

    Science.gov (United States)

    Tedesco, Daniele; Bertucci, Carlo

    2015-09-10

    Induced circular dichroism (ICD) is a spectroscopic phenomenon that provides versatile and useful methods for characterizing the structural and dynamic properties of the binding of drugs to target proteins. The understanding of biorecognition processes at the molecular level is essential to discover and validate new pharmacological targets, and to design and develop new potent and selective drugs. The present article reviews the main applications of ICD to drug binding studies on serum carrier proteins, going from the classic approaches for the derivation of drug binding parameters and the identification of binding sites, to an overview of the emerging trends for the characterization of binding modes by means of quantum chemical (QC) techniques. The advantages and limits of the ICD methods for the determination of binding parameters are critically reviewed; the capability to investigate the binding interactions of drugs and metabolites to their target proteins is also underlined, as well as the possibility of characterizing the binding sites to obtain a complete picture of the binding mechanism and dynamics. The new applications of ICD methods to identify stereoselective binding modes of drug/protein complexes are then reviewed with relevant examples. The combined application of experimental ICD spectroscopy and QC calculations is shown to identify qualitatively the bound conformations of ligands to target proteins even in the absence of a detailed structure of the binding sites, either obtained from experimental X-ray crystallography and NMR measurements or from computational models of the complex. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Analgesic drug consumption increases after knee arthroplasty: a pharmacoepidemiological study investigating postoperative pain.

    Science.gov (United States)

    Fuzier, Régis; Serres, Isabelle; Bourrel, Robert; Palmaro, Aurore; Montastruc, Jean-Louis; Lapeyre-Mestre, Maryse

    2014-07-01

    Knee arthroplasty remains the gold standard in the treatment of severe osteoarthritis. Chronic postoperative pain has been reported with a prevalence ranging from 15% to 47%. The aim of this study was to compare analgesic drug consumption before and after surgery as an indicator of pain after knee surgery. A pharmacoepidemiological method comparing analgesics and antineuropathic issues 1 year before and 1 year after surgery was used. All patients who underwent knee arthroplasty in the Midi-Pyrenees region (2.5 million inhabitants) were identified through the Health Insurance System Database. Increase of drug issues (all analgesics, antineuropathic drugs, strong opioids) was calculated and compared between several periods surrounding the surgery (12 months, 2 months, and 10 months before and after the knee arthroplasty). A multivariate logistic regression model was used to identify factors associated with chronic postoperative pain. The study included 1939 patients. An increase in analgesic, antineuropathic, and opioid drug consumption was observed the year after the surgery in 47.3%, 8.6%, and 5.6% of patients, respectively. Multivariate analysis found a significant association between type of surgery (total knee vs unicompartmental arthroplasty) and analgesic consumption 1 year after surgery, and between preoperative pain and psychiatric vulnerability and increase in neuropathic drug dispensing. Conversely, older age was considered as a protective factor. This study revealed that an increase in the issue of different analgesic drugs is present in half of patients 1 year after knee arthroplasty. Several associated factors of drug consumption (preoperative pain, type of surgery, and psychiatric disorder) were identified.

  17. Investigation of Drug-Polymer Compatibility Using Chemometric-Assisted UV-Spectrophotometry.

    Science.gov (United States)

    Mohamed, Amir Ibrahim; Abd-Motagaly, Amr Mohamed Elsayed; Ahmed, Osama A A; Amin, Suzan; Mohamed Ali, Alaa Ibrahim

    2017-01-16

    A simple chemometric-assisted UV-spectrophotometric method was used to study the compatibility of clindamycin hydrochloride (HC1) with two commonly used natural controlled-release polymers, alginate (Ag) and chitosan (Ch). Standard mixtures containing 1:1, 1:2, and 1:0.5 w/w drug-polymer ratios were prepared and UV scanned. A calibration model was developed with partial least square (PLS) regression analysis for each polymer separately. Then, test mixtures containing 1:1 w/w drug-polymer ratios with different sets of drug concentrations were prepared. These were UV scanned initially and after three and seven days of storage at 25 °C. Using the calibration model, the drug recovery percent was estimated and a decrease in concentration of 10% or more from initial concentration was considered to indicate instability. PLS models with PC3 (for Ag) and PC2 (for Ch) showed a good correlation between actual and found values with root mean square error of cross validation (RMSECV) of 0.00284 and 0.01228, and calibration coefficient (R²) values of 0.996 and 0.942, respectively. The average drug recovery percent after three and seven days was 98.1 ± 2.9 and 95.4 ± 4.0 (for Ag), and 97.3 ± 2.1 and 91.4 ± 3.8 (for Ch), which suggests more drug compatibility with an Ag than a Ch polymer. Conventional techniques including DSC, XRD, FTIR, and in vitro minimum inhibitory concentration (MIC) for (1:1) drug-polymer mixtures were also performed to confirm clindamycin compatibility with Ag and Ch polymers.

  18. Investigation into the prevalence of coccidiosis and maduramycin drug resistance in chickens in China.

    Science.gov (United States)

    Zhang, Jian Jun; Wang, Li Xia; Ruan, Wen Ke; An, Jian

    2013-01-16

    Coccidiosis is a parasitic disease that affects the poultry industry worldwide, having major economic impacts on poultry by reducing performance and decreasing productivity. This disease not only hinders the growth of chickens but also facilitates other epidemic diseases. Coccidiosis is mainly controlled by prophylactic coccidiostats administrated in the feed. However, the extensive use of these drugs has resulted in the development of drug resistance by Eimeria spp., which causes coccidiosis. The aim of the survey was to acquire data on the prevalence of coccidiosis and drug resistance of field isolates in chickens in China. We examined 545 farms across nine different geographic provinces over a 5-year period. These included Beijing, Sichuan, Zhejiang, Shandong, Guangdong, Fujian, Liaoning Provinces, Inner Mongolia and Xinjiang Uygur Autonomous Regions. The results indicated that oocyst per gram faeces (OPG) and coccidiosis morbidity rate increased when non-prophylactic or low doses of coccidiostats were used. Coccidiosis morbidity rate in Guangdong Province was the highest, leading to greater, more frequent use of diverse types of coccidiostats. Consequently, the Guangdong Province had the most serious drug resistance problem. In contrast, coccidiosis morbidity rates in Inner Mongolia, Fujian and Liaoning were relatively low, leading to a reduced level of coccidiostats use, which resulted in less drug resistance. The threshold of a coccidiosis outbreak was an OPG level of >20000. When the OPG levels were ≥ 50000, chickens were in danger of clinical coccidiosis, and here coccidia generated a certain degree of resistance to the drug when administered. Coccidiostat resistance started to appear when the OPG level reached ca. 20000 using 2 mg kg(-1)/5 mg kg(-1), respectively, of maduramycin, whereas 5 mg kg(-1) of maduramycin developed severe drug resistance. Copyright © 2012 Elsevier B.V. All rights reserved.

  19. Non-steroidal anti-inflammatory drug for pulmonary administration: design and investigation of ketoprofen lysinate fine dry powders.

    Science.gov (United States)

    Stigliani, Mariateresa; Aquino, Rita P; Del Gaudio, Pasquale; Mencherini, Teresa; Sansone, Francesca; Russo, Paola

    2013-05-01

    Pulmonary inflammation is an important therapeutic target in cystic fibrosis (CF) patients, aiming to limit and delay the lung damage. The purpose of the present research was to produce respirable engineered particles of ketoprofen lysinate, a non-steroidal anti-inflammatory drug able to fight lung inflammatory status by direct administration to the site of action. Micronized drug powders containing leucine as dispersibility enhancer were prepared by co-spray drying the active compound and the excipient from water or hydro-alcoholic feeds. Microparticles were fully characterized in terms of process yield, particle size distribution, morphology and drug content. The ability of the drug to reach the deepest airways after aerosolization of spray-dried formulations was evaluated by Andersen cascade impactor, using the monodose DPI as device. In order to investigate the behaviour of the drug once in contact with lung fluid, an artificial CF mucus was prepared. Drug permeation properties were evaluated interposing the mucus layer between the drug and a synthetic membrane mounted in Franz-type diffusion cells. Finally, the effect of the engineered particles on vitality of human airway epithelial cells of patients homozygous for ΔF 508 CF (CuFi1) was studied and compared to that of raw active compound. Results indicated that powders engineering changed the diameter and shape of the particles, making them suitable for inhalation. The mucus layer in the donor compartment of vertical diffusion cells slowed down drug dissolution and permeation, leucine having no influence. Cell proliferation studies evidenced that the spray drying process together with the addition of leucine reduced the cytotoxic effect of ketoprofen lysine salt as raw material, making the ketoprofen lysinate DPI a very promising product for the inflammation control in CF patients.

  20. Experimental investigation on blood magnetic contamination in the presence of drug molecules

    Energy Technology Data Exchange (ETDEWEB)

    Creanga, D E; Nadejde, C [' Al. I. Cuza' University, Faculty of Physics, 11A Blvd. Carol I, RO-700506, Iasi (Romania); Iacob, G H [' Gr. T. Popa' University, Faculty of Biomedical Engineering, Kogalniceanu Street, No. 9-13, RO-700454, Iasi (Romania)], E-mail: nadej_dia@yahoo.com

    2009-05-01

    The purpose of the present project was to study the interference of magnetic nanoparticles with drug molecules - rifampicin, used in lung infectious disease and respectively, sodium diclofenac, an antiinflammatory steroid. The controlled magnetic contamination was accomplished using colloidal nanoparticles supplied from diluted magnetic fluids. Various concentrations of diluted aqueous magnetic fluids, based on magnetite cores coated with citric acid and respectively sodium oleate, were tested. The experiment was focused on the capacity of the magnetic nanoparticles to form reversible complexes with the drug molecules, as well as on the monitoring of the nanoparticle-drug complex dynamics, under the action of external magnetic field. The level of released rifampicin ranged between 4 mg/100 ml and 7 mg/100 ml for the magnetic exposure of 20 mT, while the sodium diclofenac decomplexation level was not higher than 2.5 mg/100 ml under magnetic exposure of 60 mT. The experimental arrangement was proved to be an adequate model for the dynamical study of magnetite reversible complexation with drug molecules, evidencing certain specific values of drug concentration and magnetic field induction that favour such interactions.

  1. Investigating factors leading to fogging of glass vials in lyophilized drug products.

    Science.gov (United States)

    Abdul-Fattah, Ahmad M; Oeschger, Richard; Roehl, Holger; Bauer Dauphin, Isabelle; Worgull, Martin; Kallmeyer, Georg; Mahler, Hanns-Christian

    2013-10-01

    Vial "Fogging" is a phenomenon observed after lyophilization due to drug product creeping upwards along the inner vial surface. After the freeze-drying process, a haze of dried powder is visible inside the drug product vial, making it barely acceptable for commercial distribution from a cosmetic point of view. Development studies were performed to identify the root cause for fogging during manufacturing of a lyophilized monoclonal antibody drug product. The results of the studies indicate that drug product creeping occurs during the filling process, leading to vial fogging after lyophilization. Glass quality/inner surface, glass conversion/vial processing (vial "history") and formulation excipients, e.g., surfactants (three different surfactants were tested), all affect glass fogging to a certain degree. Results showed that the main factor to control fogging is primarily the inner vial surface hydrophilicity/hydrophobicity. While Duran vials were not capable of reliably improving the level of fogging, hydrophobic containers provided reliable means to improve the cosmetic appearance due to reduction in fogging. Varying vial depyrogenation treatment conditions did not lead to satisfying results in removal of the fogging effect. Processing conditions of the vial after filling with drug product had a strong impact on reducing but not eliminating fogging.

  2. Drug ‘‘supersaturation’’ states induced by polymeric micelles and liposomes: A mechanistic investigation into permeability enhancements

    DEFF Research Database (Denmark)

    Di Cagno, Massimiliano; Luppi, Barbara

    2013-01-01

    The objective of this study was to investigate if the increase in apparent solubility induced by liposomalization or micellization of the poorly soluble drug hydrocortisone (HC) would lead to an enhancement of its permeability through biological membranes. For this purpose phosphatidylcholine...... liposome formulations as well as d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) micelle dispersions and polyvinylpyrrolidone (PVP) supersaturated solutions were prepared in order to increase the apparent solubility of HC. Both the apparent solubility of hydrocortisone (i.e. amount of drug...

  3. Investigation on a Potential Targeting Drug Delivery System Consisting of Folate, Mitoxantrone and Human Serum Albumin

    Institute of Scientific and Technical Information of China (English)

    ZHOU Qiu-Jua; BI Ya-Jing; XIANG Jun-Feng; TANG Ya-Lin; YANG Qian-Fan; XU Guang-Zhi

    2008-01-01

    A potential targeting drug delivery system consisting of folate (FA), the targeting molecule, human serum al- bumin (HSA), the carrier, and mitoxantrone (MTO), the medicine, has been designed. Data obtained by UV absorp-tion, fluorescence, and NMR techniques indicated the formation of ternary complexes and possible application to building a targeting drug delivery system by using FA, MTO and HSA. Furthermore, cytotoxicity assay indicated that the toxicity of the FA-HSA-MTO against PC-3 cell line was 79.95%, which was much higher than that of free MTO tested in totally the same conditions. About 30% increase of the toxicity should be owed to the targeting ef-fect of FA. Thus, the feasibility and validity of a novel targeting drug delivery system, FA-HSA-MTO, was con-firmed.

  4. INVESTIGATION OF DRUG RELEASE FROM BIODEGRADABLE PLG MICROSPHERES: EXPERIMENT AND THEORY

    Energy Technology Data Exchange (ETDEWEB)

    ANDREWS, MALCOLM J. [Los Alamos National Laboratory; BERCHANE, NADER S. [Los Alamos National Laboratory; CARSON, KENNETH H. [Los Alamos National Laboratory; RICE-FICHT, ALLISON C. [Los Alamos National Laboratory

    2007-01-30

    Piroxicam containing PLG microspheres having different size distributions were fabricated, and in vitro release kinetics were determined for each preparation. Based on the experimental results, a suitable mathematical theory has been developed that incorporates the effect of microsphere size distribution and polymer degradation on drug release. We show from in vitro release experiments that microsphere size has a significant effect on drug release rate. The initial release rate decreased with an increase in microsphere size. In addition, the release profile changed from first order to concave-upward (sigmoidal) as the system size was increased. The mathematical model gave a good fit to the experimental release data.

  5. Investigation of pharmaceutical drugs and caffeine-containing foods using Fourier and terahertz time-domain spectroscopy

    Science.gov (United States)

    KaraliÅ«nas, Mindaugas; Venckevičius, Rimvydas; Kašalynas, Irmantas; Puc, Uroš; Abina, Andreja; Jeglič, Anton; Zidanšek, Aleksander; Valušis, Gintaras

    2015-08-01

    Several pharmaceutical drugs, such as alprazolam, ibuprofen, acetaminophen, activated carbon and others, and caffeine-containing foods were tested using terahertz (THz) time domain spectroscopy in the range from 0.3 to 2 THz. The dry powder of pharmaceutical drugs was mixed with HDPE and pressed into the pellets using hydraulic press. The coffee grounds were also pressed into the pellets after ball-milling and mixing with HDPE. The caffeine containing liquid foods were dried out on the paper strips of various stacking. Experiments allow one to determine characteristic spectral signatures of the investigated substances within THz range caused by active pharmaceutical ingredients, like in the case of caffeine, as well as supporting pharmaceutical ingredients. Spectroscopic THz imaging approach is considered as a possible option to identify packaged pharmaceutical drugs. The caffeine spectral features in the tested caffeine containing foods are difficult to observed due to the low caffeine concentration and complex caffeine chemical surrounding.

  6. Investigation of different formulations for drug delivery through the nail plate.

    Science.gov (United States)

    Vejnovic, Ivana; Simmler, Linda; Betz, Gabriele

    2010-02-15

    Topical therapies for nail diseases are limited by keratinized cells in the human nail plate. An optimal permeation enhancer would not only improve drug delivery through the nail plate, but would also open new possibilities for treating neighboring target sites if systemic circulation is reached. The aim of the present work was to identify permeation enhancers and to improve the understanding of physicochemical parameters that influence drug permeation. Caffeine served as the model drug, and formulations were prepared in water and 20% (v/v) ethanol/water solutions. Tested enhancers were urea, dimethyl sulfoxide (DMSO), methanol, N-acetyl-L-cysteine (NAC), docusate sodium salt (DSS), boric acid, and fungal proteins, such as hydrophobins. Permeability studies employed cadaver nails in modified Franz-type diffusion cells. The permeability coefficient of caffeine in ethanol/water was determined to be 1.56 E-08 cm/s and was improved to 2.27 E-08 cm/s by the addition of NAC. Formulations containing either methanol or DMSO showed the highest permeability coefficients in the range of 5-7.5 E-08 cm/s. Enhancers could be classified according to their permeation enhancement: methanol>class II hydrophobins>DMSO>followed by class I hydrophobins and urea. Ethanol at a concentration of 20% (v/v) in water did not influence swelling of nail samples. Hydrophobins are suggested to be efficient in drug delivery through the nail plate. Copyright 2009 Elsevier B.V. All rights reserved.

  7. 77 FR 70168 - Guidance for Industry and Food and Drug Administration Staff; The Content of Investigational...

    Science.gov (United States)

    2012-11-23

    ... system that adjusts insulin infusion based upon the continuous glucose monitor via a control algorithm... recommendations for developing premarket submissions for artificial pancreas device systems (APDS) and is the... Pancreas Device Systems; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice....

  8. A spectroscopic investigations of anticancer drugs binding to bovine serum albumin

    Science.gov (United States)

    Bakkialakshmi, S.; Chandrakala, D.

    2012-03-01

    The binding of anticancer drugs (i) Uracil (U), (ii) 5-Fluorouracil (5FU) and (iii) 5-Chlorouracil (5ClU), to bovine serum albumin (BSA) at two levels of temperature was studied by the fluorescence of quenching method. UV/Vis, time-resolved fluorescence, Fourier transform infrared spectroscopy (FTIR), proton nuclear magnetic resonance (1H NMR) and scanning electron microscope (SEM) analyses were also made. Binding constants (Ka) and binding sites (n) at various levels of temperature were calculated. The obtained binding sites were found to be equal to one for all the three quenchers (U, 5FU and 5ClU) at two different temperature levels. Thermodynamic parameters ΔH, ΔG and ΔS have been calculated and were presented in tables. Change in FTIR absorption intensity shows strong binding of anticancer drugs to BSA. Changes in chemical shifts of NMR and fluorescence lifetimes of the drugs indicate the presence of interaction and binding of BSA to anticancer drugs. 1H NMR spectra and SEM photographs also conform this binding.

  9. Perception vs. Reality: An Investigation of the Misperceptions Concerning the Extent of Peer Novel Drug Use

    Science.gov (United States)

    Sanders, Amber; Stogner, John M.; Miller, Bryan Lee

    2013-01-01

    Misperceptions of peer substance use have previously been implicated as significant influences on individual use of both alcohol and illicit drugs. However, research on perceived social norms and related interventions are typically limited to binge drinking and marijuana and no empirical studies have explored misperceptions related to "novel…

  10. Searching for Truth: Internet Search Patterns as a Method of Investigating Online Responses to a Russian Illicit Drug Policy Debate

    Science.gov (United States)

    Gillespie, James A; Quinn, Casey

    2012-01-01

    Background This is a methodological study investigating the online responses to a national debate over an important health and social problem in Russia. Russia is the largest Internet market in Europe, exceeding Germany in the absolute number of users. However, Russia is unusual in that the main search provider is not Google, but Yandex. Objective This study had two main objectives. First, to validate Yandex search patterns against those provided by Google, and second, to test this method's adequacy for investigating online interest in a 2010 national debate over Russian illicit drug policy. We hoped to learn what search patterns and specific search terms could reveal about the relative importance and geographic distribution of interest in this debate. Methods A national drug debate, centering on the anti-drug campaigner Egor Bychkov, was one of the main Russian domestic news events of 2010. Public interest in this episode was accompanied by increased Internet search. First, we measured the search patterns for 13 search terms related to the Bychkov episode and concurrent domestic events by extracting data from Google Insights for Search (GIFS) and Yandex WordStat (YaW). We conducted Spearman Rank Correlation of GIFS and YaW search data series. Second, we coded all 420 primary posts from Bychkov's personal blog between March 2010 and March 2012 to identify the main themes. Third, we compared GIFS and Yandex policies concerning the public release of search volume data. Finally, we established the relationship between salient drug issues and the Bychkov episode. Results We found a consistent pattern of strong to moderate positive correlations between Google and Yandex for the terms "Egor Bychkov" (r s = 0.88, P drug addiction" (r s = .74, P drug addiction" (r s = .68, P problems. The Russian Federation, with its large, geographically dispersed, and politically engaged online population presents unique opportunities for studying the evolving influence of the Internet

  11. FDA’s Proposed Regulations to Expand Access to Investigational Drugs For Treatment Use: The Status Quo in the Guise of Reform

    OpenAIRE

    Rossen, Benjamin

    2008-01-01

    On December 14, 2006, FDA proposed two new regulations in the Federal Register amending current regulations governing expanded access to investigational drugs for treatment use and charging for investigational drugs. The proposal comes at a time when FDA has been under new pressure to provide seriously ill patients with early access to investigational drugs outside the framework of clinical trials. In recent years, patient advocacy groups have filed citizen petitions with FDA asking the agenc...

  12. Drugs-Related Death Soon after Hospital-Discharge among Drug Treatment Clients in Scotland: Record Linkage, Validation, and Investigation of Risk-Factors.

    Directory of Open Access Journals (Sweden)

    Simon R White

    Full Text Available We validate that the 28 days after hospital-discharge are high-risk for drugs-related death (DRD among drug users in Scotland and investigate key risk-factors for DRDs soon after hospital-discharge. Using data from an anonymous linkage of hospitalisation and death records to the Scottish Drugs Misuse Database (SDMD, including over 98,000 individuals registered for drug treatment during 1 April 1996 to 31 March 2010 with 705,538 person-years, 173,107 hospital-stays, and 2,523 DRDs. Time-at-risk of DRD was categorised as: during hospitalization, within 28 days, 29-90 days, 91 days-1 year, >1 year since most recent hospital discharge versus 'never admitted'. Factors of interest were: having ever injected, misuse of alcohol, length of hospital-stay (0-1 versus 2+ days, and main discharge-diagnosis. We confirm SDMD clients' high DRD-rate soon after hospital-discharge in 2006-2010. DRD-rate in the 28 days after hospital-discharge did not vary by length of hospital-stay but was significantly higher for clients who had ever-injected versus otherwise. Three leading discharge-diagnoses accounted for only 150/290 DRDs in the 28 days after hospital-discharge, but ever-injectors for 222/290. Hospital-discharge remains a period of increased DRD-vulnerability in 2006-2010, as in 1996-2006, especially for those with a history of injecting.

  13. Crystallographic investigations of select cathinones: emerging illicit street drugs known as `bath salts'.

    Science.gov (United States)

    Wood, Matthew R; Lalancette, Roger A; Bernal, Ivan

    2015-01-01

    The name `bath salts', for an emerging class of synthetic cathinones, is derived from an attempt to evade prosecution and law enforcement. These are truly illicit drugs that have psychoactive CNS (central nervous system) stimulant effects and they have seen a rise in abuse as recreational drugs in the last few years since first having been seen in Japan in 2006. The ease of synthesis and modification of specific functional groups of the parent cathinone make these drugs particularly difficult to regulate. MDPV (3,4-methylenedioxypyrovalerone) is commonly encountered as its hydrochloride salt (C16H21NO3·HCl), in either the hydrated or the anhydrous forms. This `bath salt' has various names in the US, e.g. `Super Coke', `Cloud Nine', and `Ivory Wave', to name just a few. We report here the structures of two forms of the HCl salt, one as a mixed bromide/chloride salt, C16H22NO3(+)·0.343Br(-)·0.657Cl(-) [systematic name: 1-(benzo[d][1,3]dioxol-5-yl)-2-(pyrrolidin-1-ium-1-yl)pentan-1-one bromide/chloride (0.343/0.657)], and the other with the H7O3(+) cation, as well as the HCl counter-ion [systematic name: hydroxonium 1-(benzo[d][1,3]dioxol-5-yl)-2-(pyrrolidin-1-ium-1-yl)pentan-1-one dichloride, H7O3(+)·C16H22NO3(+)·2Cl(-)]. This is one of a very few structures (11 to be exact) in which we have a new example of a precisely determined hydroxonium cation. During the course of researching the clandestine manufacture of MDPV, we were surprised by the fact that a common precursor of this illicit stimulant is known to be the fragrant species piperonal, which is present in the fragrances of orchids, most particularly in the case of the vanilla orchid. We found that MDPV can be made by a Grignard reaction of this heliotropin. This may also explain the unexpected appearance of the bromide counter-ion in some of the salts we encountered (C16H21NO3·HBr), one of which is presented here [systematic name: 1-(benzo[d][1,3]dioxol-5-yl)-2-(pyrrolidin-1-ium-1-yl)pentan-1-one

  14. [Investigation of fluorescent components of drug "heparin" and its complexing with phenylalanine, tyrosine and tryptophan].

    Science.gov (United States)

    Astakhov, S S; Iunusov, V M; Sultanbaev, M V; Akhmadeeva, G Kh; Iunusov, M S

    2013-01-01

    Using spectral-luminescent and spectrophotometric methods a composition of aminoacidic (AA) and protein components of commercial drug of heparin (Hep) as well as its interaction with Trp, Tyr and Phe was studied. The impurities of aromatic aminoacids Phe, Tyr and elastin protein was revealed in drug of heparin. The quenching of fluorescence (FL) of Trp, Tyr and Phe with heparin was studied and the Stern-Volmer Constants (K) showing the stability of its complexes with aminoacids were determined. The stability of complexes AA...Hep increases in the series K (Trp...Hep) = 19 +/- 2 M(-1) < K (Tyr...Hep) = 39 +/- 3 M(-1) < K (Phe...Hep) = 710 +/- 70 M(-1), that, probably, determines dominating contribution of Phe impurity in heparin and the absence of that of tryptophan. It was assumed, that animal elastin, which is different from human one can provoke allergic reactions up to anaphylactic shock.

  15. Investigation of Microemulsion System for Transdermal Drug Delivery of Amphotericin B

    Institute of Scientific and Technical Information of China (English)

    TIAN Qing-ping; LI Peng; XIE Ke-chang

    2009-01-01

    In order to solve the drawback of poor bioavailability by the oral route and infusion-related side effect for Amphotericin B(AmB), microemulsion vehicles composed of isopropyl myristate(IPM), Tween 80, isopropyl alcohol and water for transdermal delivery of AmB were designed. The pseudo-ternary phase diagrams were constructed by the H2O titration method and the structures of the microemulsion were determined by measuring electrical conducti-vities(σ). The diffusion studies of AmB microemulsion were performed via excised rabbit skin on a drug diffusion apparatus. To obtain a high solubization of AmB, three different methods were tested to incorporate AmB into mi-croemulsion. The result suggests adding AmB in the shape of NaOH solution to the O/W blank microemulsion over the phase inversion temperature(PIT) of the emulsifier obtains the maximum drug content(2.96 mg/mL). The pH value of the system could be adjusted to pH8.5 or pH<5.2, in this range AmB molecules converts from aqueous to the hydrophilic shell of the microemulsion droplets, drug precipitate is no more than 5%, and the formulations were corresponding to the characterizations of microemulsion. At pH 5.14, AmB microemulsion with Km 1:1, O/SC 1:9(mass ratio ofoil phase to surfactant/cosurfactant blend), water content 64.6%, drug content (2.93±0.08) mg/mL,showed the maximum permeation rate(3.255±0.64)μg·cm-2·h-1,which is stable for a long time.

  16. Analysis of Investigational Drugs in Biological Fluids - Method Development and Routine Assay

    Science.gov (United States)

    1994-08-14

    by parasites , including tropical or subtropical zones with drug-resistant forms, the U.S. Army needs to organize programs so that highly active and...has developed resistance towards a number of insecticides widely used for vector control. But, the more alarming reason is that the malarial parasite ...qinghaosu). Planta Med. 1985, 5, 445-6. 47 Brossi A; Venugopalan B; Dominguez Gerpe L; Yeh HIj; Flippen- Anderson JL; Buchs P; Luo XD; Milhous W

  17. Analysis of Investigational Drugs in Biological Fluids. Method Development and Routine Assay. Appendix A.

    Science.gov (United States)

    2007-11-02

    simultaneously on eleven projects (I-WR 238,605, 2-halofantrine (and its metabolite), 3-WR 6026 (and its metabolites), 4- mefloquine (and its metabolite), 5...chloroquine (and its metabolites), and 11-a multiple drug interaction study in dog plasma for WR 238,605, mefloquine , chloroquine, quinine,, doxycycline...245 Study Report 18, WR 6026 in Plasma ................................................................ 259 Study Report 19, Mefloquine (Free Base

  18. Investigating the effect of an arterial hypertension drug on the structural properties of plasma protein.

    Science.gov (United States)

    Hassan, Natalia; Maldonado-Valderrama, Julia; Gunning, A Patrick; Morris, V J; Ruso, Juan M

    2011-10-15

    Propanolol is a betablocker drug used in the treatment of arterial hypertension related diseases. In order to achieve an optimal performance of this drug it is important to consider the possible interactions of propanolol with plasma proteins. In this work, we have used several experimental techniques to characterise the effect of addition of the betablocker propanolol on the properties of bovine plasma fibrinogen (FB). Differential scanning calorimeter (DSC), circular dichroism (CD), dynamic light scattering (DLS), surface tension techniques and atomic force microscopy (AFM) measurements have been combined to carry out a detailed physicochemical and surface characterization of the mixed system. As a result, DSC measurements show that propranolol can play two opposite roles, either acting as a structure stabilizer at low molar concentrations or as a structure destabilizer at higher concentrations, in different domains of fibrinogen. CD measurements have revealed that the effect of propanolol on the secondary structure of fibrinogen depends on the temperature and the drug concentration and the DLS analysis showed evidence for protein aggregation. Interestingly, surface tension measurements provided further evidence of the conformational change induced by propanolol on the secondary structure of FB by importantly increasing the surface tension of the system. Finally, AFM imaging of the fibrinogen system provided direct visualization of the protein structure in the presence of propanolol. Combination of these techniques has produced complementary information on the behavior of the mixed system, providing new insights into the structural properties of proteins with potential medical interest.

  19. Computational and experimental approaches for investigating nanoparticle-based drug delivery systems.

    Science.gov (United States)

    Ramezanpour, M; Leung, S S W; Delgado-Magnero, K H; Bashe, B Y M; Thewalt, J; Tieleman, D P

    2016-07-01

    Most therapeutic agents suffer from poor solubility, rapid clearance from the blood stream, a lack of targeting, and often poor translocation ability across cell membranes. Drug/gene delivery systems (DDSs) are capable of overcoming some of these barriers to enhance delivery of drugs to their right place of action, e.g. inside cancer cells. In this review, we focus on nanoparticles as DDSs. Complementary experimental and computational studies have enhanced our understanding of the mechanism of action of nanocarriers and their underlying interactions with drugs, biomembranes and other biological molecules. We review key biophysical aspects of DDSs and discuss how computer modeling can assist in rational design of DDSs with improved and optimized properties. We summarize commonly used experimental techniques for the study of DDSs. Then we review computational studies for several major categories of nanocarriers, including dendrimers and dendrons, polymer-, peptide-, nucleic acid-, lipid-, and carbon-based DDSs, and gold nanoparticles. This article is part of a Special Issue entitled: Membrane Proteins edited by J.C. Gumbart and Sergei Noskov.

  20. Investigations into the fouling mechanism of parvovirus filters during filtration of freeze-thawed mAb drug substance solutions.

    Science.gov (United States)

    Barnard, James G; Kahn, David; Cetlin, David; Randolph, Theodore W; Carpenter, John F

    2014-03-01

    Filtration to remove viruses is one of the single most expensive steps in the production of mAb drug products. Therefore, virus filtration steps should be fully optimized, and any decline in flow rates warrants investigation into the causes of such membrane fouling. In the current study, it was found that freezing and thawing of a mAb bulk drug solution caused a substantial decrease in viral filter membrane flow rate. Freezing and thawing also caused formation of aggregates and particles across a broad size range, including particles that could be detected by microflow imaging (≥1 μm in size). However, removal of these particles offered little protection against flow rate decline during viral filtration. Further investigation revealed that trace amounts of aggregates (ca. 10⁻⁶ of the total mass of protein in solution) approximately 20-40 nm in size were primarily responsible for the observed membrane fouling.

  1. Investigation and Control of Drug Crime of Logistics%物流毒品犯罪的侦控

    Institute of Scientific and Technical Information of China (English)

    尚德晋; 李波阳

    2012-01-01

    Drug crime of logistics is a newly emerging crime along with the development of China's lo- gistics industry. Owing to the characteristics of low costs, large span,too many channels,hard investiga- tions and being easy to avoid combating,etc. ,drug crime of logistics has gradually developed into a major criminal means by the drug traffickers in the recent years, which has seriously harmed the order of social administration in our nation. Only by deepening the understanding and increasing the awareness of the characteristics of drug crime of logistics as well as by fully utilizing various investigation measures and means,will the investigative organization be able to improve the power and accuracy of cracking down on drug crimes of logistics.%物流毒品犯罪是随着我国物流行业的发展而产生的一种新兴的犯罪,由于物流毒品犯罪具有成本低、跨度大、渠道多、侦破难度大、容易逃避打击等特点,近年逐渐发展成为贩毒分子进行犯罪活动的重要方式,这一犯罪方式严重危害了我国的社会管理秩序。侦查机关只有加深对物流毒品犯罪特点的认识和了解,充分运用各种侦查措施和手段,才能提高对物流毒品犯罪的打击力度和精度。

  2. Investigation of the Relationship of Some Antihypertensive Drugs with Oxidant/Antioxidant Parameters and DNA Damage on Rat Uterus Tissue

    Directory of Open Access Journals (Sweden)

    Mustafa Talip Sener

    2011-01-01

    Full Text Available Background: In this study, we investigated the effects of treatment with chronic antihypertensivedrugs (clonidine, methyldopa, amlodipine, ramipril and rilmenidine on oxidant-antioxidantparameters and toxic effects on DNA in rat uterus tissue. In addition, uterus tissues were examinedhistopathologically.Materials and Methods: A total of 36 albino Wistar rats were divided into the following six groups:0.075 mg/kg clonidine group; 100 mg/kg methyldopa group; 2 mg/kg amlodipine group; 2.5 mg/kgramipril group; 0.5 mg/kg rilmenidine group; and the healthy group. Rats underwent chronic drugadministration for 30 days and at the end, biochemical and histopathological examinations wereperformed. All data were subjected to one-way ANOVA test.Results: We divided these drugs into the following three groups according to their effects on ratuteri: (I mild negative effects (clonidine, (II moderate negative effects (rilmenidine, methyldopaand (III drugs which had severe negative effects (amlodipine, ramipril.Conclusion: These data may help with selection of antihypertensive drugs, in order to determinewhich drugs have the lowest toxicity in pregnant and non-pregnant (pre-pregnancy women.

  3. Comparative phytochemical investigation of the sources of ayurvedic drug Patha: A chromatographic fingerprinting analysis

    Directory of Open Access Journals (Sweden)

    Hullatti K

    2010-01-01

    Full Text Available Standardization of herbal drugs based on their chemical and biological activity profile is an important prerequisite for acquiring the herbal market. The main problem encountered in standardization of Ayurvedic drugs is proper identification of the source plant. The present study was aimed to establish identification characters, quality control parameters, chemical and biological parameters for roots of three plants Cissampelos pareira, Cyclea peltata and Stephania japonica (Fam. Menispermaceae which are being used as source of Patha, in the market. All the three plant were subjected for evaluation of quality control parameters as per WHO guidelines and root extracts and total alkaloidal fractions were subjected for HPTLC and HPLC fingerprinting analysis using a marker compound Bebeerine isolated from roots of Cissampelos pareira. The parameters studied clearly indicated the significant differences among the three plant materials. The roots of Cissampelos pareira can be distinguished from other two plants by presence of high concentration of alkaloids especially the presence of high concentration of pharmacologically active alkaloid bebeerine, which was found to be present in very low concentration in Stephania japonica and absent in roots of Cyclea peltata. The roots of Cyclea peltata were found to contain high concentration of saponins and comparatively in low concentration in Cissampelos pareira where as it was found to be absent in roots of Stephania japonica.

  4. Vibrational and thermal characterisation of a new chiral drug under investigation for the therapy of congestive heart failure

    Science.gov (United States)

    Taddei, Paola; Torreggiani, Armida; Fini, Giancarlo

    2002-12-01

    Racemic (5,6-bis 2-methyl propanoic acid-1,2,3,4-tetrahydro-naphtalen-2-yl)-methylammonium chloride, CHF-1035, under clinical investigation for the treatment of congestive heart failure, was here characterised by Raman and IR spectroscopies coupled with thermal analysis (thermogravimetry and differential scanning calorimetry). These techniques proved suitable for investigating the presence of different polymorphic forms, their relative stability and interconversion tendency in relation to industrial manufacturing processes undergone by the drug (i.e. grinding, compression, heating). Crystallisation experiments were carried out and two different CHF-1035 polymorphic forms were identified. Both grinding and heating revealed to cause a polymorphic transformation of the drug crystal form. It was hypothesised that a change in molecular packing occurs in the drug by effect of both treatments. The possible sources of polymorphism were identified in the -OCOCH(CH 3) groups and in the saturated ring. The non-ground sample showed two endothermic transitions; since they are reversible and not due to desolvation processes the system is probably enantiotropic.

  5. Investigation of Moisture Sorption, Permeability and Drug Release Behavior of Carrageenan/Poly Vinyl Alcohol Films

    Directory of Open Access Journals (Sweden)

    *S. K. Bajpai

    2014-09-01

    Full Text Available This work describes moisture sorption behavior and water vapor permeability of gluteraldehyde –crosslinked Carrageenen/polyvinyl alcohol (Carr/PVA films. The moisture uptake has been studied under various relative humidity (RH and the data obtained has been interpreted in the terms of various isotherm models such as GAB, Oswin and Halsey models. The moisture permeability through the films has been characterized in the terms of various parameters like water vapor transmission rate (WVTR, permeance (P and Water vapor permeability (WVP. It was found that these parameters are greatly affected by the degree of crosslinking of the films. Finally, the model drug Gentamycin Sulphate was loaded in to the films and its release was monitored kinetically in the physiological buffer (PF at 370C. The films exhibited diffusion controlled release mechanism.

  6. NX-1207: a novel investigational drug for the treatment of benign prostatic hyperplasia.

    Science.gov (United States)

    Shore, Neal

    2010-02-01

    Lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) is a common affliction among older men that can have significant impact on health-related quality of life. BPH is a progressive condition that can lead to complications including acute urinary retention (AUR) and to surgical intervention. There is an ongoing need for new, safe and effective treatments for BPH. Currently available therapies have significant safety and efficacy limitations. NX-1207 is a promising first-in-class drug currently in Phase III trials for the treatment of BPH. This review provides an overview of BPH and currently approved medical treatments and drugs as described in the literature and treatment practice guidelines in the past 10 years, an outline of the results of the Phase II trials of NX-1207 and an expert opinion on the role NX-1207 may play in the treatment of men with clinical BPH. This review aims to introduce readers to NX-1207, a new treatment for BPH that is administered in an office-based procedure by transrectal intraprostatic injection under ultrasound guidance. NX-1207 has selective pro-apoptotic properties, which induces focal cell loss in prostate leading to prostate volume reduction with both short- and long-term symptomatic improvement. In four US clinical trials to date, NX-1207 has shown evidence of symptomatic improvement substantially better than currently approved BPH medications with no significant safety issues. Larger Phase III trials are ongoing to further confirm the efficacy, safety and tolerability for this minimally invasive, anesthetic free, clinic-based treatment for BPH.

  7. Investigation of thermo-sensitive amphiphilic micelles as drug carriers for chemotherapy in cholangiocarcinoma in vitro and in vivo.

    Science.gov (United States)

    Wang, Xuefeng; Li, Songgang; Wan, Ziwei; Quan, Zhiwei; Tan, Qinggang

    2014-03-10

    Cholangiocarcinoma is an epithelial cancer of the bile ducts with poor prognosis and, in recent years, a rapidly increasing incidence. In this study, nano-sized thermo-sensitive micelles were investigated as drug carriers to improve chemotherapy in cholangiocarcinoma. Thermo-sensitive amphiphilic block copolymer, P-(N,N-isopropylacrylamide-co-N-hydroxymethylacrylamide)-b-caprolactone [P-(NIPAAm-co-NHMAAm)-b-PCL] with lower critical solution temperature (LCST) at about 38°C was synthesized. Doxorubicin (DOX)-loaded micelles were prepared by dialysis method. The micelles exhibited a sustained and temperature-dependent DOX release. Toxicity of the blank micelles for human cholangiocarcinoma (QBC939) cells was minimal both in vitro and in vivo. In contrast, the DOX-loaded micelles effectively inhibited proliferation and induced apoptosis of QBC939 cells in vitro (pthermo-sensitive amphiphilic micelles are a promising and effective drug carrier, and show potential for improving chemotherapy for cholangiocarcinoma.

  8. 76 FR 70150 - Draft Guidance for Industry and Food and Drug Administration Staff; Investigational Device...

    Science.gov (United States)

    2011-11-10

    ... Staff; Investigational Device Exemptions for Early Feasibility Medical Device Clinical Studies... guidance, FDA intends to facilitate early feasibility studies of medical devices, using appropriate risk mitigation strategies, under the IDE requirements. Early feasibility studies allow for limited early...

  9. 76 FR 80947 - Draft Guidance for Industry and Food and Drug Administration Staff; Investigational Device...

    Science.gov (United States)

    2011-12-27

    ... Staff; Investigational Device Exemptions for Early Feasibility Medical Device Clinical Studies... approaches FDA intends to facilitate early feasibility studies of medical devices, using appropriate risk..., early feasibility studies, as well as outlines the general principles for preparing and reviewing...

  10. Investigational drugs in phase I and phase II clinical trials for thalassemia.

    Science.gov (United States)

    Motta, Irene; Scaramellini, Natalia; Cappellini, Maria Domenica

    2017-07-01

    Regular transfusion and iron chelation are the current treatment of severe forms of thalassemia. As a consequence of this demanding supportive treatment, there are several unmet therapeutic needs. Due to a deeper understanding in the pathophysiology of thalassemia, new therapeutic strategies have been developed that are now in pre-clinical and clinical trials. Areas covered: Activin receptor ligand traps (luspatercept and sotatercept), drugs targeting ineffective erythropoiesis, showed encouraging results in Phase I and II clinical trials. A phase III clinical trial is currently ongoing. Ruxolitinib, a Jak2 inhibitor, has been tested to limit stress erythropoiesis in a phase II clinical trial. In addition, improvement in iron chelation has been developed. Moreover, several trials of gene therapy are currently active in different countries with different lentiviral vectors. Expert opinion: The most promising molecules are the activin receptor ligand traps. Together with gene therapy these could be an alternative to bone marrow transplant, aiming towards a curative strategy. The main limit to gene therapy seems to be the conditioning regimen, thus an in vivo gene therapy would be more suitable. At pre-clinical level gene editing is showing extremely encouraging results.

  11. Investigations into the Antibacterial Activity of the Silver-Based Antibiotic Drug Candidate SBC3

    Directory of Open Access Journals (Sweden)

    Matthias Tacke

    2012-11-01

    Full Text Available The synthesis of N-heterocyclic carbene (NHC silver(I acetate complexes with varying lipophilic benzyl-substituents at the 1 and 3 positions starting from 4,5-diphenylimidazole, opened a new class of antibiotic drug candidates. These NHC-silver(I acetate derivatives exhibit interesting structural motifs in the solid state and proved to be soluble and stable in biological media. The leading candidate, SBC3, which was known to exhibit good antibacterial activity in preliminary Kirby-Bauer tests, was tested quantitatively using minimum inhibitory concentrations. NHC-silver(I acetate complexes were found to have MIC values ranging from 20 to 3.13 μg/mL for a variety of Gram-positive, Gram-negative and mycobacteria tested. These values represent good antibiotic activities against potential pathogens when compared to clinically approved antibiotics. Most striking is the fact that SBC3 is active against methicillin-resistant Staphylococcus aureus with a MIC value of 12.5 μg/mL.

  12. Investigation of polymeric scaffold degradation for drug delivery and neovascularization applications

    Science.gov (United States)

    Bulusu, Kartik V.; Alibouzar, Mitra; Castro, Nathan J.; Zhang, Lijie G.; Sarkar, Kausik; Plesniak, Michael W.

    2016-11-01

    Degradable polymer-based prosthetics for the treatment of osseous tissue defects, maxillo-/cranio-facial trauma and brain injury face two common clinical obstacles impeding efficient tissue engraftment i.e., controlled material release and neovascularization. Ascertaining the time scales of polymer degradation for controlled delivery of drugs and nutrients is critical to treatment efficacy and strategy. We incorporated multiple experimental methodologies to understand the driving forces of transport mechanisms in polyvinyl alcohol-based (PVA) 3D-printed scaffolds of different porosity. Scaffold degradation was monitored various pulsatile flow conditions using MEMS-based pressure catheters and an ultrasonic flow rate sensor. Ultrasonic properties (bulk attenuation and sound velocity) were measured to monitor the degradation process in a static, alkaline medium. Viscosity and the absorption spectra variations with PVA-solute concentrations were measured using a rheometer and a spectrophotometer, respectively. A simple mathematical model based on Fick's law of diffusion provides the fundamental description of solute transport from the scaffold matrices. However, macroscopic material release could become anomalous or non-Fickian in complex polymeric scaffold matrices. Supported by the GW Center for Biomimetics and Bioinspired Engineering and NIH Director's New Innovator Award 1DP2EB020549-01.

  13. Investigation of Fatty Acid Ketohydrazone Modified Liposome’s Properties as a Drug Carrier

    Directory of Open Access Journals (Sweden)

    Keita Hayashi

    2015-01-01

    Full Text Available pH-responsive liposomes were prepared by modifying the liposome with acid-cleaving amphiphiles. Palmitic ketohydrazone (P-KH or stearic ketohydrazone (S-KH, composed of hydrophilic sugar headgroup and hydrophobic acyl chain, was used as a modifier of the DMPC liposome. Because the ketohydrazone group of P-KH or S-KH was cleaved at low pH conditions (drugs from the enzymes in the lysosome. This study shows the novel approach about design of pH-responsive liposomes based on the membrane properties.

  14. SERS investigation of ciprofloxacin drug molecules on TiO2 nanoparticles.

    Science.gov (United States)

    Yang, Libin; Qin, Xiaoyu; Jiang, Xin; Gong, Mengdi; Yin, Di; Zhang, Yingjiu; Zhao, Bing

    2015-07-21

    In this paper, TiO2 nanoparticles (NPs) with different crystallinity served as SERS-active substrates for SERS detection of ciprofloxacin (CIP) drug molecules for the first time. CIP is close to the surface of the TiO2 substrate through the carboxyl group. The mutual SERS enhancement behaviors between CIP molecules and TiO2 NPs were discovered, which are attributed to the contribution of the TiO2-to-molecule charge-transfer mechanism. The crystallinity of TiO2 NPs, the pH value of adsorption solution and the adsorption time have significant influences on the interaction and the SERS behavior between CIP and TiO2. When the calcination temperature of TiO2 NPs is 450 °C, the pH value of adsorption solution is 6 and the adsorption time is 9 h, the CIP molecules on TiO2 NPs exhibit the largest SERS enhancement.

  15. 76 FR 50484 - Draft Guidance for Industry, Clinical Investigators, and Food and Drug Administration Staff...

    Science.gov (United States)

    2011-08-15

    ... Considerations for Pivotal Clinical Investigations for Medical Devices.'' This document is intended to provide... medical devices and for FDA staff who review those submissions. This guidance document describes different study design principles relevant to the development of medical device clinical studies that can be...

  16. Research Costs Investigated: A Study Into the Budgets of Dutch Publicly Funded Drug-Related Research

    NARCIS (Netherlands)

    T. van Asselt (Thea); B.L.T. Ramaekers (Bram); I. Corro Ramos (Isaac); M.A. Joore (Manuela); M.J. Al (Maiwenn); Lesman-Leegte, I. (Ivonne); M.J. Postma (Maarten); P. Vemer (Pepijn); T.L. Feenstra (Talitha)

    2017-01-01

    textabstractBackground: The costs of performing research are an important input in value of information (VOI) analyses but are difficult to assess. Objective: The aim of this study was to investigate the costs of research, serving two purposes: (1) estimating research costs for use in VOI analyses;

  17. A novel QSPR study of normalized migration time for drugs in capillary electrophoresis by new descriptors: quantum chemical investigation.

    Science.gov (United States)

    Riahi, Siavash; Beheshti, Abolghasem; Ganjali, Mohammad Reza; Norouzi, Parviz

    2008-10-01

    Some drugs' migration time (MT) has been studied employing quantitative structure-property relationship using new descriptors that are able to predict MT value with high accuracy. MT property modeling of the drugs was established as a function of the new theoretically derived descriptors applying multiple linear regressions and partial least-squares regression. The genetic algorithm was used to select those variables that resulted in the best-fitted models. To select a set of descriptors that are most relevant to MT, illustrating the affecting degree for the affinity of different descriptors, the linear models with 1-14 variables were constructed and were then investigated based on F-value, squared regression coefficients of cross-validated (Q2), adjusted R2 (R2adj) and standard error of estimate (S) statistical parameters. Finally, the best model with ten variables was selected. Statistical parameters of the test set, such as standard deviation error in test, were 0.559 and 0.616, while relative error of test was equal to 7.648 and 8.497% for multiple linear regressions and partial least-squares models, respectively, confirming the good predictive ability of the model. Since the capillary lengths were not the same for the drugs in the data set, MT values were normalized based on a specific capillary before modeling, which is also one of the advantages of this method, enabling us to use the model for different capillary lengths.

  18. 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.

  19. Investigation on raspberry-like magnetic-hollow silica nanospheres and its preliminary application for drug delivery

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Chunlei; Yan, Juntao, E-mail: yanjuntaonihao@163.com [Wuhan Polytechnic University, College of Chemistry and Environmental Engineering (China); Li, Zhanfeng; Wang, Hongyan; Cui, Xuejun [Jilin University, College of Chemistry (China)

    2013-09-15

    A series of raspberry-like magnetic-hollow silica nanospheres were successfully synthesized via the sol-gel process, which was based on the principle of the electrostatic interaction between negatively charged silica and positively charged polystyrene. The Fe{sub 3}O{sub 4}@SiO{sub 2} particles as the outer shell were compactly assembled on the surface of PS, and then magnetic-hollow nanospheres were obtained by calcination. Different synthesis conditions including the amount of NH{sub 4}OH, TEOS, Fe{sub 3}O{sub 4}, and the adding time of PS were systematically investigated to discuss the influence of these conditions on the morphology and structure. The prepared magnetic-hollow nanospheres were systematically characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), fourier transform infrared spectrometry, energy-dispersive X-ray analysis, thermogravimetric analysis and nitrogen adsorption-desorption measurement. SEM and TEM images exhibited that the obtained samples with the perfect spherical profile and large cavities structure were well monodisperse and uniform under the optimized condition. Zeta-potential analysis was employed to make clear the formation mechanism of raspberry-like PS@Fe{sub 3}O{sub 4}@SiO{sub 2} composite nanosphere. Moreover, the drug release of ibuprofen experiment results demonstrated that the magnetic-hollow nanospheres could be used as a drug carrier to slowly release and deliver drugs.

  20. Study on the Antiradiation role of Melatonin: An investigation on Induced Oxidative Stress Mice by Radiomimetic Drug Cyclophosphamide

    Energy Technology Data Exchange (ETDEWEB)

    Manda, K.; Bhatia, A. L.

    2004-07-01

    Clinical studies have demonstrated an altered pineal function in cancer patients. Owing to the document antineoplastic activity of the pineal gland, these anomalies could have a prognostic significance. This study was carried out to monitor the effect of higher blood levels of melatonin, the most important pineal hormone, which could be applied in relation to the response to chemotherapy in human neoplasms. Cyclophosphamide is a commonly used chemotherapeutic drug and well-known mutagen and clastogen. It is an alkylating agent, producing highly active carbonium ion, which the extremely electron-rich area of the nucleic acids and proteins. The present study aimed to investigate the protective effect of melatonin against cyclophosphamide induced oxidative stress in mice tissues. Lipid perioxidation. Reduced glutathione (GSH), Glutathione disulphide (GSSG), Glutathione peroxidase (GSH-Px) and serum phosphatase level taken as endpoints. Twenty days oral administration with melatonin (0.25 mg/Kg body weight) followed by an acute treatment with cyclophosphamide (75 mg/kg b. w.) inhibited the radiomimetic drug-induced augmented level of lipid peroxidation, Blood GSSG and acid phosphatase. Cyclophosphamide induced depletion in the level of GSH, GSH-Px and alkaline phosphatase is ameliorated significantly by melatonin administration. The findings support the results showing melatonin as a free radical scavenger, and singlet oxygen quencher. Results clearly indicate the antioxidative properties of melatonin against the radiomimetic drug which could be effectively used selectively for the protection of normal tissue during chemotherapy. (Author) 34 refs.

  1. Pharmaceutical systematics: Description and preliminary investigation of an alternative method for structuring drug information

    Directory of Open Access Journals (Sweden)

    Mary E. Kiersma, Pharm.D., M.S.

    2011-01-01

    Full Text Available Objectives: To identify the 30 most common adverse drug events or reactions (ADE/ADRs within the top 200 medications: (1 by raw incidence, (2 weighted by prescription volume, (3 and weighted by retail dollars. Methods: The Pharmacy Times Top 200 Medications (as ranked by prescription volume was utilized to identify the top 200 medications in 2008. The ADE/ADRs for each medication were obtained from Facts and Comparisons, Micromedex, and Lexi-Comp and entered into a database. These ADE/ADRs were compiled and summed, identifying the number of times each appeared. These then were ranked to identify the 30 most common ADE/ADRs. The actual prescription volume and total retail dollars for each medication were obtained and listed next to each medication’s ADE/ADR. The incidence of each ADE/ADR then was weighted by actual prescription volume and retail dollars to determine the top 30 most common ADE/ADRs.Results: Initial evaluation resulted in 9829 individual ADE/ADRs and summed into 1477 distinct ADE/ADRs, after adjusting for interchangeable terminology. Examples of the 30 most common ADE/ADRs (raw incidence included: dizziness/vertigo, headache,nausea, vomiting, and diarrhea/loose stools. The list remained the same after weighting by actual prescription volume. After weighting by retail dollars, the order of ADE/ADRs changed slightly.Conclusion: Knowledge of ADE/ADRs is important for pharmacists in all healthcare settings. Consolidating ADE/ADRs for medications may enable pharmacists to recall the most common side effects and aid in earlier identification of ADE/ADRs, which may positively impact patient safety across practice settings.

  2. Investigation of altered microstructure in patients with drug refractory epilepsy using diffusion tensor imaging

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Yuwei; Yan, Xu; Fan, Mingxia [East China Normal University, Key Laboratory of Magnetic Resonance, Shanghai (China); Mao, Lingyan; Wang, Xin; Ding, Jing [Fudan University, Department of Neurology, Zhongshan Hospital, Shanghai (China); Xu, Dongrong [Columbia University and New York State Psychiatric Institute, MRI Unit/Epidemiology Division, Department of Psychiatry, New York, NY (United States)

    2017-06-15

    The risk of refractory epilepsy can be more dangerous than the adverse effect caused by medical treatment. In this study, we employed voxel-wise analysis (VWA) and tract-based spatial statistics (TBSS) methods to measure microstructural changes using diffusion tensor imaging (DTI) in patients of drug refractory epilepsy (DRE) who had been epileptic for more than 10 years. To examine the specific microstructural abnormalities in DRE patients and its difference from medically controlled epilepsy (MCE), we acquired DTI data of 7 DRE patients, 37 MCE patients, and 31 healthy controls (HCs) using a 3 T MRI scanner. Comparisons between epileptic patients and HCs between MCE and DRE patients were performed based on calculated diffusion anisotropic indices data using VWA and TBSS. Compared to HCs, epileptic patients (including MCE and DRE) showed significant DTI changes in the common affected regions based on VWA, whereas TBSS found that widespread DTI changes in parts of microstructures of bilateral hemispheres were more obvious in the DRE patients than that in the MCE patients when compared with HCs. In contrast, significant reduction of fractional anisotropy values of thalamo-cortical fibers, including left superior temporal gyrus, insular cortex, pre-/post-central gyri, and thalamus, were further found in DRE patients compared with MCE. The results of multiple diffusion anisotropic indices data provide complementary information to understand the dysfunction of thalamo-cortical pathway in DRE patients, which may be contributors to disorder of language and motor functions. Our current study may shed light on the pathophysiology of DRE. (orig.)

  3. Systems Biology-Based Investigation of Cellular Antiviral Drug Targets Identified by Gene-Trap Insertional Mutagenesis.

    Science.gov (United States)

    Cheng, Feixiong; Murray, James L; Zhao, Junfei; Sheng, Jinsong; Zhao, Zhongming; Rubin, Donald H

    2016-09-01

    Viruses require host cellular factors for successful replication. A comprehensive systems-level investigation of the virus-host interactome is critical for understanding the roles of host factors with the end goal of discovering new druggable antiviral targets. Gene-trap insertional mutagenesis is a high-throughput forward genetics approach to randomly disrupt (trap) host genes and discover host genes that are essential for viral replication, but not for host cell survival. In this study, we used libraries of randomly mutagenized cells to discover cellular genes that are essential for the replication of 10 distinct cytotoxic mammalian viruses, 1 gram-negative bacterium, and 5 toxins. We herein reported 712 candidate cellular genes, characterizing distinct topological network and evolutionary signatures, and occupying central hubs in the human interactome. Cell cycle phase-specific network analysis showed that host cell cycle programs played critical roles during viral replication (e.g. MYC and TAF4 regulating G0/1 phase). Moreover, the viral perturbation of host cellular networks reflected disease etiology in that host genes (e.g. CTCF, RHOA, and CDKN1B) identified were frequently essential and significantly associated with Mendelian and orphan diseases, or somatic mutations in cancer. Computational drug repositioning framework via incorporating drug-gene signatures from the Connectivity Map into the virus-host interactome identified 110 putative druggable antiviral targets and prioritized several existing drugs (e.g. ajmaline) that may be potential for antiviral indication (e.g. anti-Ebola). In summary, this work provides a powerful methodology with a tight integration of gene-trap insertional mutagenesis testing and systems biology to identify new antiviral targets and drugs for the development of broadly acting and targeted clinical antiviral therapeutics.

  4. Systems Biology-Based Investigation of Cellular Antiviral Drug Targets Identified by Gene-Trap Insertional Mutagenesis.

    Directory of Open Access Journals (Sweden)

    Feixiong Cheng

    2016-09-01

    Full Text Available Viruses require host cellular factors for successful replication. A comprehensive systems-level investigation of the virus-host interactome is critical for understanding the roles of host factors with the end goal of discovering new druggable antiviral targets. Gene-trap insertional mutagenesis is a high-throughput forward genetics approach to randomly disrupt (trap host genes and discover host genes that are essential for viral replication, but not for host cell survival. In this study, we used libraries of randomly mutagenized cells to discover cellular genes that are essential for the replication of 10 distinct cytotoxic mammalian viruses, 1 gram-negative bacterium, and 5 toxins. We herein reported 712 candidate cellular genes, characterizing distinct topological network and evolutionary signatures, and occupying central hubs in the human interactome. Cell cycle phase-specific network analysis showed that host cell cycle programs played critical roles during viral replication (e.g. MYC and TAF4 regulating G0/1 phase. Moreover, the viral perturbation of host cellular networks reflected disease etiology in that host genes (e.g. CTCF, RHOA, and CDKN1B identified were frequently essential and significantly associated with Mendelian and orphan diseases, or somatic mutations in cancer. Computational drug repositioning framework via incorporating drug-gene signatures from the Connectivity Map into the virus-host interactome identified 110 putative druggable antiviral targets and prioritized several existing drugs (e.g. ajmaline that may be potential for antiviral indication (e.g. anti-Ebola. In summary, this work provides a powerful methodology with a tight integration of gene-trap insertional mutagenesis testing and systems biology to identify new antiviral targets and drugs for the development of broadly acting and targeted clinical antiviral therapeutics.

  5. Systems Biology-Based Investigation of Cellular Antiviral Drug Targets Identified by Gene-Trap Insertional Mutagenesis

    Science.gov (United States)

    Zhao, Junfei; Sheng, Jinsong; Rubin, Donald H.

    2016-01-01

    Viruses require host cellular factors for successful replication. A comprehensive systems-level investigation of the virus-host interactome is critical for understanding the roles of host factors with the end goal of discovering new druggable antiviral targets. Gene-trap insertional mutagenesis is a high-throughput forward genetics approach to randomly disrupt (trap) host genes and discover host genes that are essential for viral replication, but not for host cell survival. In this study, we used libraries of randomly mutagenized cells to discover cellular genes that are essential for the replication of 10 distinct cytotoxic mammalian viruses, 1 gram-negative bacterium, and 5 toxins. We herein reported 712 candidate cellular genes, characterizing distinct topological network and evolutionary signatures, and occupying central hubs in the human interactome. Cell cycle phase-specific network analysis showed that host cell cycle programs played critical roles during viral replication (e.g. MYC and TAF4 regulating G0/1 phase). Moreover, the viral perturbation of host cellular networks reflected disease etiology in that host genes (e.g. CTCF, RHOA, and CDKN1B) identified were frequently essential and significantly associated with Mendelian and orphan diseases, or somatic mutations in cancer. Computational drug repositioning framework via incorporating drug-gene signatures from the Connectivity Map into the virus-host interactome identified 110 putative druggable antiviral targets and prioritized several existing drugs (e.g. ajmaline) that may be potential for antiviral indication (e.g. anti-Ebola). In summary, this work provides a powerful methodology with a tight integration of gene-trap insertional mutagenesis testing and systems biology to identify new antiviral targets and drugs for the development of broadly acting and targeted clinical antiviral therapeutics. PMID:27632082

  6. Exploratory safety pharmacology: a new safety paradigm to de-risk drug candidates prior to selection for regulatory science investigations.

    Science.gov (United States)

    Cavero, Icilio

    2009-11-01

    The primary objective of Safety Pharmacology is to ensure the safety of medicines on physiological functions in order to protect humans against adverse drug reactions. Safety Pharmacology became a major non-clinical discipline in 2000 when the International Conference on Harmonization approved the S7A guideline. This regulatory document requires pharmaceutical companies to undertake Safety Pharmacology assessment under Good Laboratory Practice (GLP) in order to guarantee the absence of unmanageable risks on vital organ function for compounds to be tested on humans. These regulatory studies often reveal liabilities impacting on the smooth transition of drug candidates from the discovery phase into the clinical arena. However, if these safety issues were uncovered prior to regulatory science assessment, the chemistry of poorly safe molecules could be modified during the lead optimisation phase for preventing later occurring attrition accidents. This article proposes the establishment of a spin-off specialty of Regulatory Safety Pharmacology, for which the name 'Exploratory Safety Pharmacology' is proposed. The objective of this discipline would be to conduct early safety investigations on potential drug candidates by applying, outside the constraints of GLP, in silico, in vitro, ex vivo and in vivo platforms translating clinical liabilities into simple, fast and cost-effective screening assays. This approach should result in early hazard detection with rapid turnaround of the data, enabling medicinal chemists to mitigate the safety liabilities of new compounds in an iterative manner. Hence, the ultimate aim of Exploratory Safety Pharmacology activities is to transform Regulatory Safety Pharmacology investigations into risk-known exercises.

  7. Effect of drug precursors and chemicals relevant to clandestine laboratory investigation on plastic bags used for collection and storage.

    Science.gov (United States)

    Michelot, Harmonie; Fu, Shanlin; Stuart, Barbara; Shimmon, Ronald; Raymond, Tony; Crandell, Tony; Roux, Claude

    2017-04-01

    In the area of clandestine laboratory investigations, plastic bags are used to collect and store evidence, such as solvents, precursors, and other compounds usually employed for the manufacturing of drugs (although liquids may be stored in glass containers within the bags first). In this study, three different types of plastic bags were provided by the NSW Police Force and investigated for their suitability for evidence collection: two different types of low-density polyethylene (LDPE) bags and one type of polyvinyl chloride (PVC) bag. Three different experiments were carried out: (1) storing relevant chemicals in the bags for up to three months; (2) exposing the bags including their content to accelerated conditions using a weatherometer, and (3) simulating an expected real case scenario. This study indicates that drugs and related chemicals stored in plastic bags may lead to a change in the composition of the chemical and an alteration or degradation of the plastic bag. All experiments led to the same conclusion: the polyvinyl chloride bags appeared to be the most affected. LDPE bags seem to be more appropriate for routine use, although it has been established they are not suitable for the collection of liquids (unless pre-packaged in, for instance, a glass container).

  8. Investigation and correlation of drug polymer miscibility and molecular interactions by various approaches for the preparation of amorphous solid dispersions.

    Science.gov (United States)

    Meng, Fan; Trivino, Anne; Prasad, Dev; Chauhan, Harsh

    2015-04-25

    Curcumin (CUR) was used as a poorly soluble drug whereas polyvinyl pyrrolidone K90 (PVP), Eudragit EPO (EPO), hydroxypropyl methylcellulose E5 (HPMC) and polyethylene glycol 8000 (PEG) were used as hydrophilic polymers. CUR polymer miscibility was evaluated by solubility parameter, melting point depression and glass transition temperature (Tg) measurements. Molecular interactions between CUR and polymers were determined by Fourier-transform infrared spectroscopy (FTIR) and Raman. Amorphous solid dispersions were prepared with CUR-polymer ratio of 70:30 (w/w) by solvent evaporation technique and were evaluated for dissolution enhancement using USP II method. Physical states of solid dispersions were characterized by X-ray diffraction (XRD) whereas thermal behaviors were investigated using modulated differential scanning calorimetry (MDSC). CUR-EPO system showed good miscibility through all the approaches, whereas immiscibility was found in other CUR-polymer systems. CUR-EPO and CUR-HPMC systems showed significant molecular interactions whereas CUR-PVP and CUR-PEG showed no molecular interactions. All solid dispersions showed significant dissolution enhancement with CUR-EPO showing highest dissolution rate during first 1h whereas CUR-HPMC was effective in maintaining high CUR concentrations for 6h. The study highlights the importance of investigating and correlating drug polymer miscibility and molecular interactions by various approaches for successful formulation of amorphous solid dispersions.

  9. Effect of red clover on cyp expression: An investigation of herb-drug interaction at molecular level

    Directory of Open Access Journals (Sweden)

    Anubhuti Tripathi

    2014-01-01

    Full Text Available Hormone replacement therapy and selective estrogen receptor modulator are the most common therapy for women going through menopause. These therapies though popular fail to relieve withdrawal symptoms such as hot flashes, fatigue, leg cramps and nausea. This scenario necessitates to herbal preparations as alternative which may lead to simultaneous intake of herbal preparations, containing flavonoids, as well as Selective estrogen receptor modulator hence creating a phenomenon of herb drug interaction. Here we investigate the effect of red clover on steady state mRNA levels of rat cytochrome P 450 enzymes. Further, red clover′s effect on cytochrome P 450′s expression has been investigated when co-administered with tamoxifen and raloxifene. Exposure to red clover resulted in significant down regulation of all the cytochrome P 450 isoform mRNA except cytochrome P 450 2C13 and cytochrome P 450 3A2. When red clover is given in combination with tamoxifen or raloxifene altered level of cytochrome P 450 enzyme mRNA is observed. Present results suggest that herbal medical preparations such red clover has potential for herb drug interaction.

  10. Effect of Red Clover on CYP Expression: An Investigation of Herb-Drug Interaction at Molecular Level

    Science.gov (United States)

    Tripathi, Anubhuti; Singh, S. P.; Raju, K. S. R.; Wahajuddin; Gayen, J. R

    2014-01-01

    Hormone replacement therapy and selective estrogen receptor modulator are the most common therapy for women going through menopause. These therapies though popular fail to relieve withdrawal symptoms such as hot flashes, fatigue, leg cramps and nausea. This scenario necessitates to herbal preparations as alternative which may lead to simultaneous intake of herbal preparations, containing flavonoids, as well as Selective estrogen receptor modulator hence creating a phenomenon of herb drug interaction. Here we investigate the effect of red clover on steady state mRNA levels of rat cytochrome P 450 enzymes. Further, red clover's effect on cytochrome P 450's expression has been investigated when co-administered with tamoxifen and raloxifene. Exposure to red clover resulted in significant down regulation of all the cytochrome P 450 isoform mRNA except cytochrome P 450 2C13 and cytochrome P 450 3A2. When red clover is given in combination with tamoxifen or raloxifene altered level of cytochrome P 450 enzyme mRNA is observed. Present results suggest that herbal medical preparations such red clover has potential for herb drug interaction. PMID:25035541

  11. Structure investigation of sertraline drug and its iodine product using mass spectrometry, thermal analyses and MO-calculations

    Science.gov (United States)

    Zayed, M. A.; Hawash, M. F.; Fahmey, M. A.; El-Habeeb, Abeer A.

    2007-11-01

    Sertraline (C 17H 17Cl 2N) as an antidepressant drug was investigated using thermal analysis (TA) measurements (TG/DTG and DTA) in comparison with electron impact (EI) mass spectral (MS) fragmentation at 70 eV. Semi-empirical MO-calculations, using PM3 procedure, has been carried out on neutral molecule and positively charged species. These calculations included bond length, bond order, bond strain, partial charge distribution and heats of formation (Δ Hf). Also, in the present work sertraline-iodine product was prepared and its structure was investigated using elemental analyses, IR, 1H NMR, 13C NMR, MS and TA. It was also subjected to molecular orbital calculations (MOC) in order to confirm its fragmentation behavior by both MS and TA in comparison with the sertraline parent drug. In MS of sertraline the initial rupture occurred was CH 3NH 2+ fragment ion via H-rearrangement while in sertraline-iodine product the initial rupture was due to the loss of I + and/or HI + fragment ions followed by CH 2dbnd NH + fragment ion loss. In thermal analyses (TA) the initial rupture in sertraline is due to the loss of C 6H 3Cl 2 followed by the loss of CH 3-NH forming tetraline molecule which thermally decomposed to give C 4H 8, C 6H 6 or the loss of H 2 forming naphthalene molecule which thermally sublimated. In sertraline-iodine product as a daughter the initial thermal rupture is due to successive loss of HI and CH 3NH followed by the loss of C 6H 5HI and HCl. Sertraline biological activity increases with the introduction of iodine into its skeleton. The activities of the drug and its daughter are mainly depend upon their fragmentation to give their metabolites in vivo systems, which are very similar to the identified fragments in both MS and TA. The importance of the present work is also due to the decision of the possible mechanism of fragmentation of the drug and its daughter and its confirmation by MOC.

  12. Illicit drug detection with laser 1: investigation of optimal parameters in stomach tissue

    Science.gov (United States)

    Özer, Ayşen Gürkan; Tabakoğlu, Haşim Özgür; Cengiz, Salih

    2014-05-01

    The main purpose of this study is to establish radiation-safe scanning of passersby at high security areas, such as airports and customs. The stomach was selected as the organ to be analyzed. In order to determine whether a substance found inside a human body as wrapped in a plastic bag is filled narcotics or not, many substances in white powder form including morphine-HCL were inspected. Inspection was carried out with on-ionizing radiation by irradiating stomach tissue with laser light. Optical transmittance of lamb stomach tissue was analyzed at different wavelengths. We showed that detection by 650-nm diode laser irradiation would be suitable for such a radiation-safe scan. Different materials were also investigated for absorptive properties, and closed system Raman studies were performed. The spectrum of a molecule found inside white powder placed behind the lamb stomach tissue was detected as a fingerprint. This allowed the detection of target substances without any physical contact or damage to the biological tissue.

  13. In vitro model systems to investigate bile salt export pump (BSEP) activity and drug interactions: A review.

    Science.gov (United States)

    Cheng, Yaofeng; Woolf, Thomas F; Gan, Jinping; He, Kan

    2016-08-05

    The bile salt export pump protein (BSEP), expressed on the canalicular membranes of hepatocytes, is primarily responsible for the biliary excretion of bile salts. The inhibition of BSEP transport activity can lead to an increase in intracellular bile salt levels and liver injury. This review discusses the various in vitro assays currently available for assessing the effect of drugs or other chemical entities to modulate BSEP transport activity. BSEP transporter assays use one of the following platforms: Xenopus laevis oocytes; canalicular membrane vesicles (CMV); BSEP-expressed membrane vesicles; cell lines expressing BSEP; sandwich cultured hepatocytes (SCH); and hepatocytes in suspension. Two of these, BSEP-expressed insect membrane vesicles and sandwich cultured hepatocytes, are the most commonly used assays. BSEP membrane vesicles prepared from transfected insect cells are useful for assessing BSEP inhibition or substrate specificity and exploring mechanisms of BSEP-associated genetic diseases. This model can be applied in a high-throughput format for discovery-drug screening. However, experimental results from use of membrane vesicles may lack physiological relevance and the model does not allow for investigation of in situ metabolism in modulation of BSEP activity. Hepatocyte-based assays that use the SCH format provide results that are generally more physiologically relevant than membrane assays. The SCH model is useful in detailed studies of the biliary excretion of drugs and BSEP inhibition, but due to the complexity of SCH preparation, this model is used primarily for determining biliary clearance and BSEP inhibition in a limited number of compounds. The newly developed hepatocyte in suspension assay avoids many of the complexities of the SCH method. The use of pooled cryopreserved hepatocytes in suspension minimizes genetic variance and individual differences in BSEP activity and also provides the opportunity for higher throughput screening and cross

  14. Hot melt extruded amorphous solid dispersion of posaconazole with improved bioavailability: investigating drug-polymer miscibility with advanced characterisation.

    Science.gov (United States)

    Fule, Ritesh; Amin, Purnima

    2014-01-01

    Invasive antifungal infections are reasons for morbidity and mortality in immunogenic patients worldwide. Posaconazole is a most promising antifungal agent against all types of invasive infections with high % of cure rate. The marketed suspension formulation has low bioavailability and is needed to be taken with food. In this paper, PCZ hot melt extruded amorphous solid dispersion (SD) with immediate release and improved bioavailability was prepared using Soluplus (Sol) as primary carrier for solubilization. Surfactants such as PEG 400, Lutrol F27, Lutrol F68, and TPGS are also used in combination with Soluplus to improve the physicochemical performance of the formulation when it comes in contact with GI (gastrointestinal) fluid. Drug-polymer miscibility of SD was investigated using advanced techniques. In the in vivo study, the AUC(0-72) and C(max) of PCZ/Soluplus were 11.5 and 11.74 time higher than those of pure PCZ. The formulation of the extrudate SD had an AUC(0-72) and C(max) higher than those with the commercial capsule (Noxafil). Molecular dynamic (MD) simulation studies were carried out using in silico molecular modelling to understand the drug-polymer intermolecular behaviour. The results of this research ensure enhanced dissolution and bioavailability of the solid dispersion of PCZ prepared by HME compared with the PCZ suspension.

  15. Development and evaluation of lafutidine solid dispersion via hot melt extrusion: Investigating drug-polymer miscibility with advanced characterisation

    Directory of Open Access Journals (Sweden)

    Ritesh Fule

    2014-04-01

    Full Text Available In current study, immediate release solid dispersion (SD formulation of antiulcer drug lafutidine (LAFT was developed using hot melt extrusion (HME technique. Amphiphilic Soluplus® used as a primary solubilizing agent, with different concentrations of selected surfactants like PEG 400, Lutrol F127 (LF127, Lutrol F68 (LF68 were used to investigate their influence on formulations processing via HME. Prepared amorphous glassy solid dispersion was found to be thermodynamically and physicochemically stable. On the contrary, traces of crystalline LAFT not observed in the extrudates according to differential scanning calorimetry (DSC, X-ray diffraction (XRD, scanning electron microscopy (SEM and Raman spectroscopy. Raman micro spectrometry had the lowest detection limit of LAFT crystals compared with XRD and DSC. Atomic Force microscopy (AFM studies revealed drug- polymer molecular miscibility and surface interaction at micro level. 1H–COSY NMR spectroscopy confirmed miscibility and interaction between LAFT and Soluplus®, with chemical shift drifting and line broadening. MD simulation studies using computational modelling showed intermolecular interaction between molecules. Dissolution rate and solubility of LAFT was enhanced remarkably in developed SD systems. Optimized ratio of polymer and surfactants played crucial role in dissolution rate enhancement of LAFT SD. The obtained results suggested that developed LAFT has promising potential for oral delivery and might be an efficacious approach for enhancing the therapeutic potential of LAFT.

  16. Hot Melt Extruded Amorphous Solid Dispersion of Posaconazole with Improved Bioavailability: Investigating Drug-Polymer Miscibility with Advanced Characterisation

    Directory of Open Access Journals (Sweden)

    Ritesh Fule

    2014-01-01

    Full Text Available Invasive antifungal infections are reasons for morbidity and mortality in immunogenic patients worldwide. Posaconazole is a most promising antifungal agent against all types of invasive infections with high % of cure rate. The marketed suspension formulation has low bioavailability and is needed to be taken with food. In this paper, PCZ hot melt extruded amorphous solid dispersion (SD with immediate release and improved bioavailability was prepared using Soluplus (Sol as primary carrier for solubilization. Surfactants such as PEG 400, Lutrol F27, Lutrol F68, and TPGS are also used in combination with Soluplus to improve the physicochemical performance of the formulation when it comes in contact with GI (gastrointestinal fluid. Drug-polymer miscibility of SD was investigated using advanced techniques. In the in vivo study, the AUC(0–72 and Cmax of PCZ/Soluplus were 11.5 and 11.74 time higher than those of pure PCZ. The formulation of the extrudate SD had an AUC(0–72 and Cmax higher than those with the commercial capsule (Noxafil. Molecular dynamic (MD simulation studies were carried out using in silico molecular modelling to understand the drug-polymer intermolecular behaviour. The results of this research ensure enhanced dissolution and bioavailability of the solid dispersion of PCZ prepared by HME compared with the PCZ suspension.

  17. Investigation of drug-excipient interactions in lapatinib amorphous solid dispersions using solid-state NMR spectroscopy.

    Science.gov (United States)

    Song, Yang; Yang, Xinghao; Chen, Xin; Nie, Haichen; Byrn, Stephen; Lubach, Joseph W

    2015-03-02

    This study investigated the presence of specific drug-excipient interactions in amorphous solid dispersions of lapatinib (LB) and four commonly used pharmaceutical polymers, including Soluplus, polyvinylpyrrolidone vinyl acetate (PVPVA), hydroxypropylmethylcellulose acetate succinate (HPMCAS), and hydroxypropylmethylcellulose phthalate (HPMCP). Based on predicted pKa differences, LB was hypothesized to exhibit a specific ionic interaction with HPMCP, and possibly with HPMCAS, while Soluplus and PVPVA were studied as controls without ionizable functionality. Thermal studies showed a single glass transition (Tg) for each dispersion, in close agreement with predicted values for Soluplus, PVPVA, and HPMCAS systems. However, the Tg values of LB-HPMCP solid dispersions were markedly higher than predicted values, indicating a strong intermolecular interaction between LB and HPMCP. (15)N solid-state NMR provided direct spectroscopic evidence for protonation of LB (i.e., salt formation) within the HPMCP solid dispersions. (1)H T1 and (1)H T1ρ relaxation studies of the dispersions supported the ionic interaction hypothesis, and indicated multiple phases in the cases of excess drug or polymer. In addition, the dissolution and stability behavior of each system was examined. Both acidic polymers, HPMCAS and HPMCP, effectively inhibited the crystallization of LB on accelerated stability, likely owing to beneficial strong intermolecular hydrogen and/or specific ionic bonds with the acidic polymers. Soluplus and PVPVA showed poor physical properties on stability and subsequently poor crystallization inhibition.

  18. Investigation of herb-drug interactions with ginkgo biloba in women receiving hormonal treatment for early breast cancer.

    Science.gov (United States)

    Vardy, Janette; Dhillon, Haryana M; Clarke, Stephen J; Olesen, Inger; Leslie, Felicity; Warby, Anne; Beith, Jane; Sullivan, Anne; Hamilton, Anne; Beale, Philip; Rittau, Anneliese; McLachlan, Andrew J

    2013-12-01

    Women receiving treatment for breast cancer commonly ingest herbal medicines. Little is known about the potential for herb-drug interactions in this population. The aim of this study is to investigate the effect of ginkgo biloba co-administration on the pharmacokinetics of tamoxifen, anastrozole and letrozole. This was a prospective open-label cross-over study in 60 women with early stage breast cancer taking either tamoxifen, anastrozole or letrozole (n=20/group). Participants received ginkgo biloba (EGb 761) for 3 weeks (120 mg twice daily). Trough concentrations of drugs were measured before and after ginkgo biloba treatment using LC-MS/MS. Toxicities were graded according to National Cancer Institute Common Terminology Criteria for Adverse Events. Trough concentrations before and after treatment with ginkgo biloba were not significantly different for tamoxifen (93.5 ± 29.0, 86.5 ± 25.3 ng/mL; p=0.16), letrozole (91.1 ± 50.4, 89.6 ± 52.14 ng/mL; p=0.60) or anastrozole (29.1 ± 8.6, 29.1 ± 7.6 ng/mL; p=0.97). Ginkgo biloba was well tolerated, with no difference in toxicity during ginkgo biloba. Co-administration of ginkgo biloba does not significantly affect the pharmacokinetics of tamoxifen, anastrozole or letrozole. There was no difference in the toxicity profile of hormone therapy with ginkgo biloba use in women with early stage breast cancer.

  19. The Investigators' Brochure: a comparison of the draft international conference on harmonisation guideline with current Food and Drug Administration requirements.

    Science.gov (United States)

    Cocchetto, D M

    1995-12-01

    For several years, the United States Food and Drug Administration (FDA) has participated in a collaborative effort to harmonize the technical procedures for development and regulatory approval of human pharmaceuticals in multiple countries. This harmonization effort is the work of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). At this point, ICH focuses on achieving harmonization of technical requirements in three major regions of the world, i.e., the United States, European Union, and Japan. One area for which harmonization is being sought is the format and content of the Investigators' Brochure. On October 27, 1993, the ICH Steering Committee agreed that the ICH draft guideline on the Investigators' Brochure should be made available for public comment. On August 9, 1994, the FDA published the draft guideline for the format and content of the Investigators' Brochure. This draft guideline was prepared by the Efficacy Expert Working Group of the ICH. FDA solicited written comments on this draft guideline until October 11, 1994. Ultimately, FDA intends to adopt the ICH Steering Committee's final guidelines on Investigators' Brochures as part of a larger document on good clinical practices. Therefore, the content of this draft guideline warrants careful attention. In this paper, ICH's proposed information for inclusion in the Investigators' Brochure is reviewed and compared with current regulatory requirements of FDA. The expanded contents of the Investigators' Brochure proposed by ICH, which represent potential new requirements beyond current FDA regulations, are highlighted. The major controversial elements of this draft guideline are summarized.

  20. Investigating the Impact of Herbal Medicines Marketing Mix and Physicians' Product Involvement on Prescription of these Drugs

    Directory of Open Access Journals (Sweden)

    Bahram Ranjbarian

    2013-11-01

    Full Text Available Although the main side effects of chemical medicines have been discovered, the level of using herbal medicines is still low in Iran. Today prescribing herbal medicines along with chemical ones have different kinds of advantages including: increased health rate in society and developed job opportunities in the fields of agriculture, medicine industry and all of related processes. In our country there are few researches in which the important factors influencing the prescription of herbal medicines have been investigated. Thus to fill this gap the main purpose of this paper is to study the impact of marketing mix of herbal medicines and physicians’ involvement about these drugs on prescribing them. Thus to develop this research 253 doctors in Isfahan were evaluated. In order to examine the main hypotheses Spss19, Structural Equation Modeling (SEM and Amos graphic have been used. Results showed that marketing mix and all of its components and also physicians' product Involvement affect prescribing of herbal medicines.

  1. Investigations of the effects of the antimalarial drug dihydroartemisinin (DHA) using the Frog Embryo Teratogenesis Assay-Xenopus (FETAX).

    Science.gov (United States)

    Longo, Monica; Zanoncelli, Sara; Della Torre, Paola; Rosa, Francesco; Giusti, AnnaMaria; Colombo, Paolo; Brughera, Marco; Mazué, Guy; Olliaro, Piero

    2008-08-01

    Artemisinin derivatives are effective and safe drugs for treating malaria, but they are not recommended during the first trimester of pregnancy because of resorptions and abnormalities observed in animal reproduction studies. Previous studies in rats showed that artemisinin embryotoxicity derives from the depletion of primitive red blood cells (RBCs) over a narrow critical time window (gestation Days 9-14). In order to further investigate the susceptibility of primitive RBCs to artemisinins and to establish whether this susceptibility is species-specific or inherent to the compound, we studied dihydroartemisinin (DHA), both a drug in its own right and the main metabolite of current artemisinin derivatives in use, in the Frog Embryo Teratogenesis Assay-Xenopus (FETAX). This model readily allows investigation and monitoring of primitive and definitive RBCs. Effects on frog larvae exposed to DHA for 48 h during early embryonic development, starting from 24 h post fertilization, were similar to those on rat embryos in terms of reduction in the number of primitive RBCs (clonally produced within the ventral blood island). In contrast, RBCs of older larvae (stage 47, produced at the definitive sites of hematopoiesis) were affected minimally and subsequently recovered. Compared to rat embryos, the frog larvae had no areas of necrosis but they shared similar heart defects. The mitochondrion appeared to be the main subcellular target, similar to observations in Plasmodium. These results implicate artemisinin-induced embryotoxicity through perturbation of metabolically active RBCs; whereas this mode of action does not appear to be species-specific, the stages of susceptibility varied between different species. The window of susceptibility and duration of exposure must be considered to evaluate the clinical relevance of these findings.

  2. The United States Army Criminal Investigation Command and Its Role in the Army’s War on Drugs

    Science.gov (United States)

    1993-04-15

    of cases involving marihuana , narcotics, dangerous drugs, or other controlled substances. Drug suppression, as conducted by USACIDC, refers to law...of particular -- 40 percent of soiders In theyounger ago groups have used legal drugs, principally marthuana, at some concern to the Army’s leadership...younger age groups have used illegal drugs, orincipally marihuana , at sometime during their lives -- not necessarl-y since entering the Army. In

  3. Access to Investigational Drugs

    Science.gov (United States)

    ... by searching NCI’s clinical trials database or by calling NCI’s Cancer Information Service (CIS) at 1–800– ... that are written by individuals from outside the government may be owned by the writer, and graphics ...

  4. Electrospun DOXY-h loaded-poly(acrylic acid) nanofiber mats: in vitro drug release and antibacterial properties investigation.

    Science.gov (United States)

    Khampieng, Thitikan; Wnek, Gary E; Supaphol, Pitt

    2014-01-01

    Electrospun DOXY-h loaded-poly(acrylic acid) (PAA) nanofiber mats (PAA/DOXY-h nanofiber mats) were prepared by the electrospinning technique and post-spinning sorption method at various doses: PAA/DOXY-h125, PAA/DOXY-h250, PAA/DOXY-h500, and PAA/DOXY-h1000. The morphology, drug content, release characteristics, and antibacterial activities of the PAA/DOXY-h nanofiber mats were investigated with scanning electron microscopy, UV-vis spectrophotometry, and disc diffusion methodology. The PAA/DOXY-h nanofiber mats had a diameter range of 285-340 nm, and a smooth surface without beads. Adsorption isotherms of DOXY-h could be described well with the Freundlich model. The amounts of DOXY-h, after the post-spinning sorption process, in the PAA/DOXY-h nanofiber mats ranged between 27.57 and 101.71 mg/g. All of the PAA/DOXY-h nanofiber mats exhibited an initial burst release characteristic with cumulative releasing percentages between 37.14 and 45.97%, which followed the Fickian diffusion mechanism. Based on the antibacterial investigation, the tested gram-positive bacteria, Staphylococcus aureus and Streptococcus agalactiae, seemed to be more sensitive to PAA/DOXY-h nanofiber mats than the tested gram-negative bacteria, Pseudomonas aeruginosa. These PAA/DOXY-h nanofiber mats could be used as an antibacterial wound dressing.

  5. Influence of Physiological Gastrointestinal Surfactant Ratio on the Equilibrium Solubility of BCS Class II Drugs Investigated Using a Four Component Mixture Design.

    Science.gov (United States)

    Zhou, Zhou; Dunn, Claire; Khadra, Ibrahim; Wilson, Clive G; Halbert, Gavin W

    2017-08-22

    The absorption of poorly water-soluble drugs is influenced by the luminal gastrointestinal fluid content and composition, which control solubility. Simulated intestinal fluids have been introduced into dissolution testing including endogenous amphiphiles and digested lipids at physiological levels; however, in vivo individual variation exists in the concentrations of these components, which will alter drug absorption through an effect on solubility. The use of a factorial design of experiment and varying media by introducing different levels of bile, lecithin, and digested lipids has been previously reported, but here we investigate the solubility variation of poorly soluble drugs through more complex biorelevant amphiphile interactions. A four-component mixture design was conducted to understand the solubilization capacity and interactions of bile salt, lecithin, oleate, and monoglyceride with a constant total concentration (11.7 mM) but varying molar ratios. The equilibrium solubility of seven low solubility acidic (zafirlukast), basic (aprepitant, carvedilol), and neutral (fenofibrate, felodipine, griseofulvin, and spironolactone) drugs was investigated. Solubility results are comparable with literature values and also our own previously published design of experiment studies. Results indicate that solubilization is not a sum accumulation of individual amphiphile concentrations, but a drug specific effect through interactions of mixed amphiphile compositions with the drug. This is probably due to a combined interaction of drug characteristics; for example, lipophilicity, molecular shape, and ionization with amphiphile components, which can generate specific drug-micelle affinities. The proportion of each component can have a remarkable influence on solubility with, in some cases, the highest and lowest points close to each other. A single-point solubility measurement in a fixed composition simulated media or human intestinal fluid sample will therefore provide a

  6. Investigation of the in vitro performance difference of drug-Soluplus® and drug-PEG 6000 dispersions when prepared using spray drying or lyophilization

    Directory of Open Access Journals (Sweden)

    Mohammad A. Altamimi

    2017-03-01

    Full Text Available Purpose: To evaluate the physicochemical and in vitro characteristics of solid dispersions using BCS II model drugs with Soluplus® and one of its component homopolymers, PEG 6000. Methods: Nifedipine (NIF and sulfamethoxazole (SMX of 99.3% and 99.5% purity, respectively, were selected as BCS II model drugs, such that an improved dissolution rate and concentration in the gastrointestinal tract should increase oral bioavailability. Soluplus® is an amorphous, tri-block, graft co-polymer with polyvinyl caprolactam, polyvinyl acetate, and polyethylene glycol (PCL:PVAc:PEG6000 in the ratio 57:30:13. PEG 6000 (BASF is a waxy material with melting point of about 60 °C. Solid dispersions were prepared using lyophilization or spray drying techniques. Dissolution study, crystallinity content, and analysis for new chemical bond formation have been used to evaluate the dispersed materials. Results: Although each polymer improved the drug dissolution rate, dissolution from Soluplus® was slower. Enhanced dissolution rates were observed with NIF solid dispersions, but the dissolution profiles were quite different due to the selected technique, polymer, and dissolution medium. For SMX, there was similarity across the dissolution profiles despite the medium, polymer, or applied technique. Each polymer was able to maintain an elevated drug concentration over the three hour duration of the dissolution profile, i.e., supersaturation was supported by the polymer. DSC thermograms revealed no melting endotherm, suggesting that the drug is amorphous or molecularly dispersed. Conclusion: NIF and SMX solid dispersions were successfully prepared by spray drying and lyophilization using Soluplus® or PEG 6000. Each polymer enhanced the drug dissolution rate; NIF dissolution rate was improved to a greater extent. Dispersions with PEG 6000 had a faster dissolution rate due to its hydrophilic nature. DSC analysis showed that no crystalline material exists in the

  7. Investigation of the in vitro performance difference of drug-Soluplus® and drug-PEG 6000 dispersions when prepared using spray drying or lyophilization.

    Science.gov (United States)

    Altamimi, Mohammad A; Neau, Steven H

    2017-03-01

    To evaluate the physicochemical and in vitro characteristics of solid dispersions using BCS II model drugs with Soluplus® and one of its component homopolymers, PEG 6000. Nifedipine (NIF) and sulfamethoxazole (SMX) of 99.3% and 99.5% purity, respectively, were selected as BCS II model drugs, such that an improved dissolution rate and concentration in the gastrointestinal tract should increase oral bioavailability. Soluplus® is an amorphous, tri-block, graft co-polymer with polyvinyl caprolactam, polyvinyl acetate, and polyethylene glycol (PCL:PVAc:PEG6000) in the ratio 57:30:13. PEG 6000 (BASF) is a waxy material with melting point of about 60 °C. Solid dispersions were prepared using lyophilization or spray drying techniques. Dissolution study, crystallinity content, and analysis for new chemical bond formation have been used to evaluate the dispersed materials. Although each polymer improved the drug dissolution rate, dissolution from Soluplus® was slower. Enhanced dissolution rates were observed with NIF solid dispersions, but the dissolution profiles were quite different due to the selected technique, polymer, and dissolution medium. For SMX, there was similarity across the dissolution profiles despite the medium, polymer, or applied technique. Each polymer was able to maintain an elevated drug concentration over the three hour duration of the dissolution profile, i.e., supersaturation was supported by the polymer. DSC thermograms revealed no melting endotherm, suggesting that the drug is amorphous or molecularly dispersed. NIF and SMX solid dispersions were successfully prepared by spray drying and lyophilization using Soluplus® or PEG 6000. Each polymer enhanced the drug dissolution rate; NIF dissolution rate was improved to a greater extent. Dispersions with PEG 6000 had a faster dissolution rate due to its hydrophilic nature. DSC analysis showed that no crystalline material exists in the dispersions.

  8. In vivo microdialysis for the investigation of drug levels in the dermis and the effect of barrier perturbation on cutaneous drug penetration. Studies in hairless rats and human subjects.

    Science.gov (United States)

    Benfeldt, E

    1999-01-01

    The thesis opens with review chapters concerning theoretical and practical aspects of the investigation of drug contents in the skin. A discussion of the advantages and limitations of the established methods as well as the relatively new sampling method of microdialysis, which is employed in the experimental section, is given. Factors influencing the barrier function of the normal human skin are described as are the alterations in skin barrier function found in diseased and experimentally barrier perturbed skin. The microdialysis technique consists of introducing an ultra thin, semipermeable tube, a so-called probe, in the dermis. The tube is connected to a precision pump, which provides a steady flow of a tissue-compatible fluid through the probe at a very low flow. Smaller molecules in the tissue, among them the non-protein bound fraction of the drug content in the extracellular fluid, will passively diffuse across the surface of the membrane and thus enter the flow of the perfusate, which is sampled at regular intervals and analysed. Microdialysis is used for the determination of drug levels in the skin after topical as well as systemic drug delivery in the experimental part of the thesis. The method is not applicable to the investigation of all drugs or compounds, as we have shown that it is not feasible to sample highly protein-bound drugs or very lipophilic drugs by microdialysis without further development of the method. The investigation of topical drug administration consists of 2 studies of cutaneous penetration of a model drug, salicylic acid, initially investigated in hairless rats and subsequently in human volunteers. In both studies, barrier perturbation of the skin was undertaken by physical (removal of the stratum corneum by repeated tape stripping) or chemical (treatment with acetone) methods or by provocation of irritative dermatitis (by application of sodium lauryl sulphate, a detergent). Prior to the penetration experiment, the barrier damage

  9. Investigation of β-lactam antibacterial drugs, β-lactamases, and penicillin-binding proteins with fluorescence polarization and anisotropy: a review

    Science.gov (United States)

    Shapiro, Adam B.

    2016-06-01

    This review covers the uses of fluorescence polarization and anisotropy for the investigation of bacterial penicillin binding proteins (PBPs), which are the targets of β-lactam antibacterial drugs (penicillins, cephalosporins, carbapenems, and monobactams), and of the β-lactamase enzymes that destroy these drugs and help to render bacterial pathogens resistant to them. Fluorescence polarization and anisotropy-based methods for quantitation of β-lactam drugs are also reviewed. A particular emphasis is on methods for quantitative measurement of the interactions of β-lactams and other inhibitors with PBPs and β-lactamases.

  10. Should methods of correction for multiple comparisons be applied in pharmacovigilance? Reasoning around an investigation on safety of oral antidiabetic drugs

    OpenAIRE

    Scotti, Lorenza; Romio, Silvana; Ghirardi, Arianna; Arfe, Andrea; Casula, Manuela; Hazell, Lorna; Lapi, Francesco; Catapano, Alberico; Sturkenboom, Miriam; Corrao, Giovanni

    2015-01-01

    textabstractBACKGROUND: In pharmacovigilance, spontaneous reporting databases are devoted to the early detection of adverse event ‘signals’ of marketed drugs. A common limitation of these systems is the wide number of concurrently investigated associations, implying a high probability of generating positive signals simply by chance. However it is not clear if the application of methods aimed to adjust for the multiple testing problems are needed when at least some of the drug-outcome relation...

  11. Investigation into the Effect of Ethylcellulose Viscosity Variation on the Drug Release of Metoprolol Tartrate and Acetaminophen Extended Release Multiparticulates-Part I.

    Science.gov (United States)

    Mehta, R; Teckoe, J; Schoener, C; Workentine, S; Ferrizzi, D; Rajabi-Siahboomi, A

    2016-12-01

    Ethylcellulose is one of the most commonly used polymers to develop reservoir type extended release multiparticulate dosage forms. For multiparticulate extended release dosage forms, the drug release is typically governed by the properties of the barrier membrane coating. The ICH Pharmaceutical Development Guideline (ICH Q8) requires an understanding of the influence of critical material attributes and critical process parameters on the drug release of a pharmaceutical product. Using this understanding, it is possible to develop robust formulations with consistent drug release characteristics. Critical material attributes for ethylcellulose were evaluated, and polymer molecular weight variation (viscosity) was considered to be the most critical attribute that can impact drug release. To investigate the effect of viscosity variation within the manufacturer's specifications of ethylcellulose, extended release multiparticulate formulations of two model drugs, metoprolol tartrate and acetaminophen, were developed using ETHOCEL™ as the rate controlling polymer. Quality by Design (QbD) samples of ETHOCEL Std. 10, 20, and 100 Premium grades representing the low, medium, and high molecular weight (viscosity) material were organically coated onto drug layered multiparticulates to a 15% weight gain (WG). The drug release was found to be similar (f 2 > 50) for both metoprolol tartrate and acetaminophen multiparticulates at different coating weight gains of ethylcellulose, highlighting consistent and robust drug release performance. The use of ETHOCEL QbD samples also serves as a means to develop multiparticulate dosage formulations according to regulatory guidelines.

  12. Investigation and analysis of a drug drug prevalence of periodontal disease personnel of Dalian City%大连市某戒毒所戒毒人员牙周病流行情况的调查及分析

    Institute of Scientific and Technical Information of China (English)

    管奕; 张宇

    2013-01-01

    目的了解某戒毒所吸毒人员牙周状况。方法检查大连市某强制戒毒所正在戒毒人员的牙周病发生情况,分析牙周患病与吸毒时间的关系。结果吸毒者出现牙龈出血、牙结石、牙周袋的比例分别为42%,95%和36%,而且吸毒年限较长的牙周炎区段数明显高于吸毒年限较短者(P<0.01)。结论 提示吸毒可能是口腔牙周疾病发生的高危因素之一。%Objective To investigate the drug users periodontal status. Method for examination of a compulsory detoxification Dalian drug addicts was periodontal disease, periodontal disease and the analysis of the relationship between drug time. Results drug addicts appear gingival bleeding, dental calculus, periodontal pocket respectively 42%, 95% and 36%, and the number of periodontitis drug long was significantly higher than that of drug time shorter (P<0.01). Conclusion: it is suggested that the drug may be one of the risk factors for periodontal disease.

  13. Investigating the ability of nanoparticle-loaded hydroxypropyl methylcellulose and xanthan gum gels to enhance drug penetration into the skin.

    Science.gov (United States)

    Cai, X J; Mesquida, P; Jones, S A

    2016-11-20

    Nanoparticle-loaded topical formulations can disrupt drug aggregation through controlled drug-nanoparticle interactions to enhance topical drug delivery. However, the complex relationship between the drug, nanoparticle and formulation vehicle requires further understanding. The aim of this study was to use nanoparticle-loaded hydroxypropyl methylcellulose (HPMC) and xanthan gum gels to probe how the drug, nanoparticle and formulation vehicle interactions influenced the delivery of an aggregated drug into the skin. Tetracaine was chosen as a model drug. It was loaded into HPMC and xanthan gum gels, and it was presented to porcine skin using infinite and finite dosing protocols. Gel infinite doses showed no important differences in tetracaine skin permeation rate, but HPMC gel finite doses delivered the drug more efficiently (46.99±7.96μg/cm(2)/h) compared to the xanthan gum (1.16±0.14μg/cm(2)/h). Finite doses of the nanoparticle-loaded HPMC gel generated a 10-fold increase in drug flux (109.95±28.63μg/cm(2)/h) compared to the equivalent xanthan gum system (14.19±2.27μg/cm(2)/h). Rheology measurements suggested that the differences in the gels ability to administer the drug into the skin were not a consequence of gel-nanoparticle interactions rather, they were a consequence of the dehydration mediated diffusional restriction imparted on the drug by xanthan gum compared to the viscosity independent interactions of HPMC with the drug.

  14. Investigation of matrix effects in bioanalytical high-performance liquid chromatography/tandem mass spectrometric assays: application to drug discovery.

    Science.gov (United States)

    Mei, Hong; Hsieh, Yunsheng; Nardo, Cymbylene; Xu, Xiaoying; Wang, Shiyong; Ng, Kwokei; Korfmacher, Walter A

    2003-01-01

    A series of studies was performed to investigate some of the causes for matrix effects ('ion suppression' or 'ion enhancement') in bioanalytical high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS) assays. Previous studies have reported that matrix effects are mainly due to endogenous components in biological fluids and are a greater concern for electrospray ionization (ESI) than for atmospheric pressure chemical ionization (APCI). In this report we demonstrate that: (1) matrix effects can also be caused by exogenous materials, such as polymers contained in different brands of plastic tubes, or Li-heparin, a commonly used anticoagulant; (2) matrix effects are not only ionization mode (APCI or ESI) dependent, but also source design (Sciex, Finnigan, Micromass) dependent; and (3) for at least one vendor's design, we found the APCI mode to be more sensitive to matrix effects than the ESI mode. Based on these findings, we have proposed the following simple strategies to avoid matrix effects: (1) select the same brand of plastic tubes for processing and storing plasma samples and spiked plasma standards; (2) avoid using Li-heparin as the anticoagulant; and (3) try switching the ionization mode or switching to different mass spectrometers when matrix effects are encountered. These three strategies have allowed us to use protein precipitation and generic fast LC techniques to generate reliable LC/MS/MS data for the support of pharmacokinetic studies at the early drug discovery stage. Copyright 2002 John Wiley & Sons, Ltd.

  15. A Multidisciplinary Investigation to Determine the Structure and Source of Dimeric Impurities in AMG 517 Drug Substance

    Directory of Open Access Journals (Sweden)

    Maria Victoria Silva Elipe

    2009-01-01

    Full Text Available In the initial scale-up batches of the experimental drug substance AMG 517, a pair of unexpected impurities was observed by HPLC. Analysis of data from initial LC-MS experiments indicated the presence of two dimer-like molecules. One impurity had an additional sulfur atom incorporated into its structure relative to the other impurity. Isolation of the impurities was performed, and further structural elucidation experiments were conducted with high-resolution LC-MS and 2D NMR. The dimeric structures were confirmed, with one of the impurities having an unexpected C-S-C linkage. Based on the synthetic route of AMG 517, it was unlikely that these impurities were generated during the last two steps of the process. Stress studies on the enriched impurities were carried out to further confirm the existence of the C-S-C linkage in the benzothiazole portion of AMG 517. Further investigation revealed that these two dimeric impurities originated from existing impurities in the AMG 517 starting material, N-acetyl benzothiazole. The characterization of these two dimeric impurities allowed for better quality control of new batches of the N-acetyl benzothiazole starting material. As a result, subsequent batches of AMG 517 contained no reportable levels of these two impurities

  16. 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

  17. Investigation of the in vitro toxicological properties of the synthetic cannabimimetic drug CP-47,497-C8

    Energy Technology Data Exchange (ETDEWEB)

    Koller, Verena J., E-mail: verena.koller@meduniwien.ac.at [Institute of Cancer Research, Department of Internal Medicine 1, Comprehensive Cancer Center, Medical University of Vienna, Borschkegasse 8A, 1090 Vienna (Austria); Auwärter, Volker, E-mail: volker.auwaerter@uniklinik-freiburg.de [Institute of Forensic Medicine, University Medical Center Freiburg, Albertstraße 9, 79104 Freiburg (Germany); Grummt, Tamara, E-mail: tamara.grummt@uba.de [German Federal Environmental Agency, Heinrich-Heine-Str., 12, 08645 Bad Elster (Germany); Moosmann, Bjoern, E-mail: bjoern.moosmann@uniklinik-freiburg.de [Institute of Forensic Medicine, University Medical Center Freiburg, Albertstraße 9, 79104 Freiburg (Germany); Mišík, Miroslav, E-mail: miroslav.misik@meduniwien.ac.at [Institute of Cancer Research, Department of Internal Medicine 1, Comprehensive Cancer Center, Medical University of Vienna, Borschkegasse 8A, 1090 Vienna (Austria); Knasmüller, Siegfried, E-mail: siegfried.knasmueller@meduniwien.ac.at [Institute of Cancer Research, Department of Internal Medicine 1, Comprehensive Cancer Center, Medical University of Vienna, Borschkegasse 8A, 1090 Vienna (Austria)

    2014-06-01

    Cannabicyclohexanol (CP-47,497-C8) is a representative of a group of cannabimimetic cyclohexylphenols which is added to herbal mixtures as a cannabis substitute since 2008. Although in the beginning CP-47,497-C8 was the main ingredient of “Spice” and similar products, it was partly replaced by aminoalkylindole-type cannabinoid receptor agonists like JWH-018, JWH-073 or JWH-250, but never completely disappeared from the market. Since information on its toxicological properties is scarce, we investigated the effects of the drug in human derived cell lines. The cytotoxic effects were studied in a panel of assays (SRB, XTT, LDHe and NR tests) in a buccal derived (TR146) and a liver derived (HepG2) cell line. The strongest effects were seen in the two former assays at levels ≥ 7.5 μM indicating that the compound interferes with protein synthesis and causes membrane damage. In additional comet assays, DNA damage was detected at levels ≥ 10 μM. Experiments with lesion specific enzymes showed that these effects are not due to oxidative damage of DNA bases. The negative findings obtained in Salmonella/microsome assays and the positive results of micronucleus tests with the cell lines indicate that the compound does not cause gene mutations but acts on the chromosomal level. In contrast to other synthetic cannabinoids, no indication for estrogenic/antiestrogenic properties was seen in a luciferase assay with bone marrow derived U2-OS cells. In conclusion, our findings show that the drug has only weak cytotoxic properties. However, the induction of chromosomal damage indicates that it may cause adverse effects in users due to its impact on the stability of the genetic material. - Highlights: • We tested the toxic properties of a synthetic cannabinoid. • Acute cytotoxic effects were detected with doses ≥ 7 μM. • No hormonal effects were found. • DNA damage was detected at levels ≥ 10 μM in comet assay and micronucleus tests. • Effects in directly

  18. Drug Addiction Stigma in the Context of Methadone Maintenance Therapy: An Investigation into Understudied Sources of Stigma

    Science.gov (United States)

    Earnshaw, Valerie; Smith, Laramie; Copenhaver, Michael

    2013-01-01

    Experiences of stigma from others among people with a history of drug addiction are understudied in comparison to the strength of stigma associated with drug addiction. Work that has studied these experiences has primarily focused on stigma experienced from healthcare workers specifically even though stigma is often experienced from other sources…

  19. Drug Addiction Stigma in the Context of Methadone Maintenance Therapy: An Investigation into Understudied Sources of Stigma

    Science.gov (United States)

    Earnshaw, Valerie; Smith, Laramie; Copenhaver, Michael

    2013-01-01

    Experiences of stigma from others among people with a history of drug addiction are understudied in comparison to the strength of stigma associated with drug addiction. Work that has studied these experiences has primarily focused on stigma experienced from healthcare workers specifically even though stigma is often experienced from other sources…

  20. Toxicity of Carboxylic Acid-Containing Drugs: The Role of Acyl Migration and CoA Conjugation Investigated.

    Science.gov (United States)

    Lassila, Toni; Hokkanen, Juho; Aatsinki, Sanna-Mari; Mattila, Sampo; Turpeinen, Miia; Tolonen, Ari

    2015-12-21

    Many carboxylic acid-containing drugs are associated with idiosyncratic drug toxicity (IDT), which may be caused by reactive acyl glucuronide metabolites. The rate of acyl migration has been earlier suggested as a predictor of acyl glucuronide reactivity. Additionally, acyl Coenzyme A (CoA) conjugates are known to be reactive. Here, 13 drugs with a carboxylic acid moiety were incubated with human liver microsomes to produce acyl glucuronide conjugates for the determination of acyl glucuronide half-lives by acyl migration and with HepaRG cells to monitor the formation of acyl CoA conjugates, their further conjugate metabolites, and trans-acylation products with glutathione. Additionally, in vitro cytotoxicity and mitochondrial toxicity experiments were performed with HepaRG cells to compare the predictability of toxicity. Clearly, longer acyl glucuronide half-lives were observed for safe drugs compared to drugs that can cause IDT. Correlation between half-lives and toxicity classification increased when "relative half-lives," taking into account the formation of isomeric AG-forms due to acyl migration and eliminating the effect of hydrolysis, were used instead of plain disappearance of the initial 1-O-β-AG-form. Correlation was improved further when a daily dose of the drug was taken into account. CoA and related conjugates were detected primarily for the drugs that have the capability to cause IDT, although some exceptions to this were observed. Cytotoxicity and mitochondrial toxicity did not correlate to drug safety. On the basis of the results, the short relative half-life of the acyl glucuronide (high acyl migration rate), high daily dose and detection of acyl CoA conjugates, or further metabolites derived from acyl CoA together seem to indicate that carboxylic acid-containing drugs have a higher probability to cause drug-induced liver injury (DILI).

  1. The Drug Metabolism and Pharmacokinetics Investigation about Baicalin Effect and Baicalein on Mice U14 Cervical Cancer

    Directory of Open Access Journals (Sweden)

    Zhanzhao Fu

    2015-01-01

    Full Text Available The experiment studies the effect of baicalin and baicalein on mice U14 cervical cancer and its pharmacokinetics in mice. By using different mouse models of cancer treatment program administered and uptake kinetics experiments, tissue distribution experiment, excretion, and metabolism in experimental experiments, we found that baicalin and baicalein can improve immunity and the ability of antioxidation and inhibit the growth of tumor. The absorption of intestinal drug takes place in intestinal tract. Tissue distribution was ideal. Because of the ideal drug distribution, the liver and kidney were protected. Drug was mainly excreted through the feces and bile excretion.

  2. Correlating coating characteristics with the performance of drug-coated balloons--a comparative in vitro investigation of own established hydrogel- and ionic liquid-based coating matrices.

    Directory of Open Access Journals (Sweden)

    Sebastian Kaule

    Full Text Available Drug-coated balloons (DCB, which have emerged as a therapeutic alternative to drug-eluting stents in percutaneous cardiovascular intervention, are well described with regard to clinical efficacy and safety within a number of clinical studies. In vitro studies elucidating the correlation between coating additive and DCB performance are however rare but considered important for the understanding of DCB requirements and the improvement of established DCB. In this regard, we examined three different DCB-systems, which were developed in former studies based on the ionic liquid cetylpyridinium salicylate, the body-own hydrogel hyaluronic acid and the pharmaceutically well-established hydrogel polyvinylpyrrolidone, considering coating morphology, coating thickness, drug-loss, drug-transfer to the vessel wall, residual drug-concentration on the balloon surface and entire drug-load during simulated use in an in vitro vessel model. Moreover, we investigated particle release of the different DCB during simulated use and determined the influence of the three coatings on the mechanical behavior of the balloon catheter. We could show that coating characteristics can be indeed correlated with the performance of DCB. For instance, paclitaxel incorporation in the matrix can reduce the drug wash-off and benefit a high drug transfer. Additionally, a thin coating with a smooth surface and high but delayed solubility can reduce drug wash-off and decrease particle burden. As a result, we suggest that it is very important to characterize DCB in terms of mentioned properties in vitro in addition to their clinical efficacy in order to better understand their function and provide more data for the clinicians to improve the tool of DCB in coronary angioplasty.

  3. Flurbiprofen–antioxidant mutual prodrugs as safer nonsteroidal anti-inflammatory drugs: synthesis, pharmacological investigation, and computational molecular modeling

    Science.gov (United States)

    Ashraf, Zaman; Alamgeer; Kanwal, Munazza; Hassan, Mubashir; Abdullah, Sahar; Waheed, Mamuna; Ahsan, Haseeb; Kim, Song Ja

    2016-01-01

    Flurbiprofen–antioxidant mutual prodrugs were synthesized to reduce the gastrointestinal (GI) effects associated with flurbiprofen. For reducing the GI toxicity, the free carboxylic group (–COOH) was temporarily masked by esterification with phenolic –OH of natural antioxidants vanillin, thymol, umbelliferone, and sesamol. The in vitro hydrolysis of synthesized prodrugs showed that they were stable in buffer solution at pH 1.2, indicating their stability in the stomach. The synthesized prodrugs undergo significant hydrolysis in 80% human plasma and thus release free flurbiprofen. The minimum reversion was observed at pH 1.2, suggesting that prodrugs are less irritating to the stomach than flurbiprofen. The anti-inflammatory, analgesic, antipyretic, and ulcerogenic activities of prodrugs were evaluated. All the synthesized prodrugs significantly (P<0.001) reduced the inflammation against carrageenan and egg albumin-induced paw edema at 4 hours of study. The reduction in the size of the inflamed paw showed that most of the compounds inhibited the later phase of inflammation. The prodrug 2-oxo-2H-chromen-7-yl-2-(2-fluorobiphenyl-4-yl)propanoate (4b) showed significant reduction in paw licking with percentage inhibition of 58%. It also exhibited higher analgesic activity, reducing the number of writhes with a percentage of 75%, whereas flurbiprofen showed 69% inhibition. Antipyretic activity was investigated using brewer’s yeast-induced pyrexia model, and significant (P<0.001) reduction in rectal temperature was shown by all prodrugs at all times of assessment. The results of ulcerogenic activity showed that all prodrugs produced less GI irritation than flurbiprofen. Molecular docking and simulation studies were carried out with cyclooxygenase (COX-1 and COX-2) proteins, and it was observed that our prodrugs have more potential to selectively bind to COX-2 than to COX-1. It is concluded that the synthesized prodrugs have promising pharmacological activities

  4. Experimental strategies for investigating psychostimulant drug actions and prefrontal cortical function in ADHD and related attention disorders.

    Science.gov (United States)

    Agster, Kara L; Clark, Brian D; Gao, Wen-Jun; Shumsky, Jed S; Wang, Huaixing X; Berridge, Craig W; Waterhouse, Barry D

    2011-10-01

    Amphetamine-like psychostimulant drugs have been used for decades to treat a variety of clinical conditions. Methylphenidate (MPH)-Ritalin(R) , a compound that blocks reuptake of synaptically released norepinephrine (NE) and dopamine (DA) in the brain, has been used for more than 30 years in low dose, long-term regimens to treat attention deficit-hyperactive disorder (ADHD) in juveniles, adolescents, and adults. Now, these agents are also becoming increasingly popular among healthy individuals from all walks of life (e.g., military, students) and age groups (teenagers thru senior citizens) to promote wakefulness and improve attention. Although there is agreement regarding the primary biochemical action of MPH, the physiological basis for its efficacy in normal individuals and ADHD patients is lacking. Study of the behavioral and physiological actions of clinically and behaviorally relevant doses of MPH in normal animals provides an opportunity to explore the role of catecholamine transmitters in prefrontal cortical function and attentional processes as they relate to normal operation of brain circuits and ADHD pathology. The goal of ongoing studies has been to: (1) assess the effects of low dose MPH on rodent performance in a well characterized sensory-guided sustained attention task, (2) examine the effects of the same low-dose chronic MPH administration on task-related discharge of prefrontal cortical (PFC) neurons, and (3) investigate the effects of NE and DA on membrane response properties and synaptic transmission in identified subsets of PFC neurons. Combinations of these approaches can be used in adolescent, adult, and aged animals to identify the parameters of cell and neural circuit function that are regulated by MPH and to establish an overarching explanation of how MPH impacts PFC operations from cellular through behavioral functional domains.

  5. An Enzyme- and Serum-free Neural Stem Cell Culture Model for EMT Investigation Suited for Drug Discovery.

    Science.gov (United States)

    Sailer, Martin H M; Sarvepalli, Durga; Brégère, Catherine; Fisch, Urs; Guentchev, Marin; Weller, Michael; Guzman, Raphael; Bettler, Bernhard; Ghosh, Arkasubhra; Hutter, Gregor

    2016-08-23

    Epithelial to mesenchymal transition (EMT) describes the process of epithelium transdifferentiating into mesenchyme. EMT is a fundamental process during embryonic development that also commonly occurs in glioblastoma, the most frequent malignant brain tumor. EMT has also been observed in multiple carcinomas outside the brain including breast cancer, lung cancer, colon cancer, gastric cancer. EMT is centrally linked to malignancy by promoting migration, invasion and metastasis formation. The mechanisms of EMT induction are not fully understood. Here we describe an in vitro system for standardized isolation of cortical neural stem cells (NSCs) and subsequent EMT-induction. This system provides the flexibility to use either single cells or explant culture. In this system, rat or mouse embryonic forebrain NSCs are cultured in a defined medium, devoid of serum and enzymes. The NSCs expressed Olig2 and Sox10, two transcription factors observed in oligodendrocyte precursor cells (OPCs). Using this system, interactions between FGF-, BMP- and TGFβ-signaling involving Zeb1, Zeb2, and Twist2 were observed where TGFβ-activation significantly enhanced cell migration, suggesting a synergistic BMP-/TGFβ-interaction. The results point to a network of FGF-, BMP- and TGFβ-signaling to be involved in EMT induction and maintenance. This model system is relevant to investigate EMT in vitro. It is cost-efficient and shows high reproducibility. It also allows for the comparison of different compounds with respect to their migration responses (quantitative distance measurement), and high-throughput screening of compounds to inhibit or enhance EMT (qualitative measurement). The model is therefore well suited to test drug libraries for substances affecting EMT.

  6. Investigation of Different Lipid Based Materials as Matrices Designed to Control the Release of a Hydrophobic Drug

    OpenAIRE

    Inderbir Singh; Pradeep Kumar; Nisha Rani; Vikas Rana

    2009-01-01

    The present study was designed to evaluate the effect of different hydrophobic materials and their loading level on the release profile of etoricoxib, a model lipophilic drug, from matrix systems. Matrix tablets of the drug were prepared using compritol, precirol, glyceryl monostearate, cetostearyl alcohol and eudragit as release retarding agents by direct compression process. The resulting monolithic tablets were found to have optimum hardness, uniform thickness, high content uniformity and ...

  7. In Vitro Investigation of the Individual Contributions of Ultrasound-Induced Stable and Inertial Cavitation in Targeted Drug Delivery.

    Science.gov (United States)

    Gourevich, Dana; Volovick, Alexander; Dogadkin, Osnat; Wang, Lijun; Mulvana, Helen; Medan, Yoav; Melzer, Andreas; Cochran, Sandy

    2015-07-01

    Ultrasound-mediated targeted drug delivery is a therapeutic modality under development with the potential to treat cancer. Its ability to produce local hyperthermia and cell poration through cavitation non-invasively makes it a candidate to trigger drug delivery. Hyperthermia offers greater potential for control, particularly with magnetic resonance imaging temperature measurement. However, cavitation may offer reduced treatment times, with real-time measurement of ultrasonic spectra indicating drug dose and treatment success. Here, a clinical magnetic resonance imaging-guided focused ultrasound surgery system was used to study ultrasound-mediated targeted drug delivery in vitro. Drug uptake into breast cancer cells in the vicinity of ultrasound contrast agent was correlated with occurrence and quantity of stable and inertial cavitation, classified according to subharmonic spectra. During stable cavitation, intracellular drug uptake increased by a factor up to 3.2 compared with the control. Reported here are the value of cavitation monitoring with a clinical system and its subsequent employment for dose optimization.

  8. Should methods of correction for multiple comparisons be applied in pharmacovigilance? Reasoning around an investigation on safety of oral antidiabetic drugs

    NARCIS (Netherlands)

    L. Scotti (Lorenza); S.A. Romio (Silvana); A. Ghirardi (Arianna); A. Arfe (Andrea); M. Casula (Manuela); L. Hazell (Lorna); F. Lapi (Francesco); A. Catapano (Alberico); M.C.J.M. Sturkenboom (Miriam); G. Corrao (Giovanni)

    2015-01-01

    textabstractBACKGROUND: In pharmacovigilance, spontaneous reporting databases are devoted to the early detection of adverse event ‘signals’ of marketed drugs. A common limitation of these systems is the wide number of concurrently investigated associations, implying a high probability of generating

  9. Investigation of the motion of a viscous fluid in the vitreous cavity induced by eye rotations and implications for drug delivery

    Science.gov (United States)

    Bonfiglio, Andrea; Repetto, Rodolfo; Siggers, Jennifer H.; Stocchino, Alessandro

    2013-03-01

    Intravitreal drug delivery is a commonly used treatment for several retinal diseases. The objective of this research is to characterize and quantify the role of the vitreous humor motion, induced by saccadic movements, on drug transport processes in the vitreous chamber. A Perspex model of the human vitreous chamber was created, and filled with a purely viscous fluid, representing eyes with a liquefied vitreous humor or those containing viscous tamponade fluids. Periodic movements were applied to the model and the resulting three-dimensional (3D) flow fields were measured. Drug delivery within the vitreous chamber was investigated by calculating particle trajectories using integration over time of the experimental velocity fields. The motion of the vitreous humor generated by saccadic eye movements is intrinsically 3D. Advective mass transport largely overcomes molecular diffusive transport and is significantly anisotropic, leading to a much faster drug dispersion than in the case of stationary vitreous humor. Disregarding the effects of vitreous humor motion due to eye movements when predicting the efficiency of drug delivery treatments leads to significant underestimation of the drug transport coefficients, and this, in turn, will lead to significantly erroneous predictions of the concentration levels on the retina.

  10. In Silico Investigations of Chemical Constituents of Clerodendrum colebrookianum in the Anti-Hypertensive Drug Targets: ROCK, ACE, and PDE5.

    Science.gov (United States)

    Arya, Hemant; Syed, Safiulla Basha; Singh, Sorokhaibam Sureshkumar; Ampasala, Dinakar R; Coumar, Mohane Selvaraj

    2017-06-16

    Understanding the molecular mode of action of natural product is a key step for developing drugs from them. In this regard, this study is aimed to understand the molecular-level interactions of chemical constituents of Clerodendrum colebrookianum Walp., with anti-hypertensive drug targets using computational approaches. The plant has ethno-medicinal importance for the treatment of hypertension and reported to show activity against anti-hypertensive drug targets-Rho-associated coiled-coil protein kinase (ROCK), angiotensin-converting enzyme, and phosphodiesterase 5 (PDE5). Docking studies showed that three chemical constituents (acteoside, martinoside, and osmanthuside β6) out of 21 reported from the plant to interact with the anti-hypertensive drug targets with good glide score. In addition, they formed H-bond interactions with the key residues Met156/Met157 of ROCK I/ROCK II and Gln817 of PDE5. Further, molecular dynamics (MD) simulation of protein-ligand complexes suggest that H-bond interactions between acteoside/osmanthuside β6 and Met156/Met157 (ROCK I/ROCK II), acteoside and Gln817 (PDE5) were stable. The present investigation suggests that the anti-hypertensive activity of the plant is due to the interaction of acteoside and osmanthuside β6 with ROCK and PDE5 drug targets. The identified molecular mode of binding of the plant constituents could help to design new drugs to treat hypertension.

  11. In situ investigation of supercritical CO2 assisted impregnation of drugs into a polymer by high pressure FTIR micro-spectroscopy.

    Science.gov (United States)

    Champeau, M; Thomassin, J-M; Jérôme, C; Tassaing, T

    2015-02-01

    An original experimental set-up combining a FTIR micro-spectrometer with a high pressure cell has been built in order to analyze in situ the impregnation of a solute into microscopic polymer samples, such as fibers or films, subjected to supercritical CO2. Thanks to this experimental set-up, key factors governing the impregnation process can be simultaneously followed such as the swelling of the polymeric matrix, the CO2 sorption, the kinetics of impregnation and the drug loading into the matrix. Moreover, the solute/polymer interactions and the speciation of the solute can be analyzed. We have monitored in situ the impregnation of aspirin and ketoprofen into PEO (Polyethylene Oxide) platelets at T = 40 °C and P = 5; 10 and 15 MPa. The kinetics of impregnation of aspirin was quicker than the one of ketoprofen and the final drug loading was also higher in the case of aspirin. Whereas the CO2 sorption and the PEO swelling remain constant when PEO is just subjected to CO2 under isobaric conditions, we noticed that both parameters can increase while the drug impregnates PEO. Coupling these results with DSC measurements, we underlined the plasticizing effect of the drug that also leads to a decrease in the crystallinity of PEO in situ thus favoring the sorption of CO2 molecules into the matrix and the swelling of the matrix. The plasticizing effect increases with the drug loading. Finally, the speciation of drugs was investigated considering the shift of the carboxyl bands of the drugs. Both drugs were found to be mainly homogeneously dispersed into PEO.

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

    Science.gov (United States)

    Zhang, Xingwang; Chen, Guijiang; Zhang, Tianpeng; Ma, Zhiguo; Wu, Baojian

    2014-01-01

    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.

  13. Letermovir and inhibitors of the terminase complex: a promising new class of investigational antiviral drugs against human cytomegalovirus

    Directory of Open Access Journals (Sweden)

    Melendez DP

    2015-08-01

    Full Text Available Dante P Melendez,1,2 Raymund R Razonable1,2 1Division of Infectious Diseases, 2William J von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, MN, USA Abstract: Infection with cytomegalovirus is prevalent in immunosuppressed patients. In solid organ transplant and hematopoietic stem cell transplant recipients, cytomegalovirus infection is associated with high morbidity and preventable mortality. Prevention and treatment of cytomegalovirus with currently approved antiviral drugs is often associated with side effects that sometimes preclude their use. Moreover, cytomegalovirus has developed mutations that confer resistance to standard antiviral drugs. During the last decade, there have been calls to develop novel antiviral drugs that could provide better options for prevention and treatment of cytomegalovirus. Letermovir (AIC246 is a highly specific antiviral drug that is currently undergoing clinical development for the management of cytomegalovirus infection. It acts by inhibiting the viral terminase complex. Letermovir is highly potent in vitro and in vivo against cytomegalovirus. Because of a distinct mechanism of action, it does not exhibit cross-resistance with other antiviral drugs. It is predicted to be active against strains that are resistant to ganciclovir, foscarnet, and cidofovir. To date, early-phase clinical trials suggest a very low incidence of adverse effects. Herein, we present a comprehensive review on letermovir, from its postulated novel mechanism of action to the results of most recent clinical studies. Keywords: cytomegalovirus, letermovir, AIC246, terminase, antivirals, transplantation 

  14. Investigation into in vitro anti-leishmanial combinations of calcium channel blockers and current anti-leishmanial drugs

    Directory of Open Access Journals (Sweden)

    Juliana Quero Reimão

    2011-12-01

    Full Text Available The need for drug combinations to treat visceral leishmaniasis (VL arose because of resistance to antimonials, the toxicity of current treatments and the length of the course of therapy. Calcium channel blockers (CCBs have shown anti-leishmanial activity; therefore their use in combination with standard drugs could provide new alternatives for the treatment of VL. In this work, in vitro isobolograms of Leishmania (Leishmania chagasi using promastigotes or intracellular amastigotes were utilised to identify the interactions between five CCBs and the standard drugs pentamidine, amphotericin B and glucantime. The drug interactions were assessed with a fixed ratio isobologram method and the fractional inhibitory concentrations (FICs, sum of FICs (ΣFICs and the overall mean ΣFIC were calculated for each combination. Graphical isobologram analysis showed that the combination of nimodipine and glucantime was the most promising in amastigotes with an overall mean ΣFIC value of 0.79. Interactions between CCBs and the anti-leishmanial drugs were classified as indifferent according to the overall mean ΣFIC and the isobologram graphic analysis.

  15. Investigation of specificity ensuring of quality of biological medicinal products on example of drugs Cortexin and Retinalamin

    Directory of Open Access Journals (Sweden)

    N. O. Vetiutneva

    2013-06-01

    consists of the following stages: preparing of the solution for bottling, sterilizing filtration, washing and sterilizing of the bottles, aseptic filling, freeze drying and plugging, seaming, continuous monitoring in bulk. After getting the quality certificate and declaration of conformity products are transferred to the storage place for finished products. The specificity of differences between biological medical products and synthetic medicines was investigated. Stages of ensuring of the quality of biological medicinal products with considering of particular qualities of the critical points were considered - the special conditions in the manufacturing process, temperature monitoring, systems and procedures of ensuring in quality during transportation, storage. The main stages of ensuring of quality were studied on the example of original drugs Cortexin and Retinalamin in the chain from production to sale.

  16. Impulsion of nanoparticles as a drug carrier for the theoretical investigation of stenosed arteries with induced magnetic effects

    Science.gov (United States)

    Nadeem, S.; Ijaz, S.

    2016-07-01

    In this paper hemodynamics of stenosis are discussed to predict effect of atherosclerosis by means of mathematical models in the presence of uniform transverse magnetic field. The analysis is carried out using silver and copper nanoparticles as a drug carrier. Exact solution for the fluid temperature, velocity, axial induced magnetic field and current density distribution are obtained under mild stenosis approximation. The results indicate that with an increase in the concentration of nanoparticle hemodynamics effects of stenosis reduces throughout the inclined composite stenosed arteries. The considered analysis also summarizes that the drug silver nanoparticles is more efficient to reduce hemodynamics of stenosis when compare to the drug copper nanoparticle. In future this model could be helpful to predict important properties in some biomedical applications.

  17. Glia and epilepsy: experimental investigation of antiepileptic drugs in an astroglia/microglia co-culture model of inflammation.

    Science.gov (United States)

    Dambach, Hannes; Hinkerohe, Daniel; Prochnow, Nora; Stienen, Martin N; Moinfar, Zahra; Haase, Claus G; Hufnagel, Andreas; Faustmann, Pedro M

    2014-01-01

    The contribution of glial cells, mainly astrocytes and microglia, to the pathophysiology of epilepsy is increasingly appreciated. Glia play a pivotal role in the initiation and maintenance of the central nervous system (CNS) immune response and neuronal metabolic and trophic supply. Recent clinical and experimental evidence suggests a direct relationship between epileptic activity and CNS inflammation, which is characterized by accumulation, activation, and proliferation of microglia and astrocytes. Concomitant glia-mediated mechanisms of action of several antiepileptic drugs (AEDs) have been proposed. However, their direct effects on glial cells have been rarely investigated. We aimed to investigate the effect of commonly used AEDs on glial viability, the gap junctional network, the microglial activation, and cytokine expression in an in vitro astroglia/microglia co-culture model. Primary astrocytic cultures were prepared from brains of postnatal (P0-P2) Wistar rats and co-cultured with a physiologic amount of 5%, as well as 30% microglia in order to mimic inflammatory conditions. Co-cultures were treated with valproic acid (VPA), carbamazepine (CBZ), phenytoin (PHE), and gabapentin (GBT). Viability and proliferation were measured using the tetrazolium (MTT) assay. The microglial activation state was determined by immunocytochemical labeling. The astroglial connexin 43 (Cx43) expression was measured by Western blot analysis. The transforming growth factor-β1 (TGF-β1) and tumor necrosis factor-α (TNF-α) cytokine levels were measured by the quantitative sandwich enzyme immunosorbent assay (ELISA). Astrocytes, co-cultured with 5% microglia (M5 co-cultures), showed a dose-dependent, significant reduction in glial viability after incubation with PHE and CBZ. Furthermore, VPA led to highly significant microglial activation at all doses examined. The antiinflammatory cytokine TGF-β1 release was induced by high doses of GBT and PHE. Astrocytes co-cultured with 30

  18. Impulsion of nanoparticles as a drug carrier for the theoretical investigation of stenosed arteries with induced magnetic effects

    Energy Technology Data Exchange (ETDEWEB)

    Nadeem, S.; Ijaz, S., E-mail: shagufta.me2011@yahoo.com

    2016-07-15

    In this paper hemodynamics of stenosis are discussed to predict effect of atherosclerosis by means of mathematical models in the presence of uniform transverse magnetic field. The analysis is carried out using silver and copper nanoparticles as a drug carrier. Exact solution for the fluid temperature, velocity, axial induced magnetic field and current density distribution are obtained under mild stenosis approximation. The results indicate that with an increase in the concentration of nanoparticle hemodynamics effects of stenosis reduces throughout the inclined composite stenosed arteries. The considered analysis also summarizes that the drug silver nanoparticles is more efficient to reduce hemodynamics of stenosis when compare to the drug copper nanoparticle. In future this model could be helpful to predict important properties in some biomedical applications. - Highlights: • The contribution of copper and silver nanoparticles as drug carrier reveals that they are important to reduce hemodynamic of stenosis. • The heat is dissipated throughout the considered inclined artery with an increase in the nanoparticle volume fraction. • The stress on the wall of inclined arteries decreases with an increase in the magnetic Reynolds number and Strommers number.

  19. A Comprehensive Spectroscopic and Computational Investigation to Probe the Interaction of Antineoplastic Drug Nordihydroguaiaretic Acid with Serum Albumins.

    Directory of Open Access Journals (Sweden)

    Saima Nusrat

    Full Text Available Exogenous drugs that are used as antidote against chemotheray, inflammation or viral infection, gets absorbed and interacts reversibly to the major serum transport protein i.e. albumins, upon entering the circulatory system. To have a structural guideline in the rational drug designing and in the synthesis of drugs with greater efficacy, the binding mechanism of an antineoplastic and anti-inflammatory drug Nordihydroguaiaretic acid (NDGA with human and bovine serum albumins (HSA & BSA were examined by spectroscopic and computational methods. NDGA binds to site II of HSA with binding constant (Kb ~105 M-1 and free energy (ΔG ~ -7.5 kcal.mol-1. It also binds at site II of BSA but with lesser binding affinity (Kb ~105 M-1 and ΔG ~ -6.5 kcal.mol-1. The negative value of ΔG, ΔH and ΔS for both the albumins at three different temperatures confirmed that the complex formation process between albumins and NDGA is spontaneous and exothermic. Furthermore, hydrogen bonds and hydrophobic interactions are the main forces involved in complex formation of NDGA with both the albumins as evaluated from fluorescence and molecular docking results. Binding of NDGA to both the albumins alter the conformation and causes minor change in the secondary structure of proteins as indicated by the CD spectra.

  20. Investigating how the attributes of self-associated drug complexes influence the passive transport of molecules through biological membranes.

    Science.gov (United States)

    Inacio, R; Barlow, D; Kong, X; Keeble, J; Jones, S A

    2016-05-01

    Relatively little is known about how drug self-association influences absorption into the human body. This study presented two hydrophobic membranes with a series of solutions containing different types of tetracaine aggregates with the aim of understanding how the attributes of supramolecular aggregate formation influenced passive membrane transport. The data showed that aqueous solutions of the unprotonated form of tetracaine displayed a significantly higher (ptransport compared to solutions with mixtures of the unprotonated and protonated drug microspecies (e.g. transport through the skin was 0.96±0.31μgcm(-2)min(-1) and 1.59±0.26μgcm(-2)min(-1) respectively). However, despite an enhanced rate of drug transport and a better membrane partitioning the unionised molecules showed a significantly longer (ptransport studies showed that larger tetracaine aggregates with smaller surface charge gave rise to the longer lag times. These large aggregates demonstrated more extensive intermolecular bonding and therefore, it was suggest that it was the enhanced propensity of the unionised species to form tightly bound drug aggregates that caused the delay in the membrane penetration.

  1. The draft genome of Mycobacterium aurum, a potential model organism for investigating drugs against Mycobacterium tuberculosis and Mycobacterium leprae

    KAUST Repository

    Phelan, Jody

    2015-06-04

    Mycobacterium aurum (M. aurum) is an environmental mycobacteria that has previously been used in studies of anti-mycobacterial drugs due to its fast growth rate and low pathogenicity. The M. aurum genome has been sequenced and assembled into 46 contigs, with a total length of 6.02 Mb containing 5684 annotated protein-coding genes. A phylogenetic analysis using whole genome alignments positioned M. aurum close to Mycobacterium vaccae and Mycobacterium vanbaalenii, within a clade related to fast-growing mycobacteria. Large-scale genomic rearrangements were identified by comparing the M. aurum genome to those of Mycobacterium tuberculosis and Mycobacterium leprae. M. aurum orthologous genes implicated in resistance to anti-tuberculosis drugs in M. tuberculosis were observed. The sequence identity at the DNA level varied from 68.6% for pncA (pyrazinamide drug-related) to 96.2% for rrs (streptomycin, capreomycin). We observed two homologous genes encoding the catalase-peroxidase enzyme (katG) that is associated with resistance to isoniazid. Similarly, two embB homologues were identified in the M. aurum genome. In addition to describing for the first time the genome of M. aurum, this work provides a resource to aid the use of M. aurum in studies to develop improved drugs for the pathogenic mycobacteria M. tuberculosis and M. leprae.

  2. 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

  3. Induced pluripotent stem cells reveal functional differences between drugs currently investigated in patients with hutchinson-gilford progeria syndrome.

    Science.gov (United States)

    Blondel, Sophie; Jaskowiak, Anne-Laure; Egesipe, Anne-Laure; Le Corf, Amelie; Navarro, Claire; Cordette, Véronique; Martinat, Cécile; Laabi, Yacine; Djabali, Karima; de Sandre-Giovannoli, Annachiara; Levy, Nicolas; Peschanski, Marc; Nissan, Xavier

    2014-04-01

    Hutchinson-Gilford progeria syndrome is a rare congenital disease characterized by premature aging in children. Identification of the mutation and related molecular mechanisms has rapidly led to independent clinical trials testing different marketed drugs with a preclinically documented impact on those mechanisms. However, the extensive functional effects of those drugs remain essentially unexplored. We have undertaken a systematic comparative study of the three main treatments currently administered or proposed to progeria-affected children, namely, a farnesyltransferase inhibitor, the combination of an aminobisphosphonate and a statin (zoledronate and pravastatin), and the macrolide antibiotic rapamycin. This work was based on the assumption that mesodermal stem cells, which are derived from Hutchinson-Gilford progeria syndrome-induced pluripotent stem cells expressing major defects associated with the disease, may be instrumental to revealing such effects. Whereas all three treatments significantly improved misshapen cell nuclei typically associated with progeria, differences were observed in terms of functional improvement in prelamin A farnesylation, progerin expression, defective cell proliferation, premature osteogenic differentiation, and ATP production. Finally, we have evaluated the effect of the different drug combinations on this cellular model. This study revealed no additional benefit compared with single-drug treatments, whereas a cytostatic effect equivalent to that of a farnesyltransferase inhibitor alone was systematically observed. Altogether, these results reveal the complexity of the modes of action of different drugs, even when they have been selected on the basis of a similar mechanistic hypothesis, and underscore the use of induced pluripotent stem cell derivatives as a critical and powerful tool for standardized, comparative pharmacological studies.

  4. Investigation and research of drug addicts in Hengyang city%衡阳市吸毒现状调查与研究

    Institute of Scientific and Technical Information of China (English)

    熊平

    2001-01-01

    The author had investigation 227 cases of drug addict in labor camp of Hengyang city.The survey showed some factors were high related to drug addict such as:younger age、low education degree、dependence of drug caused by therapy、family factor、enterprise wasn't running smoothly etc.Therefore,hitting out against culturing、producing and selling narcotic drugs severely、enforcing education of prohibition necrotic and controlling malign factors of society and psychology are effective measures to prevent taking narcotic drugs.%本文对衡阳市劳教所戒毒大队227名吸毒者进行了社会学调查。结果表明:年龄小、受教育程度低、对毒品危害性认识不足、因疾病治疗而致药物性依赖、家庭原因、事业不顺等因素与吸毒密切相关。所以加强禁毒宣传教育,严厉打击种毒、制毒、贩毒,以及控制不良的社会、心理因素是预防吸毒的有效措施。

  5. Investigation of the uptake of drugs, carcinogens and mutagens by individual mammalian cells using a scanning proton microprobe

    Science.gov (United States)

    Cholewa, M.; Turnbull, I. F.; Legge, G. J. F.; Weigold, H.; Marcuccio, S. M.; Holan, G.; Tomlinson, E.; Wright, P. J.; Dillon, C. T.; Lay, P. A.; Bonin, A. M.

    1995-09-01

    The use of micro-PIXE [1] in measuring the quantitative uptake of drugs containing metal atoms by individual Vero cells (African green monkey kidney cell line) and V79 Chinese hamster lung cells is demonstrated. One class of drugs, heteropolytungstates, which are being assessed for activity against the HIV virus, were studied using Vero cells. The cellular uptake of a series of chromium compounds, including carcinogens and mutagens, in which the metal oxidation state was either (III), (V) or (VI), was measured using V79 cells. It was found that, unlike any other techniques, scanning proton microprobe (SPM) offers both the sensitivity and spatial resolution to carry out unicellular analysis. The use of cultured cell lines in these analyses was shown to have distinct advantages over cells such as peripheral blood lymphocytes (PBLs).

  6. The multiple truths about crystal meth among young people entrenched in an urban drug scene: a longitudinal ethnographic investigation.

    Science.gov (United States)

    Fast, Danya; Kerr, Thomas; Wood, Evan; Small, Will

    2014-06-01

    Transitions into more harmful forms of illicit drug use among youth have been identified as important foci for research and intervention. In settings around the world, the transition to crystal methamphetamine (meth) use among youth is considered a particularly dangerous and growing problem. Epidemiological evidence suggests that, particularly among young, street-involved populations, meth use is associated with numerous sex- and drug-related "risks behaviors" and negative health outcomes. Relatively few studies, however, have documented how youth themselves understand, experience and script meth use over time. From 2008 to 2012, we conducted over 100 in-depth interviews with 75 street-entrenched youth in Vancouver, Canada, as well as ongoing ethnographic fieldwork, in order to examine youth's understandings and experiences of meth use in the context of an urban drug scene. Our findings revealed positive understandings and experiences of meth in relation to other forms of drug addiction and unaddressed mental health issues. Youth were simultaneously aware of the numerous health-related harms and social costs associated with heavy meth use. Over time, positive understandings of meth may become entirely contradictory to a lived reality in which escalating meth use is a factor in further marginalizing youth, although this may not lead to cessation of use. Recognition of these multiple truths about meth, and the social structural contexts that shape the scripting of meth use among youth in particular settings, may help us to move beyond moralizing debates about how to best educate youth on the "risks" associated with meth, and towards interventions that are congruent with youth's lived experiences and needs across the lifecourse.

  7. Pharmaceutical characterization of novel tenofovir liposomal formulations for enhanced oral drug delivery: in vitro pharmaceutics and Caco-2 permeability investigations

    OpenAIRE

    Spinks, Crystal; Zidan, Ahmed; Khan, Mansoor; Habib, Muhammad; Faustino,Patrick

    2017-01-01

    Crystal B Spinks,1 Ahmed S Zidan,2,3 Mansoor A Khan,4 Muhammad J Habib,1 Patrick J Faustino2 1Department of Pharmaceutical Sciences, School of Pharmacy, Howard University, Washington, DC, 2Division of Product Quality Research, Office of Pharmaceutical Quality, Food and Drug Administration, Silver Spring, MD, USA; 3Faculty of Pharmacy, Zagazig University, Zagazig, Egypt; 4Irma Lerma Rangel College of Pharmacy, Texas A&M Health Science Center, College Station, TX, USA Abstract: Tenofovi...

  8. Modulation of histamine release by fatty acids. A new in vitro model investigating adverse drug reactions in various species

    OpenAIRE

    Ennis, M.; Lorenz, Wilfried

    1985-01-01

    Histamine release caused by drugs and/or their solvents is a well known phenomenon. In this study, both in vivo (anaesthetized and conscious dogs) and in vitro (isolated rat peritoneal, human and guinea-pig lung mast cells) models were used. Cremophor E1 and six derivatives of 12-hydroxystearic acid were compared for their histamine releasing abilities. Although the three types of isolated mast cells responded similarly, histamine release being observed with DH (the diester of 12-hydroxystear...

  9. The anatomy of risk: a quantitative investigation into injection drug users' taxonomy of risk attitudes and perceptions.

    Science.gov (United States)

    Marsch, Lisa A; Bickel, Warren K; Badger, Gary J; Quesnel, Kimberly J

    2007-04-01

    The authors report on the first study to use the systematic quantitative methods of the psychometric paradigm of risk analysis to examine risk perceptions among substance abusers. Fifty opioid-dependent injection drug users (IDUs) and 50 matched, control individuals completed a series of measures to provide quantitative representations of risk perceptions about 53 risk-laden items (including activities, substances, technologies, and diseases). Results indicated that risk perceptions of IDUs and controls were highly correlated on many items; however, IDUs perceived several items, such as hepatitis, HIV, handguns, and unprotected sex, as markedly more risky. IDUs also perceived both themselves and others as having greater risk of contracting hepatitis and HIV. IDUs wanted significantly reduced regulation of drugs, including prescription drugs, heroin, valium, and barbiturates. Factor analyses conducted to understand how risk ratings related to various characteristics that have been shown to influence risk perception revealed 3 factors that account for approximately 80% of the variability in risk perception across groups: Factor 1, related to the severity of the risk; Factor 2, related to the certainty of the risk; and Factor 3, related to the immediacy of the risk. However, IDUs more strongly associated the extent to which they were personally affected by a risk item and the extent to which the risk affected fewer or more people to Factor 1, whereas control participants more strongly associated these characteristics with Factor 2. Identifying improved methodologies for evaluating the risk perceptions of IDUs may be of considerable utility in understanding their high-risk behavior.

  10. Physicochemical characterisation and investigation of the bonding mechanisms of API-titanate nanotube composites as new drug carrier systems.

    Science.gov (United States)

    Sipos, Barbara; Pintye-Hódi, Klára; Kónya, Zoltán; Kelemen, András; Regdon, Géza; Sovány, Tamás

    2017-02-25

    Titanate nanotube (TNT) has recently been explored as a new carrier material for active pharmaceutical ingredients (API). The aim of the present work was to reveal the physicochemical properties of API-TNT composites, focusing on the interactions between the TNTs and the incorporated APIs. Drugs belonging to different Biopharmaceutical Classification System (BCS) classes were loaded into TNTs: diltiazem hydrochloride (BCS I.), diclofenac sodium (BCS II.), atenolol (BCS III.) and hydrochlorothiazide (BCS IV.). Experimental results demonstrated that it is feasible for spiral cross-sectioned titanate nanotubes to carry drugs and maintain their bioactivity. The structural properties of the composites were characterized by a range of analytical techniques, including FT-IR, DSC, TG-MS, etc. The interactions between APIs and TNTs were identified as electrostatic attractions, mainly dominated by hydrogen bonds. Based on the results, it can be stated that the strength of the association depends on the hydrogen donor strength of the API. The drug release of incorporated APIs was evaluated from compressed tablets and compared to that of pure APIs. Differences noticed in the dissolution profiles due to incorporation showed a correlation with the strength of interactions between the APIs and the TNTs observed in the above analytical studies. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Investigation of Drug use in 166 Patients with Cerebral Infarction%166例脑梗塞住院患者用药情况分析

    Institute of Scientific and Technical Information of China (English)

    丁继岩

    2015-01-01

    Objective The use of drugs in patients with cerebral infarction was investigated, so as to provide guidance for the rational use of drugs. Methods The clinical data of 166 cases of hospitalized patients with cerebral infarction were ret-rospectively analyzed and statistics, in order to understand the patient's clinical use. Results During hospitalization, patients take basic symptomatic treatment and comprehensive treatment methods, the use of drugs dehydration drugs, optimization cerebrovascular circulation drugs, thrombolytic drugs, anti-platelet drugs and anticoagulants, improve brain metabolism, im-prove awareness and nootropic drugs; 140 cases were cured, improved and was discharged 13 cases, 2 cases were trans-ferred, but the hospital did not cure those four cases, 7 deaths. Conclusion To ensure that the effect of the treatment of dis-eases of cerebral infarction, clinicians need to achieve rational use of drugs, medication safety, reduce the incidence of ad-verse reactions.%目的 对脑梗塞住院病人的用药情况展开调查,以便为此病的合理用药提供指导意见.方法 对166例脑梗塞住院患者的临床资料进行回顾性分析,以了解患者的临床用药情况. 结果 在住院治疗期间,患者采取基础对症治疗与综合治疗的方法,所用药物有脱水药物、优化脑血管循环药物、溶栓药物、抗血小板聚集药物与抗凝药物、改善脑代谢、改善意识和促智药物等;140例治愈,好转且出院者13例,转院者2例,并未治愈但出院者4例,7例死亡. 结论为确保脑梗塞疾病治疗的效果,临床医生需做到合理用药、安全用药,降低不良反应的发生.

  12. Thyroid organotypic rat and human cultures used to investigate drug effects on thyroid function, hormone synthesis and release pathways

    Energy Technology Data Exchange (ETDEWEB)

    Vickers, Alison E.M., E-mail: vickers_alison@allergan.com [Drug Safety Evaluation, Allergan Inc., 2525 Dupont Dr, Irvine CA 92612 (United States); Heale, Jason; Sinclair, John R.; Morris, Stephen; Rowe, Josh M. [Drug Safety Evaluation, Allergan Inc., 2525 Dupont Dr, Irvine CA 92612 (United States); Fisher, Robyn L. [Vitron Inc., Tucson, AZ (United States)

    2012-04-01

    Drug induced thyroid effects were evaluated in organotypic models utilizing either a rat thyroid lobe or human thyroid slices to compare rodent and human response. An inhibition of thyroid peroxidase (TPO) function led to a perturbation in the expression of key genes in thyroid hormone synthesis and release pathways. The clinically used thiourea drugs, methimazole (MMI) and 6-n-propyl-2-thioruacil (PTU), were used to evaluate thyroid drug response in these models. Inhibition of TPO occurred early as shown in rat thyroid lobes (2 h) and was sustained in both rat (24–48 h) and human (24 h) with ≥ 10 μM MMI. Thyroid from rats treated with single doses of MMI (30–1000 mg/kg) exhibited sustained TPO inhibition at 48 h. The MMI in vivo thyroid concentrations were comparable to the culture concentrations (∼ 15–84 μM), thus demonstrating a close correlation between in vivo and ex vivo thyroid effects. A compensatory response to TPO inhibition was demonstrated in the rat thyroid lobe with significant up-regulation of genes involved in the pathway of thyroid hormone synthesis (Tpo, Dio1, Slc5a5, Tg, Tshr) and the megalin release pathway (Lrp2) by 24 h with MMI (≥ 10 μM) and PTU (100 μM). Similarly, thyroid from the rat in vivo study exhibited an up-regulation of Dio1, Slc5a5, Lrp2, and Tshr. In human thyroid slices, there were few gene expression changes (Slc5a5, ∼ 2-fold) and only at higher MMI concentrations (≥ 1500 μM, 24 h). Extended exposure (48 h) resulted in up-regulation of Tpo, Dio1 and Lrp2, along with Slc5a5 and Tshr. In summary, TPO was inhibited by similar MMI concentrations in rat and human tissue, however an increased sensitivity to drug treatment in rat is indicated by the up-regulation of thyroid hormone synthesis and release gene pathways at concentrations found not to affect human tissue. -- Highlights: ► Novel model of rat thyroid or human thyroid slices to evaluate pathways of injury. ► TPO inhibition by MMI or PTU altered

  13. Investigation and Application of a New Passive Sampling Technique for in Situ Monitoring of Illicit Drugs in Waste Waters and Rivers.

    Science.gov (United States)

    Guo, Changsheng; Zhang, Tingting; Hou, Song; Lv, Jiapei; Zhang, Yuan; Wu, Fengchang; Hua, Zhendong; Meng, Wei; Zhang, Hao; Xu, Jian

    2017-08-15

    Illicit drugs constitute a class of emerging contaminants that has been drawing significant concern due to its potent pharmacological and biological activities. In this study, an in situ passive sampling approach that uses diffusive gradients in thin films (DGT) was successfully tested for measuring ketamine (KET), methamphetamine (METH), and amphetamine (AMP) in water. The diffusion coefficients of KET, METH, and AMP in diffusive gel were (8.13 ± 0.12) × 10(-6), (8.55 ± 0.14) × 10(-6), and (7.72 ± 0.18) × 10(-6) cm(2) s(-1) at 22 °C, respectively. The capacities of an XAD binding gel for KET, METH, and AMP were 92, 57, and 45 μg per binding gel disc, which were suitable for long-term environmental monitoring. The DGT measurement of these drugs was not influenced by the pH (4 to 9) and the ionic strength (0.001 M - 0.1 M) and unaffected by the water flow, demonstrating the effectiveness of the XAD-based DGT for the in situ monitoring of illicit drugs. DGT samplers were deployed in a WWTP influent and natural rivers in Beijing, China. The ng L(-1) levels of the drugs were high in the wastewater influent and low in river waters, with an insignificant fluctuation during the seven-day monitoring. The DGT-measured concentrations were comparable to the average concentrations determined by SPE method, which suggested that the average data measured by DGT could be substituted for high-frequency grab sampling. This study has demonstrated systematically for the first time that DGT is effective and accurate for monitoring illicit drugs in wastewater and surface waters, and provides a powerful tool to investigating the presence, transport, and environmental behaviors of these drugs in the aquatic ecosystem.

  14. Serious and actionable risks, plus disclosure: Investigating an alternative approach for presenting risk information in prescription drug television advertisements.

    Science.gov (United States)

    Betts, Kevin R; Boudewyns, Vanessa; Aikin, Kathryn J; Squire, Claudia; Dolina, Suzanne; Hayes, Jennifer J; Southwell, Brian G

    2017-08-02

    Broadcast direct-to-consumer (DTC) prescription drug ads that present product claims are required to also present the product's major risks. Debate exists regarding how much information should be included in these major risk statements. Some argue that such statements expose people to unnecessary amounts of information, while others argue that they leave out important information. Examine the impact of type of risk statement (unedited versus serious and actionable risks only) and a disclosure indicating that not all risks are presented on consumers' ability to remember the important risks and benefits of a drug following exposure to a DTC television advertisement (ad). Risk and benefit perceptions, ad-prompted actions, recognition of the disclosure statement, and evaluations of both the disclosure and risk statement were also examined. A web-based experiment was conducted in which US adults who self-reported as having depression (N = 500), insomnia (N = 500), or high cholesterol (N = 500) were randomly assigned to view one of four versions of the television ad, and then complete a questionnaire. The type of risk statement had a significant effect on risk recall and recognition, benefit recognition, perceived risk severity (depression condition only), and perceived benefit magnitude (high cholesterol condition only). Disclosure recognition (using bias-corrected scores) ranged from 63% to 70% across the three illness samples. The revised risk statement improved overall processing of the television ad, as evidenced by improved risk recall and recognition and improved benefit recognition. Further, the presence of the disclosure did not adversely affect consumers' processing of drug risk and benefit information. Therefore, limiting the risks presented in DTC television ads and including a disclosure alerting consumers that not all risks are presented may be an effective strategy for communicating product risks. Published by Elsevier Inc.

  15. Development of an in vitro assay for the investigation of metabolism-induced drug hepatotoxicity

    DEFF Research Database (Denmark)

    Otto, Marie; Hansen, Steen Honore'; Dalgaard, L.

    2008-01-01

    the cytotoxicity of diclofenac was increased by S9 enzymes when an NADPH regenerating system was used. The increased toxicity was NADPH dependent. Reactive drug metabolites of diclofenac, formed by NADPH-dependent metabolism, were identified by LC-MS. Furthermore, an increase in toxicity, not related to enzymatic...... activity but to G6P, was observed for diclofenac and minocycline. Tacrine and amodiaquine displayed decreased toxicity with S9-mix, and carbamazepine, phenytoin, bromfenac and troglitazone were nontoxic at all tested concentrations, with or without S9-mix. The results show that this method...

  16. Investigation and analysis of drug adverse reactions%抗菌药物不良反应调查分析

    Institute of Scientific and Technical Information of China (English)

    梁江萍; 方丽华; 洪帆

    2013-01-01

    OBJECTIVE To guide the rational use of antimicrobial drugs in the hospital by analyzing the characteristics of antibiotics adverse reactions. METHODS A total of 197 antibiotics adverse reaction reports were retrospectively analyzed. RESULTS The incidence of antibiotics adverse reactions was 52. 3% of the male patients. 47. 7% of the female patients, 23. 9% of the old, and 17. 3% of the children. Cephalosporins, quinolones, and penicillin were the top three antibiotics for the incidence of adverse reactions, accounting for 34. 5% , 22. 3% , and 12. 7%, respectively. The duration of adverse drug reactions with less than one day accounted for 41. 6% s 180 cases of drug adverse reactions occurred during the injection administration, accounting for 91. 3%; the antibiotic adverse reactions mainly occurred in internal medicine department, accounting for 25. 4%. CONCLUSION It is necessary to the strengthen the antibiotic administration and improve the level of drug application so as to prevent the adverse reactions.%目的 通过分析抗菌药物不良反应的特征,指导临床合理运用抗菌药物.方法 对197例抗菌药物不良反应进行回顾性分析.结果 男性103例,占52.3%,女性94例,占47.7%,老人和小儿最多,分别占23.9%和17.3%;其中头孢菌素类、喹诺酮类和青霉素类最多,分别占34.5%,22.3%和12.7%;不良反应出现的时间以<1d为主,占41.6%;注射给药途径最易发生共180例,占91.3%;以内科发生不良应最多,占25.4%.结论 要加强抗菌药物管理,提高抗菌药物运用水平,防止不良反应发生.

  17. Microdialysis sampling for investigations of bioavailability and bioequivalence of topically administered drugs: current state and future perspectives

    DEFF Research Database (Denmark)

    Holmgaard, R; Nielsen, J B; Benfeldt, E

    2010-01-01

    by skin disease or barrier perturbation. A comparison between MD and other tissue sampling techniques reveals the advantages and limitations of the method. Subsequently, an in-depth discussion of the application of MD for the evaluation of bioavailability and bioequivalence of topical formulations...... is concluded by the current regulatory point of view. The future perspective includes further expansion and validation of the use of MD in the experimental and clinical setting as well as in the optimization of the method for regulatory purposes, i.e. the commercialization of bioequivalent, generic drug...

  18. Functionalized biocompatible polyelectrolyte multilayers for drug delivery: In situ investigation of mechanical properties by dissipative quartz crystal microbalance

    Energy Technology Data Exchange (ETDEWEB)

    Habibi, Neda [Department of Informatics, Bioengineering, Robotics and Systems Engineering, University of Genova, Genova (Italy); Nanotechnology and Advanced Material Institute, Isfahan University of Technology, Isfahan (Iran, Islamic Republic of); Pastorino, Laura, E-mail: laura.pastorino@unige.it [Department of Informatics, Bioengineering, Robotics and Systems Engineering, University of Genova, Genova (Italy); Ruggiero, Carmelina [Department of Informatics, Bioengineering, Robotics and Systems Engineering, University of Genova, Genova (Italy)

    2014-02-01

    Nanostructured polymeric capsules have been applied in different fields, and specifically are regarded as promising for smart drug delivery applications. The physical–chemical and mechanical properties, and thus the permeability of the polyelectrolyte multilayer shell, play an important role in efficient delivery. Quartz crystal microbalance working in liquid has been used for the characterization of the buildup process and of the viscoelastic properties of biocompatible multilayers and of their functionalization by S-layer proteins. Optical and scanning electron microscopy have been used for the morphological characterization of nanostructured capsules obtained at physiological conditions by the assembly of the characterized multilayers onto spherical cores and by their subsequent removal. The proposed functionalized biocompatible capsules can be regarded as promising candidates for smart drug delivery applications. - Graphical abstract: SEM image of nanostructured polymeric capsules made by 4 bilayers of collagen/alginate at pH 7.4. - Highlights: • Build-up of biocompatible multilayers and functionalization by S-layer proteins • Characterization of multilayer growth and mechanical properties by QCM • Fabrication of S-layer functionalized biocompatible capsules.

  19. Investigating the Use of Polymeric Binders in Twin Screw Melt Granulation Process for Improving Compactibility of Drugs.

    Science.gov (United States)

    Batra, Amol; Desai, Dipen; Serajuddin, Abu T M

    2017-01-01

    Traditionally, the melt granulation for pharmaceutical products was performed at low temperature (twin screw extruder where the processing temperature could be increased to as high as 180°C and polymers with high Tg could be used as binders. In this study, different polymeric binders were screened for their suitability in improving compactibility of 2 drugs, metformin hydrochloride and acetaminophen, by twin screw melt granulation. Processing temperatures for the 2 drugs were set at 180°C and 130°C, respectively. Screw configuration, screw speed, and feed rate were optimized such that all polymeric binders used produced granules. Several hydroxypropyl cellulose, hydroxypropyl methylcellulose, polyvinylpyrrolidone, and methacrylate-based polymers, including Klucel(®) EXF, Eudragit(®) EPO, and Soluplus(®), demonstrated good tablet tensile strength (>2 MPa) when granules were produced using only 10% wt/wt polymer concentration. Certain polymers provided acceptable compactibility even at 5% wt/wt. Thus, twin screw melt granulation process may be used with different polymers at a wide range of temperature. Due to low excipient concentration, this granulation method is especially suitable for high-dose tablets.

  20. CLINICAL INVESTIGATIONS ON THE AYURVEDIC MANAGEMENT OF ALLERGIC RHINITIS (VATAJA PRATISHYAYA BY PRATIMARSHA NASYAAS NASAL DRUG DELIVERY SYSTEM.

    Directory of Open Access Journals (Sweden)

    Shiva Kumar

    2014-12-01

    Full Text Available Allergic Rhinitis (AR is an immunoglobulin (Ig E mediated inflammatory disease caused by the inflammation of airway mucosa with hypersensitivity resulting from seasonal or perennial responses to specific allergens. Prevalence of AR is increasing and has risen considerably in the past few decades with self reported prevalence up to 41%. According to Ayurvedic texts indication of Anutaila (classical Ayurvedic oil preparation used in the form of Pratimarsha Nasya a traditional nasal drug delivery system has been used for a long period has shown beneficial effects on diseases of head and neck. A pretest and post test design of single group consisting of 37 patientsdiagnosed as allergic rhinitis were administered Pratimarsha Nasya (PNwith Anutaila daily for a period of 60 days. Effect ofPratimarsha Nasya with Anutaila on the chief complaints and totals nasal symptom score showed ameliorative improvement with statistical significance. Laboratory immunological parameters which included Total Leucocyte Count, Absolute Eosinophil Count, Neutrophils and Lymphocytes showed improvement with high statistical significance (< 0.001. At the end after 60 days of medication the patients showed marked relief in symptoms which can open a new direction in Ayurveda inspired novel targeted drug delivery systems.

  1. Drug allergy

    Directory of Open Access Journals (Sweden)

    Warrington Richard

    2011-11-01

    Full Text Available Abstract Drug allergy encompasses a spectrum of immunologically-mediated hypersensitivity reactions with varying mechanisms and clinical presentations. This type of adverse drug reaction (ADR not only affects patient quality of life, but may also lead to delayed treatment, unnecessary investigations, and even mortality. Given the myriad of symptoms associated with the condition, diagnosis is often challenging. Therefore, referral to an allergist experienced in the identification, diagnosis and management of drug allergy is recommended if a drug-induced allergic reaction is suspected. Diagnosis relies on a careful history and physical examination. In some instances, skin testing, graded challenges and induction of drug tolerance procedures may be required. The most effective strategy for the management of drug allergy is avoidance or discontinuation of the offending drug. When available, alternative medications with unrelated chemical structures should be substituted. Cross-reactivity among drugs should be taken into consideration when choosing alternative agents. Additional therapy for drug hypersensitivity reactions is largely supportive and may include topical corticosteroids, oral antihistamines and, in severe cases, systemic corticosteroids. In the event of anaphylaxis, the treatment of choice is injectable epinephrine. If a particular drug to which the patient is allergic is indicated and there is no suitable alternative, induction of drug tolerance procedures may be considered to induce temporary tolerance to the drug. This article provides a backgrounder on drug allergy and strategies for the diagnosis and management of some of the most common drug-induced allergic reactions, such allergies to penicillin, sulfonamides, cephalosporins, radiocontrast media, local anesthetics, general anesthetics, acetylsalicylic acid (ASA and non-steroidal anti-inflammatory drugs.

  2. An investigation into possible xenobiotic-endobiotic inter-relationships involving the amino acid analogue drug, S-carboxymethyl-L-cysteine and plasma amino acids in humans.

    Science.gov (United States)

    Steventon, Glyn B; Mitchell, Stephen C; Angulo, Santigo; Barbas, Coral

    2012-05-01

    The amino acid derivative, S-carboxymethyl-L-cysteine, is an anti-oxidant agent extensively employed as adjunctive therapy in the treatment of human pulmonary conditions. A major biotransformation route of this drug, which displays considerable variation in capacity in man, involves the oxidation of the sulfide moiety to the inactive S-oxide metabolite. Previous observations have indicated that fasted plasma L-cysteine concentrations and fasted plasma L-cysteine/free inorganic sulfate ratios were correlated with the degree of sulfoxidation of this drug and that these particular parameters may be used as endobiotic biomarkers for this xenobiotic metabolism. It has been proposed also that the enzyme, cysteine dioxygenase, was responsible for the drug sulfoxidation. Further in this theme, the degree of S-oxidation of S-carboxymethyl-L-cysteine in 100 human volunteers was investigated with respect to it potential correlation with fasted plasma amino acid concentrations. Extensive statistical analyses showed no significant associations or relationships between the degree of drug S-oxidation and fasted plasma amino acid concentrations, especially with respect to the sulfur-containing compounds, methionine, L-cysteine, L-cysteine sulfinic acid, taurine and free inorganic sulfate, also the derived ratios of L-cysteine/L-cysteine sulfinic acid and L-cysteine/free inorganic sulfate. It was concluded that plasma amino acid levels or derived ratios cannot be employed to predict the degree of S-oxidation of S-carboxymethyl-L-cysteine (or vice versa) and that it is doubtful if the enzyme, cysteine dioxygenase, has any involvement in the metabolism of this drug.

  3. Microdialysis sampling for investigations of bioavailability and bioequivalence of topically administered drugs: current state and future perspectives

    DEFF Research Database (Denmark)

    Holmgaard, R; Nielsen, J B; Benfeldt, E

    2010-01-01

    Microdialysis (MD) in the skin is a unique technique for in vivo sampling of topically as well as systemically administered drugs at the site of action, e.g. sampling the unbound tissue concentrations in the dermis and subcutaneous tissue. MD as a research method has undergone significant...... by skin disease or barrier perturbation. A comparison between MD and other tissue sampling techniques reveals the advantages and limitations of the method. Subsequently, an in-depth discussion of the application of MD for the evaluation of bioavailability and bioequivalence of topical formulations...... development, improvement and validation during the last decade and has proved to be a versatile, safe and valuable tool for pharmacokinetic and pharmacodynamic studies. This review gives an overview of the current state and future perspectives of dermal MD sampling. Methodological issues such as choice...

  4. Clinical Trial Electronic Portals for Expedited Safety Reporting: Recommendations from the Clinical Trials Transformation Initiative Investigational New Drug Safety Advancement Project.

    Science.gov (United States)

    Perez, Raymond P; Finnigan, Shanda; Patel, Krupa; Whitney, Shanell; Forrest, Annemarie

    2016-12-15

    Use of electronic clinical trial portals has increased in recent years to assist with sponsor-investigator communication, safety reporting, and clinical trial management. Electronic portals can help reduce time and costs associated with processing paperwork and add security measures; however, there is a lack of information on clinical trial investigative staff's perceived challenges and benefits of using portals. The Clinical Trials Transformation Initiative (CTTI) sought to (1) identify challenges to investigator receipt and management of investigational new drug (IND) safety reports at oncologic investigative sites and coordinating centers and (2) facilitate adoption of best practices for communicating and managing IND safety reports using electronic portals. CTTI, a public-private partnership to improve the conduct of clinical trials, distributed surveys and conducted interviews in an opinion-gathering effort to record investigator and research staff views on electronic portals in the context of the new safety reporting requirements described in the US Food and Drug Administration's final rule (Code of Federal Regulations Title 21 Section 312). The project focused on receipt, management, and review of safety reports as opposed to the reporting of adverse events. The top challenge investigators and staff identified in using individual sponsor portals was remembering several complex individual passwords to access each site. Also, certain tasks are time-consuming (eg, downloading reports) due to slow sites or difficulties associated with particular operating systems or software. To improve user experiences, respondents suggested that portals function independently of browsers and operating systems, have intuitive interfaces with easy navigation, and incorporate additional features that would allow users to filter, search, and batch safety reports. Results indicate that an ideal system for sharing expedited IND safety information is through a central portal used by

  5. Pharmaceutical characterization of novel tenofovir liposomal formulations for enhanced oral drug delivery: in vitro pharmaceutics and Caco-2 permeability investigations

    Directory of Open Access Journals (Sweden)

    Spinks CB

    2017-02-01

    Full Text Available Crystal B Spinks,1 Ahmed S Zidan,2,3 Mansoor A Khan,4 Muhammad J Habib,1 Patrick J Faustino2 1Department of Pharmaceutical Sciences, School of Pharmacy, Howard University, Washington, DC, 2Division of Product Quality Research, Office of Pharmaceutical Quality, Food and Drug Administration, Silver Spring, MD, USA; 3Faculty of Pharmacy, Zagazig University, Zagazig, Egypt; 4Irma Lerma Rangel College of Pharmacy, Texas A&M Health Science Center, College Station, TX, USA Abstract: Tenofovir, currently marketed as the prodrug tenofovir disoproxil fumarate, is used clinically to treat patients with HIV/AIDS. The oral bioavailability of tenofovir is relatively low, limiting its clinical effectiveness. Encapsulation of tenofovir within modified long-circulating liposomes would deliver this hydrophilic anti-HIV drug to the reticuloendothelial system for better therapeutic efficacy. The objectives of the current study were to prepare and pharmaceutically characterize model liposomal tenofovir formulations in an attempt to improve their bioavailability. The entrapment process was performed using film hydration method, and the formulations were characterized in terms of encapsulation efficiency and Caco-2 permeability. An efficient reverse-phase high-performance liquid chromatography method was developed and validated for tenofovir quantitation in both in vitro liposomal formulations and Caco-2 permeability samples. Separation was achieved isocratically on a Waters Symmetry C8 column using 10 mM Na2PO4/acetonitrile pH 7.4 (95:5 v/v. The flow rate was 1 mL/min with a 12 min elution time. Injection volume was 10 µL with ultraviolet detection at 270 nm. The method was validated according to United States Pharmacopeial Convention category I requirements. The obtained result showed that tenofovir encapsulation within the prepared liposomes was dependent on the employed amount of the positive charge-imparting agent. The obtained results indicated that

  6. Nanoparticle Fullerene (C60) demonstrated stable binding with antibacterial potential towards probable targets of drug resistant Salmonella typhi - a computational perspective and in vitro investigation.

    Science.gov (United States)

    Skariyachan, Sinosh; Parveen, Asma; Garka, Shruti

    2016-11-23

    Salmonella typhi, a Gram negative bacterium, has become multidrug resistant (MDR) to wide classes of antibacterials which necessitate an alarming precaution. This study focuses on the binding potential and therapeutic insight of Nano-Fullerene C60 towards virulent targets of Salmonella typhi by computational prediction and preliminary in vitro assays. The clinical isolates of Salmonella typhi were collected and antibiotic susceptibility profiles were assessed. The drug targets of pathogen were selected by rigorous literature survey and gene network analysis by various metabolic network resources. Based on this study, 20 targets were screened and the 3D structures of few drug targets were retrieved from PDB and others were computationally predicted. The structures of nanoleads such as Fullerene C60, ZnO and CuO were retrieved from drug databases. The binding potential of these nanoleads towards all selected targets were predicted by molecular docking. The best docked conformations were screened and concept was investigated by preliminary bioassays. This study revealed that most of the isolates of Salmonella typhi were found to be MDR (p Salmonella typhi.

  7. 海布胶囊原料药稳定性实验研究%Stability Investigation of Bulk Drug in Haibu Capsule

    Institute of Scientific and Technical Information of China (English)

    王喜斌; 左红香; 王曼力; 黄耀林; 刘庆波; 孙亚楠

    2015-01-01

    目的:考察海布胶囊原料药的稳定性.方法按药物稳定性实验指导原则进行影响因素实验、加速实验和长期实验.结果海布胶囊原料药在实验前后的外观、鉴别、吸湿性、微生物限度检查等均符合规定,实验前后比较差异无统计学意义(P<0.05).结论海布胶囊于室温条件下保存质量稳定,有效期可达2 a.%Objective The stability of bulk drug in Haibu capsule was investigated. Method Stress test, accelerated test and long-term test were carried out according to the principles referring to the drug stability. Results The quality of the principal agent in Haibu capsule, including appearance, identification, moisture absorption and microorganism limitation, accorded with regulation after the stability tests, and no statistical difference was detected ( P<0 . 05 ) . Conclusion The bulk drug can maintain its stability and feasibility for 2 years at room temperature.

  8. Different HPMC viscosity grades as coating agents for an oral time and/or site-controlled delivery system: an investigation into the mechanisms governing drug release.

    Science.gov (United States)

    Zema, L; Maroni, A; Foppoli, A; Palugan, L; Sangalli, M E; Gazzaniga, A

    2007-06-01

    When used as release-controlling coating agents for tableted core-based pulsatile delivery systems, three different hydroxypropyl methylcellulose (HPMC) grades, Methocel E5, E50, and K4M, provided lag phases of varying duration (Methocel K4M > E50 > E5) and a prompt and quantitative model drug release. Dissolution/mechanical erosion, permeability increase and disruption of the hydrated polymeric layer were assumed to participate in the definition of the overall release pattern. Based on these premises, we investigated what process(es) might prevail in the release-controlling mechanism for each HPMC grade. The polymers were evaluated for dissolution and swelling, while the finished systems were concomitantly evaluated for drug release and polymer dissolution. The obtained results indicated likely similarities between Methocel E5 and E50 performances, which we hypothesized to be mainly dissolution/erosion-controlled, and a clearly different behavior for Methocel K4M. This polymer indeed proved to yield higher viscosity and slower dissolving gel layer, which was able to withstand extensive dissolution/erosion for periods that exceeded the observed lag phases. The particular characteristics of swollen Methocel K4M were shown to be associated with possible drug diffusion phenomena, which might impair the prompt and quantitative release phase that is typical of pulsatile delivery.

  9. Experimental and theoretical investigations of Lantana camara oil diffusion from polyacrylonitrile membrane for pulsatile drug delivery system

    Energy Technology Data Exchange (ETDEWEB)

    Verma, Vivek [Department of Chemistry, Indian Institute of Science Education and Research (IISER), Pune 411008 (India); Balasubramanian, K., E-mail: meetkbs@gmail.com [Department of Materials Engineering, Defence Institute of Advance Technology (DIAT), Ministry of Defence, Girinagar, Pune 411025 (India)

    2014-08-01

    Porous composite membrane of polyacrylonitrile (PAN) and Lantana camara essential oil was synthesized by solvent casting method. Stability of oil in PAN solution was measured by XiGo nano tool indicating constant relaxation time of 1487 time/s. Pore size of few microns confirmed by electron microscopy was supported by atomic force microscopy indicating roughness factor of 0.9 nm. Contact angle of 2° inveterates superhydrophilicity of the composite membrane. Membrane showed excellent antibacterial activity against both Gram-positive Bacillus subtilis and Gram-negative Escherichia coli with a 7–10 mm zone of inhibition. In vitro release of Lantana oil from the composite membrane was carried out in isotonic phosphate buffer solution (pH = 7.4). Lantana oil was released for 9 h, lag time of 3 h with constant 33% release confirmed PAN membranes as potential system for pulsatile drug delivery applications. Diffusion of E-caryophyllene (antibacterial component of oil) which was studied through molecular simulation using Material Studio software ensued diffusion coefficient value of 1.11 ∗ 10{sup −9} m{sup 2}/s. Biocompatibility of the composite membrane was assessed by mouse embryonic fibroblast cell line (NIH 3T3) through MTT assay indicating more than 91% viable cell even at 200 μg/mL concentration. Such membranes can be efficiently used in biomedical applications as antibacterial and antifungal agent. - Highlights: • Pulsatile release • Lantana oil–PAN composite membrane as antibacterial material • Enhanced bactericidal activity of the membrane.

  10. Extracting physical chemistry from mechanics: a new approach to investigate DNA interactions with drugs and proteins in single molecule experiments.

    Science.gov (United States)

    Rocha, M S

    2015-09-01

    In this review we focus on the idea of establishing connections between the mechanical properties of DNA-ligand complexes and the physical chemistry of DNA-ligand interactions. This type of connection is interesting because it opens the possibility of performing a robust characterization of such interactions by using only one experimental technique: single molecule stretching. Furthermore, it also opens new possibilities in comparing results obtained by very different approaches, in particular when comparing single molecule techniques to ensemble-averaging techniques. We start the manuscript reviewing important concepts of DNA mechanics, from the basic mechanical properties to the Worm-Like Chain model. Next we review the basic concepts of the physical chemistry of DNA-ligand interactions, revisiting the most important models used to analyze the binding data and discussing their binding isotherms. Then, we discuss the basic features of the single molecule techniques most used to stretch DNA-ligand complexes and to obtain "force × extension" data, from which the mechanical properties of the complexes can be determined. We also discuss the characteristics of the main types of interactions that can occur between DNA and ligands, from covalent binding to simple electrostatic driven interactions. Finally, we present a historical survey of the attempts to connect mechanics to physical chemistry for DNA-ligand systems, emphasizing a recently developed fitting approach useful to connect the persistence length of DNA-ligand complexes to the physicochemical properties of the interaction. Such an approach in principle can be used for any type of ligand, from drugs to proteins, even if multiple binding modes are present.

  11. Social-structural contexts of needle and syringe sharing behaviours of HIV-positive injecting drug users in Manipur, India: a mixed methods investigation

    Directory of Open Access Journals (Sweden)

    Shunmugam Murali

    2011-05-01

    Full Text Available Abstract Background Few investigations have assessed risk behaviours and social-structural contexts of risk among injecting drug users (IDUs in Northeast India, where injecting drug use is the major route of HIV transmission. Investigations of risk environments are needed to inform development of effective risk reduction interventions. Methods This mixed methods study of HIV-positive IDUs in Manipur included a structured survey (n = 75, two focus groups (n = 17, seven in-depth interviews, and two key informant interviews. Results One-third of survey participants reported having shared a needle/syringe in the past 30 days; among these, all the men and about one-third of the women did so with persons of unknown HIV serostatus. A variety of social-structural contextual factors influenced individual risk behaviours: barriers to carrying sterile needles/syringes due to fear of harassment by police and "anti-drug" organizations; lack of sterile needles/syringes in drug dealers' locales; limited access to pharmacy-sold needles/syringes; inadequate coverage by needle and syringe programmes (NSPs; non-availability of sterile needles/syringes in prisons; and withdrawal symptoms superseding concern for health. Some HIV-positive IDUs who shared needles/syringes reported adopting risk reduction strategies: being the 'last receiver' of needles/syringes and not a 'giver;' sharing only with other IDUs they knew to be HIV-positive; and, when a 'giver,' asking other IDUs to wash used needles/syringes with bleach before using. Conclusions Effective HIV prevention and care programmes for IDUs in Northeast India may hinge on several enabling contexts: supportive government policy on harm reduction programmes, including in prisons; an end to harassment by the police, army, and anti-drug groups, with education of these entities regarding harm reduction, creation of partnerships with the public health sector, and accountability to government policies that protect IDUs

  12. A theoretical and empirical investigation into the willingness-to-pay function for new innovative drugs by Germany's health technology assessment agency (IQWiG).

    Science.gov (United States)

    Gandjour, Afschin

    2013-11-01

    Under the recently enacted pharmaceutical price and reimbursement regulation in Germany, new drugs are subject to a rapid assessment to determine whether there is sufficient evidence of added clinical benefits compared with the existing standard of treatment. If such added benefits are confirmed, manufacturers and representatives of the Statutory Health Insurance (SHI) are expected to negotiate an appropriate reimbursement price. If parties fail to reach an agreement, a final decision on the reimbursement price will be made by an arbitration body. If one of the parties involved wishes so, then the Institute for Quality and Efficiency in Health Care (Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen, IQWiG) will be commissioned with a formal evaluation of costs and benefits of the product in question. IQWiG will make a recommendation for a reimbursement price based on the 'efficiency frontier' in a therapeutic area. The purpose of the assessments is to provide support for decision-making bodies that act on behalf of the SHI insurants. To determine the willingness to pay for new drugs, IQWiG uses the following decision rule: the incremental cost-effectiveness ratio of a new drug compared with the next effective intervention should not be higher than that of the next effective intervention compared with its comparator. The purpose of this paper was to investigate the theoretical and empirical relationship between the willingness to pay for drugs and their health benefits. The analysis shows that across disease areas IQWiG has a curvilinear relationship between willingness to pay and health benefits. Future research may address the validity of the willingness-to-pay function from the viewpoint of the individual SHI insurants.

  13. Comparative in vitro and in vivo pharmacological investigation of platinum(IV) complexes as novel anticancer drug candidates for oral application.

    Science.gov (United States)

    Theiner, Sarah; Varbanov, Hristo P; Galanski, Markus; Egger, Alexander E; Berger, Walter; Heffeter, Petra; Keppler, Bernhard K

    2015-01-01

    Platinum(IV) complexes are promising candidates as prodrugs for oral application in anticancer chemotherapy. However, only a few Pt(IV) compounds entered (pre)clinical trials, e.g. satraplatin, while most of the others were only tested in vitro. Aim of the study was investigation of the in vivo pharmacological behavior as well as the anticancer activity of two novel platinum(IV) complexes vs. satraplatin. The drugs were selected due to significantly different in vitro cytotoxicity while sharing some physicochemical properties (e.g. lipophilicity). Initial experiments indicated that the highly in vitro cytotoxic compound 1 ((OC-6-33)-dichloridobis((4-ethoxy)-4-oxobutanoato)-bis(ethylamine)platinum(IV)) was also characterized by high drug absorption and tissue platinum levels after oral application. Interestingly, analysis of serum samples using SEC-ICP-MS revealed that the administered drugs have completely been metabolized and/or bound to proteins in serum within 2 h after treatment. With regard to the activity in vivo, the outcomes were rather unexpected: although potent anticancer effect of 1 was observed in cell culture, the effects in vivo were rather minor. Nevertheless, 1 was superior to 2 ((OC-6-33)-diammine(cyclobutane-1,1-dicarboxylato)-bis((4-cyclopentylamino)-4-oxobutanoato)platinum(IV)) after i.p. administration, which was, at least to some extent, in accordance to the cell culture experiments. After oral gavage, both compounds exhibited comparable activity. This is remarkable considering the distinctly lower activity of 2 in cell culture as well as the low platinum levels detected both in serum and tissues after oral application. Consequently, our data indicate that the prediction of in vivo anticancer activity by cell culture experiments is not trivial, especially for orally applied drugs.

  14. [Investigation of community support measures for patients with comorbid substance use disorder and psychotic disorder: nationwide survey of drug addiction rehabilitation centers].

    Science.gov (United States)

    Ikeda, Tomohiro; Koike, Junko; Kouda, Minoru; Inamoto, Atsuko; Morota, Nobuaki

    2014-12-01

    In psychiatric care practice, patients are often seen who have difficulty with their social lives due to protracted psychiatric symptoms despite years without drug abuse. The difficulty of dealing with such cases and the lack of preparedness of the legal system leave circumstantial care as the only option. Western.countries have recently begun using the name 'concurrent disorder' as a diagnosis for patients deemed unable to recover solely through such treatment for drug addiction, signifying the presence of both a substance use disorder (SUD) and a mental health disorder. Various assessment and intervention methods are being investigated, and many studies have been reported. Based on the hypothesis that Drug Addiction Rehabilitation Center (DARC) are partly involved in supporting those with psychotic concurrent disorders (PSCD) in Japan, we conducted a survey to clarify the actual support for PSCD patients at DARC and the challenges they face. Surveys were administered to DARC-related institutions all over Japan (44 governing organizations and 66 institutions). Complete responses from 86 full-time employees and 445 DARC users were analyzed. DARC users were divided into two groups: psychiatric concurrent disorders (PSCD group, n = 178) and those without such symptoms (SUD group, n = 267), with the PSCD group accounting for 40% of the DARC users surveyed. Compared to the SUD group, the PSCD group was significantly less satisfied with their lifestyle and interpersonal relations at the DARC and a significantly higher proportion of the PSCD group requested assistance in communicating with others. When employees were presented with a hypothetical PSCD case and asked what was needed to deal with it, some responses were, "an institution that can treat both drug addiction and other mental health disorders," "a psychiatric care institution that provides 24-hour care," and "sufficient manpower and training." In the future, a treatment system must be established based on

  15. Clinical investigation of diabetes drugs in our hospital in 2013%2013年我院糖尿病药物临床应用调查

    Institute of Scientific and Technical Information of China (English)

    王晓珉; 张武标; 邵丽丽

    2015-01-01

    目的:了解医院口服糖尿病药物的应用情况,为临床合理用药提供参考。方法采用限定日剂量分析方法,对医院2013年口服抗糖尿病药物的销售金额、用药频度等指标进行统计分析。结果2013年住院患者使用糖尿病药物年度金额前三名分别是拜糖平、格华止、达美康;DDDs 年度排名前三位的分别是糖适平、格华止、格列美脲片。胰岛素中诺和灵30R 笔芯和优泌灵30/70笔芯用量占全部胰岛素用量的40%以上。结论医院糖尿病药物使用基本合理。%Objective To investigate the application of oral diabetes drugs in our hospital. provide reference for clini-cal rational drug use. Methods By using the defined daily dose analysis method,sales amount,DDDs and other indicators of oral antihypertensive drugs in our hospital in 2013 were counted and analyzed. Results In 2013,the top three annual amount is Glucobay、metformin、Diamicron;annual DDDs the top three is Gliquidone、metformin、Glimepiride. In using of Insulin,Nov-olin 30 R cartridge and Humulin 30 / 70 cartridge consumption accounted for more than 40% of the total dosage of insulin,clin-ical response is better than other Insulin. Conclusion The use of Diabetes drugs in our hospital is basically rational.

  16. Computational studies of formation silicon nanotubes-propylthiouracil hybrids to investigate its role in confining propylthiouracil drug

    Directory of Open Access Journals (Sweden)

    A. Shameli

    2016-03-01

    Full Text Available In order to search for the interaction between Propythiouracil(ptu and infinitely long armchair single-walled silicon nanotubes (SiNTs is investigated using density functional theory (DFT. The structures of individual counterparts and hybrids have been optimized and the molecular properties have been evaluated. The Nuclear magnetic resonance spectroscopy (NMR are witness to the substantial changes in the electronic properties of the SiNTs systems following the attachment of the ptu with the tube surface.

  17. Searching for Truth: Internet Search Patterns as a Method of Investigating Online Responses to a Russian Illicit Drug Policy Debate

    OpenAIRE

    Zheluk, Andrey; Gillespie, James A.; Quinn, Casey

    2012-01-01

    Background This is a methodological study investigating the online responses to a national debate over an important health and social problem in Russia. Russia is the largest Internet market in Europe, exceeding Germany in the absolute number of users. However, Russia is unusual in that the main search provider is not Google, but Yandex. Objective This study had two main objectives. First, to validate Yandex search patterns against those provided by Google, and second, to test this method's a...

  18. Pharmaceutical characterization of novel tenofovir liposomal formulations for enhanced oral drug delivery: in vitro pharmaceutics and Caco-2 permeability investigations.

    Science.gov (United States)

    Spinks, Crystal B; Zidan, Ahmed S; Khan, Mansoor A; Habib, Muhammad J; Faustino, Patrick J

    2017-01-01

    Tenofovir, currently marketed as the prodrug tenofovir disoproxil fumarate, is used clinically to treat patients with HIV/AIDS. The oral bioavailability of tenofovir is relatively low, limiting its clinical effectiveness. Encapsulation of tenofovir within modified long-circulating liposomes would deliver this hydrophilic anti-HIV drug to the reticuloendothelial system for better therapeutic efficacy. The objectives of the current study were to prepare and pharmaceutically characterize model liposomal tenofovir formulations in an attempt to improve their bioavailability. The entrapment process was performed using film hydration method, and the formulations were characterized in terms of encapsulation efficiency and Caco-2 permeability. An efficient reverse-phase high-performance liquid chromatography method was developed and validated for tenofovir quantitation in both in vitro liposomal formulations and Caco-2 permeability samples. Separation was achieved isocratically on a Waters Symmetry C8 column using 10 mM Na2PO4/acetonitrile pH 7.4 (95:5 v/v). The flow rate was 1 mL/min with a 12 min elution time. Injection volume was 10 µL with ultraviolet detection at 270 nm. The method was validated according to United States Pharmacopeial Convention category I requirements. The obtained result showed that tenofovir encapsulation within the prepared liposomes was dependent on the employed amount of the positive charge-imparting agent. The obtained results indicated that calibration curves were linear with r(2) > 0.9995 over the analytical range of 1-10 µg/mL. Inter- and intraday accuracy and precision values ranged from 95% to 101% and 0.3% to 2.6%, respectively. The method was determined to be specific and robust. Regarding the potential of the prepared vectors to potentiate tenofovir permeability through the Caco-2 model, a 10-fold increase in tenofovir apparent permeability was observed compared to its oral solution. In conclusion, this novel and validated method was

  19. Permeapad™ for investigation of passive drug permeability: The effect of surfactants, co-solvents and simulated intestinal fluids (FaSSIF and FeSSIF).

    Science.gov (United States)

    Bibi, Hanady Ajine; di Cagno, Massimiliano; Holm, Rene; Bauer-Brandl, Annette

    2015-09-30

    The aim of the present work was to investigate the potential of the new and innovative artificial barrier, Permeapad™, when exposed to surfactants and co-solvents, often employed for poorly water soluble compounds. The barrier was in addition also exposed to fasted and fed state simulated intestinal fluids versions 1 and 2 (FaSSIF and FeSSIF), all of which the Permeapad™ barrier was compatible with based upon relative comparison of the permeability of the hydrophilic marker calcein in phosphate buffer. The new barrier therefore holds a huge potential due to its functional stability and robustness. It can be used as a standard tool to investigate permeability of drugs in the presence of different surfactants and co-solvents, from DMSO stock solutions at even high concentrations and for the evaluation of permeability in the presence of biomimetic media (BMM). Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Using the Theory of Planned Behavior to investigate condom use behaviors among female injecting drug users who are also sex workers in China.

    Science.gov (United States)

    Gu, Jing; Lau, Joseph T F; Chen, Xi; Liu, Chuliang; Liu, Jun; Chen, Hongyao; Wang, Renfan; Lei, Zhangquan; Li, Zhenglin

    2009-08-01

    Female injecting drug users who are sex workers (IDUFSWs) is a strategic "bridge population" for HIV transmission. Goals of the study were to investigate condom use behaviors during commercial sex among IDUFSWs using the Theory of Planned Behavior (TPB), and to investigate moderating effects that modify the strength of associations between the TPB-related variables and inconsistent condom use during commercial sex. A total of 281 non-institutionalized IDUFSWs were recruited using snowball sampling method. Anonymous face-to-face interviews were administered by trained doctors. The results showed that the prevalence of inconsistent condom use during commercial sex in the last six months was 64%. After adjusting for some significant background variables (e.g. main venue of sex work), all associations between the five TPB-related variables and the studied condom use variable were statistically significant (Odds Ratio (OR) = 0.43-0.68, pBehavioral Control Scale and the Behavioral Intention Scale were selected by the second step (OR = 0.67 - 0.72, pBehavioral Intention Scale) and duration of sex work and duration of drug use were also reported. The results highlighted the potential of using the TPB to better understand condom use behaviors in IDUFSWs in China. Theory-based research and intervention work should be developed in China in the future.

  1. Analysis of warning letters issued by the US Food and Drug Administration to clinical investigators, institutional review boards and sponsors: a retrospective study.

    Science.gov (United States)

    Shetty, Yashashri C; Saiyed, Aafreen A

    2015-05-01

    The US Food and Drug Administration (FDA) issues warning letters to all research stakeholders if unacceptable deficiencies are found during site visits. Warning letters issued by the FDA between January 2011 and December 2012 to clinical investigators and institutional review boards (IRBs) were reviewed for various violation themes and compared to similar studies in the past. Warning letters issued to sponsors between January 2005 and December 2012 were analysed for the first time for a specific set of violations using descriptive statistics. Failure to protect subject safety and to report adverse events to IRBs was found to be significant compared to prior studies for clinical investigators, while failure to follow standard operating procedures and maintain documentation was noted as significant in warning letters to IRBs. Failure to maintain minutes of meeting and to follow written procedures for continuing review were new substantial violations in warning letters issued to IRBs. Forty-six warning letters were issued to sponsors, the most common violations being failure to follow a monitoring schedule (58.69%), failure to obtain investigator agreement (34.78%), failure to secure investigators' compliance (30.43%), and failure to maintain data records and ship documents to investigators (30.43%). Appropriate methods for handling clinical trial procedural violations should be developed and implemented worldwide.

  2. Automated analysis of behavior: a computer-controlled system for drug screening and the investigation of learning.

    Science.gov (United States)

    Hicks, Caitlin; Sorocco, Debra; Levin, Michael

    2006-08-01

    Efforts to understand cognition will be greatly facilitated by computerized systems that enable the automated analysis of animal behavior. A number of controversies in the invertebrate learning field have resulted from difficulties inherent in manual experiments. Driven by the necessity to overcome these problems during investigation of neural function in planarian flatworms and frog larvae, we designed and developed a prototype for an inexpensive, flexible system that enables automated control and analysis of behavior and learning. Applicable to a variety of small animals such as flatworms and zebrafish, this system allows automated analysis of innate behavior, as well as of learning and memory in a plethora of conditioning paradigms. We present here the schematics of a basic prototype, which overcomes experimenter effects and operator tedium, enabling a large number of animals to be analyzed with transparent on-line access to primary data. A scaled-up version of this technology represents an efficient methodology to screen pharmacological and genetic libraries for novel neuroactive reagents of basic and biomedical relevance.

  3. Sterically stabilized polymeric nanoparticles with a combinatorial approach for multi drug resistant cancer: in vitro and in vivo investigations.

    Science.gov (United States)

    Zafar, Sobiya; Negi, Lalit Mohan; Verma, Anita Kamra; Kumar, Vijay; Tyagi, Aakriti; Singh, Pratibha; Iqbal, Zeenat; Talegaonkar, Sushama

    2014-12-30

    The present work describes the preparation of sterically stabilize polymeric nanoparticles of mitoxantrone dihydrochloride (MTO) along with an efflux transporter (Pgp/BCRP) inhibitor that enhance the circulation time of nanoparticles and simultaneously surmount the problem of multidrug resistance (MDR). Mitoxantrone dihydrochloride being hydrophilic in nature had very low entrapment efficiency (%E.E.), thus in order to further enhance the lipophilicity and the %E.E., it was complexed with sodium deoxycholate (SDC) and this MTO-SDC-complex was used to formulate nanoparticles with/without Pgp/BCRP inhibitor by nanoprecipitation technique and was characterized for various in vitro and in vivo attributes. In vitro cell line studies were conducted on MCF7, A2780(p) and A2780(adr) cells. Furthermore, the targeting potential of hyaluronic acid (HA) coated nanoparticles for CD44 receptors was investigated using the MCF7 cell line. A reduction in the IC50 value observed with the inhibitor loaded nanoparticles in different cell lines indicated the BCRP/Pgp inhibiting ability of the formulated nanoparticles. The reduced macrophage uptake and the increased residence time in blood demonstrated the long circulating behaviour of the nanoparticles. The enhanced cellular uptake of HA coated nanoparticles in MCF7 cells revealed their targeting potential. The HA coated nanoparticles along with efflux transporter inhibitor exhibits a great potential for targeted chemotherapy in CD44 overexpressing MDR breast cancer.

  4. Investigation of a secondary syringe exchange program for homeless young adult injection drug users in San Francisco, California, U.S.A.

    Science.gov (United States)

    Sears, C; Guydish, J R; Weltzien, E K; Lum, P J

    2001-06-01

    This study investigated an HIV prevention program for homeless young adult injection drug users (IDUs) that combined a secondary syringe exchange program (SEP) with community-level activities. Homeless young IDUs were recruited from street-based settings in San Francisco, and a structured questionnaire was administered. The secondary SEP operated in a circumscribed geographic area, and for analytic purposes respondents were assigned to the intervention site group if they primarily spent time in this area (n = 67), or the comparison site group if they primarily spent time elsewhere (n = 55). Almost all (96%) intervention site youth had used the secondary SEP in the past 30 days and were significantly more likely to regularly use SEP. In bivariate analysis, comparison site IDUs were more likely to share syringes, reuse syringes, share the cotton used to filter drugs, and use condoms with casual sex partners only inconsistently. In multivariate analysis, comparison site remained positively associated with sharing syringes (adjusted odds ratio [AOR], 3.748; 95% confidence interval [CI], 1.406-9.988), reusing syringes (AOR, 2.769; 95% CI,1.120-6.847), and inconsistent condom use with casual sex partners (AOR, 4.825; 95% CI, 1.392- 16.721). This suggests that the intervention was effective in delivering SEP services to homeless young adult IDUs, and that IDUs who frequented the intervention site had a lower HIV risk than comparison group IDUs.

  5. Ginger components as new leads for the design and development of novel multi-targeted anti-Alzheimer’s drugs: a computational investigation

    Directory of Open Access Journals (Sweden)

    Azam F

    2014-10-01

    Full Text Available Faizul Azam,1,2 Abdualrahman M Amer,1 Abdullah R Abulifa,1 Mustafa M Elzwawi1 1Faculty of Pharmacy, Misurata University, Misurata, Libya; 2Department of Pharmaceutical Chemistry, Nims Institute of Pharmacy, Nims University, Jaipur, Rajasthan, India Abstract: Ginger (Zingiber officinale, despite being a common dietary adjunct that contributes to the taste and flavor of foods, is well known to contain a number of potentially bioactive phytochemicals having valuable medicinal properties. Although recent studies have emphasized their benefits in Alzheimer’s disease, limited information is available on the possible mechanism by which it renders anti-Alzheimer activity. Therefore, the present study seeks to employ molecular docking studies to investigate the binding interactions between active ginger components and various anti-Alzheimer drug targets. Lamarckian genetic algorithm methodology was employed for docking of 12 ligands with 13 different target proteins using AutoDock 4.2 program. Docking protocol was validated by re-docking of all native co-crystallized ligands into their original binding cavities exhibiting a strong correlation coefficient value (r2=0.931 between experimentally reported and docking predicted activities. This value suggests that the approach could be a promising computational tool to aid optimization of lead compounds obtained from ginger. Analysis of binding energy, predicted inhibition constant, and hydrophobic/hydrophilic interactions of ligands with target receptors revealed acetylcholinesterase as most promising, while c-Jun N-terminal kinase was recognized as the least favorable anti-Alzheimer’s drug target. Common structural requirements include hydrogen bond donor/acceptor area, hydrophobic domain, carbon spacer, and distal hydrophobic domain flanked by hydrogen bond donor/acceptor moieties. In addition, drug-likeness score and molecular properties responsible for a good pharmacokinetic profile were calculated

  6. 超声药物释放空化动力学行为研究%Investigation of Microbubble Dynamics in Drug Release by Ultrasound Cavitation

    Institute of Scientific and Technical Information of China (English)

    梁士利; 韩冬; 徐美玲; 崔霜; 张玲

    2012-01-01

    以直径1μm的脂质体为空化研究对象,从修正的Rayleigh空化方程入手,研究机械系数(MI)对300 kHz和1 MHz超声作用时空化效应的影响.脂质体的药物释放以超声作用前后脂质体中钙黄绿素的荧光强度为量度.模拟结果表明:在微泡振荡过程中,由超声波驱动产生的负向最大泡壁运动速度促使微泡半径从最大快速减小接近于零,微泡积聚到最大能量.对于300 kHz和1 MHz的激励超声,存在一个拐点(MI)值,当MI小于接近0.4时,1 MHz微泡半径变化幅度强于300 kHz;当MI>0.4时,300 kHz微泡半径变化幅度强于1MHz.这一结果预示在此范围内,300kHz的药物释放效果好于1MHz.本研究为超声空化效应研究及超声药物释放应用提供了理论依据.%The cavitation of a liposome microbubble dynamics in drug release was studied. The main objective of this work was to investigate the role by the mechanical index (MI) in the 300 kHz and 1MHz ultrasound. Several simulations indicated that bubble radius changes quickly from maximal value to zero by the driving frequency. Drug release was more efficient at 300 kHz compared to 1 MHz when MI was greater than 0.4. When the MI was less than 0.4, drug release was more efficient at 1 MHz compared to 300 kHz. The results demonstrate that ultrasound has a potential in enhancing drug release from liposome.

  7. Occurrence of cocaine in the air of the World's cities. An emerging problem? A new tool to investigate the social incidence of drugs?

    Science.gov (United States)

    Cecinato, Angelo; Balducci, Catia; Nervegna, Graziano

    2009-02-15

    The occurrence of illicit substances in the air was investigated in various world locations and ambient conditions. The analytical procedure optimized for cocaine, methadone and cocaethylene, based upon soxhlet extraction with organic solvent, clean-up through column chromatography, gas chromatographic separation and mass spectrometric detection, allowed the detection of the three compounds at levels as low as approximately 1 pg m(-3) in air samples of approximately 500 m3. Apart from Algiers, Algeria, and Pancevo, Serbia, cocaine was found in all cities investigated and its concentration ranged from picograms to nanograms/cubic meter (e.g., Rome, Italy, 22/97 pg m(-3); Santiago, Chile, 2.2/3.3 ng m(-3)). By contrast, the concentrations of methadone and cocaethylene in the air were always lower than the limit-of-detection allowed by the method. The procedure adopted was unsuitable for measuring cannabinoids and allowed only the identification of cannabinol. It was also poor in limit-of-detection with regards to heroin (35 pg m(-3)), however this compound could be identified in airborne particulates in Oporto, Portugal. Atmospheric concentrations of cocaine appeared to correlate to drug prevalence in the Italian regions investigated.

  8. Drug Facts

    Medline Plus

    Full Text Available ... Drug Use Hurts Kids Drug Use Hurts Unborn Children Drug Use Hurts Your Health Drug Use Hurts ... Find Treatment/Rehab Resources Prevent Drug Use Help Children and Teens Stay Drug-Free Talking to Kids ...

  9. Drug Facts

    Medline Plus

    Full Text Available ... Get Addicted to Drugs? Does Addiction Run in Families? Why Is It So Hard to Quit Drugs? ... Drug Use and Other People Drug Use and Families Drug Use and Kids Drug Use and Unborn ...

  10. [Antibacterial activity for clinical isolates from pediatric patients of clavulanic acid/amoxicillin (1: 14) -outcomes of special drug use investigation on antibacterial activity (annual changes)].

    Science.gov (United States)

    Ishida, Atsuko; Hasegawa, Naomi; Okano, Hideyuki; Hara, Terufumi; Yoshida, Pascal

    2013-06-01

    As a special drug use investigation, we monitored and assessed trends in antibacterial activity of clavulanic acid/amoxicillin (1:14) (hereafter, "CVA/AMPC (1:14)") and other antimicrobial agents for clinical isolates from pediatric patients with otitis media or respiratory, skin, and urinary tract infections. Against Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis isolated and identified from otorrhea, epipharynx and rhinorrhea of pediatric patients with otitis media, the MIC90s of CVA/AMPC (1:14) in five years between 2006-2010 were 1 microg/mL for S. pneumoniae and 8 microg/mL for H. influenzae and 0.25-0.5microg/mL for M catarrhalis. The changes of MIC90s of CVA/AMPC (1:14) for penicillin-resistant S. pneumoniae (PRSP) and beta-lactamase non-producing H. influenzae were two times, and no decrease in drug susceptibility was found in the period of the present investigation. In addition, the MIC changes of other antimicrobial agents for these three organisms were approximately two to four times as well. Against organisms isolated and identified from pus, sputum, pharynx, skin and urine of pediatric patients with respiratory, skin, and urinary tract infections, the MIC90s of CVA/AMPC (1:14) in four years between 2008-2011 were 1 microg/mL for S. pneumoniae, AMPC (1:14) were 2-8 microg/mL for S. aureus with a fourfold change, 2 microg/mL for methicillin-sensitive S. aureus without any change, 4-8 microg/mL for H. influenzae with a twofold change. Against beta-lactamase non-producing H. influenzae, MIC90s of CVA/AMPC (1:14) were 1 microg/mL for beta-lactamase negative ampicillin susceptible (BLNAS), 8 microg/mL for beta-lactamase negative ampicillin resistant (BLNAR), showing no change. Neither Streptococcus pyogenes or Klebsiella pneumoniae demonstrated any change and M. catarrhalis and Escherichia coli showed twofold changes of MIC90s of CVA/AMPC (1: 14). In the present investigation conducted to monitor annual changes in antibacterial

  11. Investigations on non-inferiority--the Food and Drug Administration draft guidance on treatments for nosocomial pneumonia as a case for exact tests for binomial proportions.

    Science.gov (United States)

    Röhmel, Joachim; Kieser, Meinhard

    2013-06-30

    This paper addresses statistical issues in non-inferiority trials where the primary outcome is a fatal event. The investigations are inspired by a recent Food and Drug Administration (FDA) draft guideline on treatments for nosocomial pneumonia. The non-inferiority margin suggested in this guideline for the endpoint all-cause mortality is defined on different distance measures (rate difference and odds ratio) and is discontinuous. Furthermore, the margin enables considerable power for the statistical proof of non-inferiority at alternatives that might be regarded as clinically unacceptable, that is, even if the experimental treatment is harmful as compared with the control. We investigated the appropriateness of the proposed non-inferiority margin as well as the performance of possible test statistics to be used for the analysis. A continuous variant of the margin proposed in the FDA guideline together with the unconditional exact test according to Barnard showed favorable characteristics with respect to type I error rate control and power. To prevent harmful new treatments from being declared as non-inferior, we propose to add a 'second hurdle'. We discuss examples and explore power characteristics when requiring both statistical significance and overcoming the second hurdle.

  12. A UK general practice population cohort study investigating the association between lipid lowering drugs and 30-day mortality following medically attended acute respiratory illness.

    Science.gov (United States)

    Joshi, Roshni; Venkatesan, Sudhir; Myles, Puja R

    2016-01-01

    Background. Cholesterol lowering drugs HMG-CoA reductase inhibitors (statins) and PPARα activators (fibrates) have been shown to reduce host inflammation via non-disease specific immunomodulatory mechanisms. Recent studies suggest that commonly prescribed drugs in general practice, statins and fibrates, may be beneficial in influenza-like illness related mortality. This retrospective cohort study examines the association between two lipid lowering drugs, statins and fibrates, and all-cause 30-day mortality following a medically attended acute respiratory illness (MAARI). Methods. Primary care patient data were retrospectively extracted from the UK Clinical Practice Research Datalink (CPRD) database. The sample comprised 201,179 adults aged 30 years or older experiencing a MAARI episode. Patient exposure to statins or fibrates was coded as separate dichotomous variables and deemed current if the most recent GP prescription was issued in the 30 days prior to MAARI diagnosis. Multivariable logistic regression and Cox regression were used for analyses. Adjustment was carried out for chronic lung disease, heart failure, metformin and glitazones, comorbidity burden, socio-demographic and lifestyle variables such as smoking status and body mass index (BMI). Statistical interaction tests were carried out to check for effect modification by gender, body mass index, smoking status and comorbidity. Results. A total of 1,096 (5%) patients died within the 30-day follow up period. Of this group, 213 (19.4%) were statin users and 4 (0.4%) were fibrate users. After adjustment, a significant 35% reduction in odds [adj OR; 0.65 (95% CI [0.52-0.80])] and a 33% reduction in the hazard [adj HR: 0.67 (95% CI [0.55-0.83])] of all-cause 30-day mortality following MAARI was observed in statin users. A significant effect modification by comorbidity burden was observed for the association between statin use and MAARI-related mortality. Fibrate use was associated with a non

  13. Investigation of novel superparamagnetic Ni0.5Zn0.5Fe2O4@albumen nanoparticles for controlled delivery of anticancer drug

    Science.gov (United States)

    Qasim, Mohd; Asghar, Khushnuma; Dharmapuri, Gangappa; Das, D.

    2017-09-01

    In the present work, multifunctional Ni0.5Zn0.5Fe2O4@albumen (NZF@Alb) and doxorubicin-loaded Ni0.5Zn0.5Fe2O4@albumen (NZF@Alb-Dox) core-shell nanoparticles have been prepared by a green and simple method using inexpensive chicken egg albumen and have been characterized for different physiochemical properties. The structural, morphological, thermal, and magnetic properties of the prepared nanoparticles have been investigated by an x-ray diffractometer, high-resolution transmission electron microscopy (HRTEM), field emission scanning electron microscopy, Fourier-transformed infrared, thermogravimetric analysis, and vibrating sample magnetometer techniques. Superparamagnetic Ni0.5Zn0.5Fe2O4 nanoparticles (NZF NPs) with the mean size ˜20 nm were coated with albumen matrix by an ultrasonication process. Inverse fast Fourier transform-assisted HRTEM micrographs and FTIR analysis revealed the coating of amorphous albumen on crystalline NZF NPs. NZF@Alb and NZF@Alb-Dox NPs have the mean size (D50) of ˜100 nm, good stability, and magnetic controllability. Magnetic measurements (field (H)-dependent magnetization (M)) show all samples to be super-paramagnetic in nature. Biocompatibilities of the NZF and NZF@Alb NPs were confirmed by in vitro 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay against RAW 264.7 cells. NZF@Alb NPs have been found to be more biocompatible than bare NZF. In Vitro Dox release behavior from NZF@Alb-Dox NPs has been studied at pH 7.4 and 5, and a sustained and pH-dependent drug release profile were observed. In vitro cytotoxicity or anticancer activity of the blank NZF@Alb NPs, free Dox, and NZF@Alb-Dox NPs against HeLa cells (cancer cell line) were also examined by MTT assay. The obtained results suggest that this scalable egg-albumen-based magnetic nanoformulation is suitable for targeted drug delivery applications. Thus, the present study could be extremely useful for the advancement of albumin-based nanocarrier design and

  14. Investigation and correlation of physical stability, dissolution behaviour and interaction parameter of amorphous solid dispersions of telmisartan: a drug development perspective.

    Science.gov (United States)

    Dukeck, R; Sieger, P; Karmwar, P

    2013-07-16

    The aim of this study was to investigate if amorphous solid dispersions of telmisartan, prepared in presence of different polymers, exhibit different structural and thermodynamic characteristics and whether these differences can be correlated to their physical stability (time to crystallisation) and dissolution behaviour. Amorphous samples were prepared by melt quenching. The resulting amorphous materials were characterised using X-ray diffraction, Raman spectroscopy and differential scanning calorimetry. All freshly prepared samples were completely X-ray amorphous (with a halo being the only feature in the diffractograms). The shape of the halos in the diffractograms varied suggesting structural variations in the near order of the molecules between the different amorphous solid dispersions (ASDs). Principal component analysis of the Raman spectra of the various ASD revealed that the samples clustered in the scores plot, again suggesting structural differences due to the presence of different drug-polymer interaction. The ranking of the samples with respect to physical stability and interaction parameter was: ASD of telmisartan:eudragit>ASD of telmisartan:soluplus>ASD of telmisartan:HPMC>ASD of telmisartan:PVP>amorphous telmisartan. The interaction parameter, calculated by using the Flory Huggins theory, showed a good correlation with the experimentally determined stability whereas a weak correlation was found with dissolution behaviour of different ASD. This study showed that correlation of physical stability and dissolution behaviour with calculated interaction parameter is possible for the same amorphous systems prepared by using different polymers. This could aid in selecting the most appropriate polymer for the development of optimised formulations containing amorphous drugs. It can be concluded that ASD prepared by using different polymers have different structural and thermal properties. These differences affect the physical stability and dissolution

  15. Post-marketing safety evaluation of the intravenous anti-influenza neuraminidase inhibitor peramivir: A drug-use investigation in patients with high risk factors.

    Science.gov (United States)

    Komeda, Takuji; Ishii, Shingo; Itoh, Yumiko; Sanekata, Masaki; Yoshikawa, Takayoshi; Shimada, Jingoro

    2016-10-01

    Peramivir, the only injectable anti-influenza neuraminidase inhibitor medically available in Japan at present, is considered first-line treatment in patients with high risk factors for influenza exacerbation. We conducted a drug-use investigation of peramivir in inpatients with high risk factors (old age, pregnancy, and underlying disease such as chronic respiratory disease) from January 2010 to March 2013. Data of 772 patients from 124 facilities across Japan were collected; peramivir's safety in 770 patients and effectiveness in 688 patients were examined. In total, 412 adverse events were observed in 219 patients (28.4%). Of these, 155 events were adverse drug reactions (ADRs) observed in 98 patients (12.7%). Major ADRs (≥2%) were increased aspartate aminotransferase (5.1%), increased alanine aminotransferase (3.8%) and decreased white blood cell count (2.5%). Fourteen serious ADRs were observed in 12 patients (1.6%). All serious ADRs were resolved or improved except for two events for which outcomes were unknown. Multivariate analyses revealed that ADR incidences were significantly associated with these four backgrounds of patients: medical history, no influenza vaccination, renal impairment and other infection(s). With regard to its effectiveness, the median time to alleviation of both influenza symptoms and fever was 3 days, including the first day of administration, which was the same as in other previous surveillance studies. This surveillance study indicated the safety of peramivir in the treatment of influenza inpatients with high risk factors under routine clinical settings. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  16. Extensively Drug-Resistant Klebsiella pneumoniae Causing Nosocomial Bloodstream Infections in China: Molecular Investigation of Antibiotic Resistance Determinants, Informing Therapy, and Clinical Outcomes

    Directory of Open Access Journals (Sweden)

    Wenzi Bi

    2017-06-01

    Full Text Available The rise in diversity of antimicrobial resistance phenotypes seen in Klebsiella pneumoniae is becoming a serious antibiotic management problem. We sought to investigate the molecular characteristics and clinical implications of extensively drug-resistant (XDR K. pneumoniae isolated from different nosocomial bloodstream infections (BSIs patients from July 2013 to November 2015. Even in combination treatment, meropenem did not protect against mortality of BSIs patients (P = 0.015. In contrast, tigecycline in combination with other antimicrobial agents significantly protected against mortality (P = 0.016. Antimicrobial susceptibility tests, molecular detection of antibiotic resistance determinants, conjugation experiments, multilocus sequence typing (MLST, S1-PFGE, Southern blot, SDS-PAGE, immunoblot analysis, and pulsed-field gel electrophoresis (PFGE were used to characterize these isolates. These XDR K. pneumoniae strains were resistant to conventional antimicrobials except tigecycline and polymyxin B and co-harbored diverse resistance determinants. rmtB, blaKPC−2 as well as blaCTX−M−9 were located on a transferable plasmid of ~54.2 kb and the most predominant replicon type was IncF. 23 of the 35 isolates belonging the predominant clone were found to incorporate the globally-disseminated sequence type ST11, but others including a unique, previously undiscovered lineage ST2281 (allelic profile: 4-1-1-22-7-4-35 were also found and characterized. The porins OmpK35 and OmpK36 were deficient in two carbapenemase-negative carbapenem-resistant strains, suggesting decreased drug uptake as a mechanism for carbapenem resistance. This study highlights the importance of tracking hospital acquired infections, monitoring modes of antibiotic resistance to improve health outcomes of BSIs patients and to highlight the problems of XDR K. pneumoniae dissemination in healthcare settings.

  17. A multiscale modeling approach to investigate molecular mechanisms of pseudokinase activation and drug resistance in the HER3/ErbB3 receptor tyrosine kinase signaling network.

    Science.gov (United States)

    Telesco, Shannon E; Shih, Andrew J; Jia, Fei; Radhakrishnan, Ravi

    2011-06-01

    Multiscale modeling provides a powerful and quantitative platform for investigating the complexity inherent in intracellular signaling pathways and rationalizing the effects of molecular perturbations on downstream signaling events and ultimately, on the cell phenotype. Here we describe the application of a multiscale modeling scheme to the HER3/ErbB3 receptor tyrosine kinase (RTK) signaling network, which regulates critical cellular processes including proliferation, migration and differentiation. The HER3 kinase is a topic of current interest and investigation, as it has been implicated in mechanisms of resistance to tyrosine kinase inhibition (TKI) of EGFR and HER2 in the treatment of many human malignancies. Moreover, the commonly regarded status of HER3 as a catalytically inactive 'pseudokinase' has recently been challenged by our previous study, which demonstrated robust residual kinase activity for HER3. Through our multiscale model, we investigate the most significant molecular interactions that contribute to potential mechanisms of HER3 activity and the physiological relevance of this activity to mechanisms of drug resistance in an ErbB-driven tumor cell in silico. The results of our molecular-scale simulations support the characterization of HER3 as a weakly active kinase that, in contrast to its fully-active ErbB family members, depends upon a unique hydrophobic interface to coordinate the alignment of specific catalytic residues required for its activity. Translating our molecular simulation results of the uniquely active behavior of the HER3 kinase into a physiologically relevant environment, our HER3 signaling model demonstrates that even a weak level of HER3 activity may be sufficient to induce AKT signaling and TKI resistance in the context of an ErbB signaling-dependent tumor cell, and therefore therapeutic targeting of HER3 may represent a superior treatment strategy for specific ErbB-driven cancers.

  18. Contact investigation after a fatal case of extensively drug-resistant tuberculosis (XDR-TB) in an aircraft, Germany, July 2013.

    Science.gov (United States)

    An der Heiden, Maria; Hauer, Barbara; Fiebig, Lena; Glaser-Paschke, Gisela; Stemmler, Markus; Simon, Claudia; Rüsch-Gerdes, Sabine; Gilsdorf, Andreas; Haas, Walter

    2017-03-23

    In July 2013, a passenger died of infectious extensively drug-resistant tuberculosis (XDR-TB) on board of an aircraft after a 3-hour flight from Turkey to Germany. Initial information indicated the patient had moved about the aircraft coughing blood. We thus aimed to contact and inform all persons exposed within the aircraft and to test them for newly acquired TB infection. Two-stage testing within 8 weeks from exposure and at least 8 weeks after exposure was suggested, using either interferon gamma release assays (IGRAs) or tuberculin skin test (TST). The TST cut-off was defined at a diameter > 10 mm; for differentiation between conversion and boosting, conversion was defined as increase of skin induration > 5 mm. Overall, 155 passengers and seven crew members were included in the investigation: the questionnaire response rate was 83%; 112 (69%) persons were tested at least once for TB infection. In one passenger, who sat next to the area where the patient died, a test conversion was registered. As of March 2017, no secondary active TB cases have been reported. We describe an unusual situation in which we applied contact tracing beyond existing European guidelines; we found one latent tuberculosis infection in a passenger, which we consider probably newly acquired. This article is copyright of The Authors, 2017.

  19. Investigation of the influence of EPs® 7630, a herbal drug preparation from Pelargonium sidoides, on replication of a broad panel of respiratory viruses.

    Science.gov (United States)

    Michaelis, Martin; Doerr, Hans Wilhelm; Cinatl, Jindrich

    2011-03-15

    The Pelargonium sidoides extract EPs® 7630 is an approved drug for the treatment of acute bronchitis in Germany. The postulated mechanisms underlying beneficial effects of EPs® 7630 in bronchitis patients include immunomodulatory and cytoprotective effects, inhibition of interaction between bacteria and host cells, and increase of cilliary beat frequency on respiratory cells. Here, we investigated the influence of EPs® 7630 on replication of a panel of respiratory viruses. Determination of virus-induced cytopathogenic effects and virus titres revealed that EPs® 7630 at concentrations up to 100 μg/ml interfered with replication of seasonal influenza A virus strains (H1N1, H3N2), respiratory syncytial virus, human coronavirus, parainfluenza virus, and coxsackie virus but did not affect replication of highly pathogenic avian influenza A virus (H5N1), adenovirus, or rhinovirus. Therefore, antiviral effects may contribute to the beneficial effects exerted by EPs® 7630 in acute bronchitis patients.

  20. Pharmacokinetic-pharmacodynamic analyses of antihypertensive drugs, nifedipine and propranolol, in spontaneously hypertensive rats to investigate characteristics of effect and side effects.

    Science.gov (United States)

    Kiriyama, Akiko; Honbo, Akino; Nishimura, Asako; Shibata, Nobuhito; Iga, Katsumi

    2016-04-01

    To investigate the relationship between the pharmacokinetics (PK) and effects and/or side-effects of nifedipine and propranolol, simultaneous examination of their PK and pharmacodynamics (PD), namely blood pressure (BP), heart rate (HR), and QT interval (QT), were assessed in spontaneously hypertensive rats as a disease model. Drugs were infused intravenously for 30 min, then plasma PK and hemodynamic effects were monitored. After general two-compartmental analysis was applied to the plasma data, PD parameters were calculated by fitting the data to PK-PD models. After nifedipine administration, the maximal hypotensive effect appeared about 10 min after starting the infusion, then BP started to elevate although the plasma concentration increased, supposedly because of a negative feedback mechanism generated from the homeostatic mechanism. After propranolol administration, HR decreased by half, and this bradycardic effect was greater than that with nifedipine. Wide variation in QT was observed when the propranolol concentration exceeded 700 ng/mL. This variation may have been caused by arrhythmia. Prolongation of QT with propranolol was greater than that with nifedipine, and bradycardia was slower than the concentration increase and QT prolongation. The characteristically designed PK-PD model incorporating a negative feedback system could be adequately and simultaneously fitted to both observed effect and side-effects.

  1. Drug Facts

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    Full Text Available ... Addiction? Addiction Risk Factors Does Addiction Run in Families? Why Is It So Hard to Quit Drugs? ... Drug Use Hurts Other People Drug Use Hurts Families Drug Use Hurts Kids Drug Use Hurts Unborn ...

  2. Drug Facts

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    Full Text Available ... Use Hurts Unborn Children Drug Use Hurts Your Health Drug Use Hurts Bodies Drug Use Hurts Brains Drug Use and Mental Health Problems Often Happen Together The Link Between Drug ...

  3. 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, ...

  4. Drug Facts

    Medline Plus

    Full Text Available ... Addiction? Addiction Risk Factors Does Addiction Run in Families? Why Is It So Hard to Quit Drugs? ... Drug Use Hurts Other People Drug Use Hurts Families Drug Use Hurts Kids Drug Use Hurts Unborn ...

  5. Drug Facts

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    Full Text Available ... The Link Between Drug Use and HIV/AIDS Recovery & Treatment Drug Treatment Facts Does Drug Treatment Work? ... and Family Can Help Find Treatment/Rehab Resources Prevent Drug Use Help Children and Teens Stay Drug- ...

  6. Hepatocytes--the choice to investigate drug metabolism and toxicity in man: in vitro variability as a reflection of in vivo.

    Science.gov (United States)

    Gómez-Lechón, María José; Castell, José Vicente; Donato, María Teresa

    2007-05-20

    The pharmaceutical industry is committed to marketing safer drugs with fewer side effects, predictable pharmacokinetic properties and quantifiable drug-drug interactions. Drug metabolism is a major determinant of drug clearance and interindividual pharmacokinetic differences, and an indirect determinant of the clinical efficacy and toxicity of drugs. Progressive advances in the knowledge of metabolic routes and enzymes responsible for drug biotransformation have contributed to understanding the great metabolic variations existing in human beings. Phenotypic as well genotypic differences in the expression of the enzymes involved in drug metabolism are the main causes of this variability. However, only a minor part of phenotypic variability in man is attributable to gene polymorphisms, thus making the definition of a normal liver complex. At present, the use of human in vitro hepatic models at early preclinical stages means that the process of selecting drug candidates is becoming much more rational. Cultured human hepatocytes are considered to be the closest model to human liver. However, the fact that hepatocytes are located in a microenvironment that differs from that of the cell in the liver raises the question: to what extent does drug metabolism variability observed in vitro actually reflect that of the liver in vivo? By comparing the metabolism of a model compound both in vitro and in vivo in the same individual, a good correlation between the in vitro and in vivo relative abundance of oxidized metabolites and the hydrolysis of the compound was observed. Thus, it is reasonable to consider that the variability observed in human hepatocytes reflects the existing phenotypic heterogeneity of the P450 expression in human liver.

  7. Principal component analysis as a tool for library design: a case study investigating natural products, brand-name drugs, natural product-like libraries, and drug-like libraries.

    Science.gov (United States)

    Wenderski, Todd A; Stratton, Christopher F; Bauer, Renato A; Kopp, Felix; Tan, Derek S

    2015-01-01

    Principal component analysis (PCA) is a useful tool in the design and planning of chemical libraries. PCA can be used to reveal differences in structural and physicochemical parameters between various classes of compounds by displaying them in a convenient graphical format. Herein, we demonstrate the use of PCA to gain insight into structural features that differentiate natural products, synthetic drugs, natural product-like libraries, and drug-like libraries, and show how the results can be used to guide library design.

  8. Investigation into Self-Medication of Drugs for Primary and Adjunct Therapy in Psychiatric Diseases Among Students in Chittagong City of Bangladesh: A Comparison Between Medical and Nonmedical Students

    Science.gov (United States)

    Chowdhury, Nishat; Haque, Ahsanul; Aysha, Farjana

    2012-01-01

    Background: All kinds of drugs are available over the counter in Bangladesh. Aim: The objective of this study was to investigate the over the counter use of self medicated drugs for primary and adjunct therapy in psychiatric diseases among medical and nonmedical students. Materials and Methods: 101 medical students and 186 nonmedical students were found, who used at least one of the nine drugs (believed as antipsychotics among nonmedical people) under survey within 6 months prior to survey date. The nine drugs used for survey were domperidone, sertraline, amitriptyline, midazolam, diazepam, prochlorperazine bromazepam, flupentixol–melitracen, and clonazepam. Statistical Analysis: Snowball sampling method was used. The symptoms, diseases, etc. of the students and the length of therapies they had followed for the respective drugs were noted. Results: Among nonmedical students, several cases were found where drugs were being self medicated in wrong indications, for example, use of flupentixol melitracen and domperidone to treat headache. Conclusion: The nonmedical students chose the fast acting drugs having the strongest effects for self medication. PMID:23723537

  9. Investigation into Self-Medication of Drugs for Primary and Adjunct Therapy in Psychiatric Diseases Among Students in Chittagong City of Bangladesh: A Comparison Between Medical and Nonmedical Students

    Directory of Open Access Journals (Sweden)

    Nishat Chowdhury

    2012-01-01

    Full Text Available Background: All kinds of drugs are available over the counter in Bangladesh. Aim: The objective of this study was to investigate the over the counter use of self medicated drugs for primary and adjunct therapy in psychiatric diseases among medical and nonmedical students. Materials and Methods: 101 medical students and 186 nonmedical students were found, who used at least one of the nine drugs (believed as antipsychotics among nonmedical people under survey within 6 months prior to survey date. The nine drugs used for survey were domperidone, sertraline, amitriptyline, midazolam, diazepam, prochlorperazine bromazepam, flupentixol-melitracen, and clonazepam. Statistical Analysis: Snowball sampling method was used. The symptoms, diseases, etc. of the students and the length of therapies they had followed for the respective drugs were noted. Results: Among nonmedical students, several cases were found where drugs were being self medicated in wrong indications, for example, use of flupentixol melitracen and domperidone to treat headache. Conclusion: The nonmedical students chose the fast acting drugs having the strongest effects for self medication.

  10. Investigation and drug sensitivity analysis of urinary tract fungal infections in hospital%尿路真菌感染调查与药敏分析

    Institute of Scientific and Technical Information of China (English)

    胡跃世; 李鹏; 曹志华; 刘磊; 王阳

    2016-01-01

    目的 探讨尿路医院感染真菌的分布与对抗真菌药物的敏感性,为临床合理选择抗真菌药物治疗提供指导.方法 收集2013年7月-2015年7月医院收治的经中段尿细菌培养确诊为尿路真菌感染的237例患者为研究对象,采集患者尿液标本,检出的菌株采用科玛嘉显色培养基进行鉴定,并通过ATBFUNGUS3真菌药敏试剂进行药物敏感性试验.结果 清洁中段尿标本,经真菌培养后分离得到237株真菌,白色假丝酵母菌113株占47.68%,光滑假丝酵母菌79株占33.33%;患者主要集中在综合IC U、泌尿外科、心内科、内分泌科及呼吸内科,以上科室尿路真菌感染占83.12%;白色假丝酵母菌、光滑假丝酵母菌及热带假丝酵母菌对两性霉素B和氟胞嘧啶敏感,耐药率分别为0和0.88%、1.27%和0、0和0,白色假丝酵母菌对氟康唑、伊曲康唑以及伏立康唑的耐药率均10.00%,克柔假丝酵母菌主要对氟胞嘧啶敏感,对伊曲康唑耐药率38.4%,对伏立康唑的耐药率30.7%.结论 白色假丝酵母菌、光滑假丝酵母菌以及热带假丝酵母菌是院内尿路真菌感染的主要真菌,其对氟胞嘧啶以及两性霉素B具有较好的敏感性.%OBJECTIVE To investigate the distribution and drug susceptibility of urinary tract fungal infections in hospital ,so as to provide guidance for clinical rational selection of antimicrobial agents against infections . METHODS Totally 237 patients with urinary tract fungal infections were collected who were diagnosed by middle section urine bacterial culture from Jul .2013 to Jul .2015 .Strains were identified with CHROMagar ,and the drug susceptibility test was performed with ATBFUNGUS3 reagent .RESULTS A total of 237 strains of fungi were isolated ,including 113 strains of Candida albicans (47 .68% ) and 79 strains of Canadida glabrata (33 .33% ) . The fungi were mainly found in departments of integrated ICU ,urology ,cardiology ,endocrinology and respirato

  11. Comparison of Occlusive and Open Application in a Psoriasis Plaque Test Design, Exemplarily Using Investigations of Mapracorat 0.1% Ointment versus Vehicle and Reference Drugs.

    Science.gov (United States)

    Wigger-Alberti, Walter; Williams, Ragna; von Mackensen, Yi-Ling; Hoffman-Wecker, Maciej; Grossmann, Ulrike; Staedtler, Gerald; Nkulikiyinka, Richard; Shakery, Kaweh

    2017-01-01

    Psoriasis plaque tests (PPTs) are important tools in the early phases of antipsoriatic drug development. Two distinct PPT design variants (open vs. occluded drug application) are commonly used, but no previous work has aimed to directly compare and contrast their performance. We compared the antipsoriatic efficacy of mapracorat 0.1% ointment and reference drugs reported in 2 separate studies, representing open and occluded PPT designs. The drug effect size was measured by sonography (mean change in echo-poor band thickness), chromametry, and standardized clinical assessment. Antipsoriatic effects were detectable for the study drugs in both occluded and open PPTs. Differences between the potency of antipsoriatic drugs and vehicle were observable. The total antipsoriatic effect size appeared to be higher in the occluded PPT than the open PPT, despite the shorter treatment duration (2 vs. 4 weeks). Effect dynamics over time revealed greater differences between some study drugs in the open PPT compared to the occluded PPT. Taking the higher technical challenges for the open PPT into account, we recommend the occluded PPT as a standard screening setting in early drug development. In special cases, considering certain drug aspects or study objectives that would require procedural adaptations, an open PPT could be the better-suited design. Finally, both PPT models show clear advantages: classification as phase I studies, small number of psoriatic subjects, relatively short study duration, excellent discrimination between compounds and concentrations, parallel measurement of treatment response, and go/no go decisions very early in clinical development. © 2017 S. Karger AG, Basel.

  12. Effect of Drug Loading Method on Drug Content and Drug Release from Calcium Pectinate Gel Beads

    OpenAIRE

    2010-01-01

    Drug-loaded calcium pectinate gel (CaPG) beads were prepared by either mixing, absorption, or swelling method. The effects of drug loading method as well as the drug loading factors (i.e., drug concentration, soaking time in drug solution, type of solvent) on drug content and drug release were investigated. The amount of drug uptake (i.e., drug content) into CaPG beads increased as the initial drug concentration increased and varied depending on the loading method. The in vitro release studie...

  13. Drugs and Drug Abuse.

    Science.gov (United States)

    Anastas, Robert, Comp.; And Others.

    GRADES OR AGES: Secondary grades. SUBJECT MATTER: Drugs and drug abuse. ORGANIZATION AND PHYSICAL APPEARANCE: The guide is divided into several sections, each of which is in outline or list form. It is xeroxed and spiral-bound with a paper cover. OBJECTIVES AND ACTIVITIES: No objectives are mentioned. The major portion of the guide contains a…

  14. 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 ...

  15. An Empirical Study of the Construction of Professional Force for Food and Drug Crime Investigation%食品药品犯罪侦查专业力量建设实证研究

    Institute of Scientific and Technical Information of China (English)

    陈涛

    2015-01-01

    With the food and drug crimes being rampant, creating a professional investigation force is undoubtedly the key measure to solve this problem. Although there is much controversy over the formation of a professional investigation force for food and drug crime investigation team, but the food and drug security is the foundation of people's life and health, social development, national stability. Therefore, in order to solve the problems in food and drug crime investigation, this article analyzes the causes of the problems and puts forward the necessity of constructing a professional investigation team by interpreting the current situation of food and drug crime investigation team on the basis of empirical researches.%在食品药品犯罪猖獗的情形下,构建专业的侦查力量无疑是解决问题的关键。虽然目前对组建专业食品药品犯罪侦查队伍还存在争议,但是食品药品安全在保障人民群众生命健康、社会发展、国家稳定中的基础地位是不言而喻的。为此,在实证调研的基础上,通过剖析目前食品药品犯罪案件侦查的队伍现状,分析问题产生的原因,论证建设专业侦查队伍的必要性,以期解决食品药品犯罪侦查中的瓶颈。

  16. Investigation on the ion pair amphiphiles and their in vitro release of amantadine drug based on PLGA–PEG–PLGA gel

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Xiaoxia, E-mail: yxx-678@163.com; Ji, Xiaoqing; Shi, Chunhuan; Liu, Jing [Shandong University, School of Pharmaceutical Science and Center for Pharmaceutical Research & Drug Delivery Systems (China); Wang, Haiyang [Institute of Materia Medica Shandong Academy of Medical Sciences, Shandong Taitian Newdrug Discovery Co.Ltd (China); Luan, Yuxia, E-mail: yuxialuan@sdu.edu.cn [Shandong University, School of Pharmaceutical Science and Center for Pharmaceutical Research & Drug Delivery Systems (China)

    2014-12-15

    The amantadine drug and oleic acid surfactant are used to form amantadine-based ion pair amphiphiles based on proton transfer reaction between the drug and the surfactant molecules. The ion pair amphiphiles are characterized by {sup 1}H-nuclear magnetic resonance, Fourier transform infrared spectroscopy, and X-ray diffraction. Self-assembly properties of amantadine-based ion pair amphiphiles are studied by surface tension determination, transmission electron microscopy, zeta potential, and dynamic light scattering. The aggregation behavior studies indicate that the as-prepared ion pair amphiphiles can self-assemble into vesicles with the size of 200–300 nm in aqueous solution. The drug release results show that the amantadine release rate could be well controlled by incorporating the amantadine-based ion pair vesicles in poly (lactic-co-glycolic acid)-poly (ethylene glycol)-poly (lactic-co-glycolic acid) (PLGA–PEG–PLGA) copolymer hydrogel. The drug release from the AT–OA vesicle-loaded PLGA–PEG–PLGA hydrogel is significantly inhibited in comparison with the AT-loaded PLGA–PEG–PLGA hydrogel. The present work thus demonstrates that the vesicle-loaded hydrogel is a good candidate for the drug delivery system with long-term controlled drug release behavior.

  17. Stigma and Human Rights Abuses against People Who Inject Drugs in Russia--A Qualitative Investigation to Inform Policy and Public Health Strategies.

    Directory of Open Access Journals (Sweden)

    Karsten Lunze

    Full Text Available Drug policing practices in the Russian Federation (Russia are often punitive and have been shown to be associated with HIV risk behaviors among people who inject drugs (PWID. Less is known about strategies to address the problem in that setting, where substance use stigma is highly persistent. A better understanding of forms, causes and consequences of drug policing in Russia could inform drug policy in a context of substantial policy resistance. This qualitative study's goal is to characterize the phenomenon of police involvement with Russian PWID and to explore strategies for drug policing in the Russian country context.Using a semi-structured interview guide, we collected data from a purposive sample of 23 key informants including PWID, police officers, and experts from civil society and international organizations in Russia. We used a thematic analysis approach to inductively generate new insight into the phenomenon of police involvement and potential strategies to address it.Policing practices involving PWID include unjustified arrests, planting of false evidence and extrajudicial syringe confiscations, and often constitute human rights violations. Russian PWID personally experienced police violence as ubiquitous, taking on various forms such as beating, unjustified arrests, verbal harassment, and coercion. The persistent societal stigma dehumanizes PWID, and such stigmatization facilitates police abuse. To address stigma and overcome the PWID-police adversity, study participants suggested fostering a mutual understanding between the police and public health sectors.Participants describe substantial human rights violations as part of policing illicit drug use in Russia. Police should include principles of effective prevention of substance use and HIV risk reduction in their trainings. Alignment of public safety and public health goals could address drug use-related risks and HIV prevention among key populations in Russia.

  18. 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 ...

  19. 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 ...

  20. Drug Facts

    Medline Plus

    Full Text Available ... Nicotine Facts Other Drugs of Abuse What is Addiction? Do You or a Loved One Have a Drug Use Problem? Signs of Drug Use and Addiction How Does Drug Use Become Addiction? Addiction Risk ...

  1. Drug Facts

    Medline Plus

    Full Text Available ... Drug Use and Your Health Other Effects on the Body Drug Use Hurts Brains Drug Use and Mental Health Problems Often Happen Together The Link Between Drug Use and HIV/AIDS Treatment & ...

  2. Investigation of standardized administration of anti-platelet drugs and its effect on the prognosis of patients with coronary heart disease.

    Science.gov (United States)

    Ding, Chao; Zhang, Jianhua; Li, Rongcheng; Wang, Jiacai; Hu, Yongcang; Chen, Yanyan; Li, Xiannan; Xu, Yan

    2017-10-01

    The aim of the present study was to explore the effect of adherence to standardized administration of anti-platelet drugs on the prognosis of patients with coronary heart disease. A total of 144 patients newly diagnosed with coronary heart disease at Lu'an Shili Hospital of Anhui Province (Lu'an, China) between June 2010 and June 2012 were followed up. Kaplan-Meier curves and the Cox regression model were used to evaluate the effects of standardized administration of anti-platelet drugs on primary and secondary end-point events. Of the patients with coronary heart disease, 109 (76%) patients took standard anti-platelet drugs following discharge. Kaplan-Meier curve and Cox regression analysis showed that standardized administration of anti-platelet drugs reduced the risk of primary end-point events (including all-cause mortality, non-lethal myocardial infarction and stroke) of patients with coronary heart disease [hazard ratio (HR)=0.307; 95% confidence interval (CI): 0.099-0.953; P=0.041) and all-cause mortality (HR=0.162; 95% CI: 0.029-0.890; P=0.036); however, standardized administration had no predictive value with regard to secondary end-point events. Standardized administration of anti-platelet drugs obviously reduced the risk of primary end-point events in patients with coronary heart disease, and further analysis showed that only all-cause mortality exhibited a statistically significant reduction.

  3. Investigation and Analysis of the Perception of Patients on Drug Interaction in Our Hospital%我院就医患者对药物相互作用的认知度调查与分析

    Institute of Scientific and Technical Information of China (English)

    刘萍; 陈玉文; 何新荣; 赵庆大

    2011-01-01

    OBJECTIVE: To investigate the perception of patients on drug interaction in our hospital and to provide reference for improving rational use of drugs.METHODS: By questionnaire survey, outpatients of our hospital during May.-Jun.in 2008 were investigated.200 questionnaires involved the number of drug category, drug interaction cognition, drug interaction knowledge, consulting object who answered how to use drugs rationally after getting drugs and case investigation.RESULTS: A total of 178 valid questionaires were collcted.Patients who took 1~5 kinds of drugs accounted for 53.37 %, and the proportion of people who understood the drug interaction was 23.03%.85.40% of patients wanted to discern the drug-drug interaction.No one believed that they should consult clinical pharmacists.In case investigation, more than half of patients didn' t understand drug interaction.CONCLUSION: In our hospital, patients have low perception on drug interaction.Great importance should be attached to it and relevant measures should be conducted.%目的:了解我院惠者对药物相互作用的认知度现状,为促进合理用药提供依据.方法:采用问卷调查方式,对我院2008年5-6月就医的门诊患者进行调查,共发放200份问卷,内容包括就医患者服药种数、对药物相互作用了解程度、对药物相互作用知识的需求、取药后会向谁咨询如何合理用药的问题等,以及常见药物相互作用的实例调查.结果:共回收有效问卷178份,其中就医患者中服药1~5种的占被调查人数的53.37%;但对药物相互作用了解的仅占23.03%;有85.40%的人对药物相互作用知识有需求;取药后认为应向临床药师咨询的比例为0;在常见药物相互作用实例调查中,不了解者超过了半数.结论:我院就医患者对药物相互作用认知度不高,应予重视并采取相关措施.

  4. 我院抗肿瘤辅助药临床应用现状调查与分析%Investigation and Analysis of Clinical Application of Anti-tumor Adjuvant Drugs in Our Hospital

    Institute of Scientific and Technical Information of China (English)

    苗秋丽; 宋燕青; 张文锐; 张维伟; 张四喜

    2015-01-01

    OBJECTIVE:To provide a reference for clinical use of anti-tumor adjuvant drugs as is reasonable,effective and economical. METHODS:By retrospective investigation and analysis,the utilization of anti-tumor adjuvant drugs in the oncology department of our hospital during 2010 and 2013 was analyzed statistically in respect of the type,dosage form,consumption amount,DDDs,DDC,DUI etc. RESULTS:The anti-tumor adjuvant drugs in our hospital were dominated by injections,especial-ly domestic drugs,the consumption amount of which accounted for 80% of the total consumption amount of anti-tumor adjuvant drugs each year. The anti-tumor adjuvant drugs were mainly used for symptomatic treatment of various adverse reactions. Drug syn-chronization was relatively good each year,however,excessive use of individual drugs existed. CONCLUSIONS:Anti-tumor adju-vant drugs have relatively better synchronism in the drugs quantities and medication number. However,individual drugs have exces-sive use and other irrational use.%目的:为临床合理、有效、经济地选用抗肿瘤辅助药提供参考。方法:采用回顾性调查方法,对2010-2013年我院肿瘤科抗肿瘤辅助药品种、剂型、销售金额、用药频度、日均费用、药物利用指数等进行统计分析。结果:我院抗肿瘤辅助药以注射剂为主;国产药各年度销售金额占抗肿瘤辅助药总销售金额比例均达80%左右;抗肿瘤辅助药主要为对症处理各种不良反应,各年度药品同步性较好,但个别药品存在超量使用情况。结论:抗肿瘤辅助药购药数量与用药人数同步性较好,但个别药物存在超量使用等不合理用药现象。

  5. 新药研发市场导向性量表研究%Investigation on market-orientation scale of new drug research & development

    Institute of Scientific and Technical Information of China (English)

    孟光兴; 鲁汉玲; 沈枫

    2013-01-01

    目的:探索定量测量新药研发市场导向性的方法,为定量研究新药研发活动市场导向性提供可信、有效的量表.方法:实地调研12家新药研发绩效较好的制药企业,对新药研发市场导向性的要素及特征进行经验性总结;结合市场导向与新药研发相关理论研究,建立新药研发市场导向性量表,并对量表的信度、效度进行检验.结果与结论:建立的量表具有较好的信度、效度.%Objective: To explore the quantitative measurement of market-oriented character of drug research & development, and provide a credible and effective scale for quantitative study of new drug reasearch & development activities. Methods: Twelve pharmaceutical companies which have good performance in new drug reasearch & development were surveyed, and the market-oriented elements and features of new drug reasearch & development were empirically summarized; combining with theoretical studies of market-orientation and new drug reasearch & development, a market-oriented scale of new drug reasearch & development was established, and its validity and reliability was verified. Result and Conclusion; The scale has good reliability and validity.

  6. An investigation into the influence of drug-polymer interactions on the miscibility, processability and structure of polyvinylpyrrolidone-based hot melt extrusion formulations.

    Science.gov (United States)

    Chan, Siok-Yee; Qi, Sheng; Craig, Duncan Q M

    2015-12-30

    While hot melt extrusion is now established within the pharmaceutical industry, the prediction of miscibility, processability and structural stability remains a pertinent issue, including the issue of whether molecular interaction is necessary for suitable performance. Here we integrate the use of theoretical and experimental drug-polymer interaction assessment with determination of processability and structure of dispersions in two polyvinylpyrrolidone-based polymers (PVP and PVP vinyl acetate, PVPVA). Caffeine and paracetamol were chosen as model drugs on the basis of their differing hydrogen bonding potential with PVP. Solubility parameter and interaction parameter calculations predicted a greater miscibility for paracetamol, while ATR-FTIR confirmed the hydrogen bonding propensity of the paracetamol with both polymers, with little interaction detected for caffeine. PVP was found to exhibit greater interaction and miscibility with paracetamol than did PVPVA. It was noted that lower processing temperatures (circa 40°C below the Tg of the polymer alone and Tm of the crystalline drug) and higher drug loadings with associated molecular dispersion up to 50% w/w were possible for the paracetamol dispersions, although molecular dispersion with the non-interactive caffeine was noted at loadings up to 20% w./w. A lower processing temperature was also noted for caffeine-loaded systems despite the absence of detectable interactions. The study has therefore indicated that theoretical and experimental detection of miscibility and drug-polymer interactions may lead to insights into product processing and extrudate structure, with direct molecular interaction representing a helpful but not essential aspect of drug-polymer combination prediction.

  7. Identification of ten new designer drugs by GC-MS, UPLC-QTOF-MS, and NMR as part of a police investigation of a Danish internet company

    DEFF Research Database (Denmark)

    Reitzel, Lotte A; Dalsgaard, Petur Weihe; Müller, Irene B;

    2012-01-01

    The ability of forensic laboratories to detect and identify unknown compounds is highly important since new, non-controlled designer drugs are appearing on the market with increasing frequency. In this study, the combined use of gas chromatography-mass spectrometry (GC-MS) and ultra performance...... liquid chromatography-quadrupole time of flight-mass spectrometry (UPLC-QTOF-MS) was used for screening of new unknowns. In one large seizure from a Danish Internet company, ten different drugs were identified. Several of the compounds were seized for the first time in Denmark. The GC-MS and UPLC...

  8. [Investigation on pattern of quality control for Chinese materia medica based on famous-region drug and bioassay--the work reference].

    Science.gov (United States)

    Yan, Dan; Xiao, Xiaohe

    2011-05-01

    Selection and standardization of the work reference are the technical issues to be faced with in the bioassay of Chinese materia medica. Taking the bioassay of Coptis chinensis. as an example, the manufacture process of the famous-region drugs extraction was explained from the aspects of original identification, routine examination, component analysis and bioassay. The common technologies were extracted, and the selection and standardization procedures of the work reference for the bioassay of Chinese materia medica were drawn up, so as to provide technical support for constructing a new mode and method of the quality control of Chinese materia medica based on the famous-region drugs and bioassay.

  9. 门诊药房易混淆药品调查与对策分析%Investigation and Countermeasures on Drug Confusion in Outpatient Pharmacy

    Institute of Scientific and Technical Information of China (English)

    王慧

    2016-01-01

    Objective:To guarantee the safe use of easy-to-confuse drugs, avoid accidents, so as to improve the level of pharmacy administration.Methods: The situation of easy to confuse drugs in our pharmacy during 2014 was statistically classiifed, and the preventive measures were put forwardResults: A variety of reasons leading to drug dispensing errors were found, including similar generic names and outer packagings, the same generic names with different dosage forms, etc.Conclusion: To strengthen the management of similar drugs; to strictly comply with the "four check ten pairs" and other standard operating procedures during dispensing; to place neatly these easy-to-confuse drugs by category and location with obvious identiifcation; to post warning signs for similar drugs; to carefully check the patient information in the delivery of drugs, as well as the usage and dosage;to regularly check the numbers of similar drugs. The above measures can greatly reduce the risk of errors in dispensing personnel, and improve the safety management level.%目的:保障易混淆药品用药安全,避免差错事故,提升药事管理水平。方法:对本院门诊药房2014年度易混淆药品进行分类统计,提出防范措施。结果:通过调查与分析,找出导致药品调剂差错的多种原因,即通用名相似、外包装相似、通用名相同但剂型规格不同等。结论:应加强相似药品管理,药师调配时严格遵守“四查十对”等标准操作规程;易混淆药品分区摆放;相似药品张贴警示标识;药师在交付药品时仔细核对患者信息,进一步核对用法用量;定时清点相似药品数量。以上措施可大大减少调剂人员发生差错的几率,提高安全用药管理水平。

  10. Exposure of drugs for hypertension, diabetes, and autoimmune disease during pregnancy and perinatal outcomes: an investigation of the regulator in Japan.

    Science.gov (United States)

    Sato, Ryosuke; Ikuma, Mutsuhiro; Takagi, Kazunori; Yamagishi, Yoshiaki; Asano, Junichi; Matsunaga, Yusuke; Watanabe, Hiroshi

    2015-01-01

    Assessment of perinatal effects of drug exposure during pregnancy after approval is an important issue for regulatory agencies. The study aimed to explore associations between perinatal outcomes and maternal exposure to drugs for chronic diseases, including hypertension, diabetes, and autoimmune disease.We reviewed 521 cases of adverse reactions due to drug exposure during pregnancy who were reported to the Pharmaceuticals and Medical Devices Agency, a regulatory authority in Japan. The primary outcomes were fetal and neonatal death and malformation of infants. Associations between perinatal outcomes and exposure to each drug category for hypertension, diabetes, and autoimmune disease were evaluated using logistic regression analysis.Of the 521 cases (maternal age: 15-47 years; mean 32.3 ± 5.5), fetal and neonatal deaths were reported in 159 cases (130 miscarriage; 12 stillbirth; 4, neonatal death; and 13 abortion due to medical reasons), and malformations of infants were observed in 124 cases. In contrast to the trend of association between diabetes with or without medication and fetal and neonatal death (odds ratio [OR], 0.49; 95% confidence interval [CI], 0.17-1.36), exposure to oral antidiabetics tended to be associated with fetal and neonatal death (OR, 4.86; 95% CI, 0.81-29.2). Malformation tended to be correlated with exposure to angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (OR, 2.98; 95% CI, 0.76-11.7). This association showed trends opposite to that of the association with hypertension itself (OR, 0.42; 95% CI, 0.18-1.02) or overall antihypertensives (OR, 0.42; 95% CI, 0.15-1.13). Occurrence of multiple malformations was associated with exposure to biologics (OR, 8.46; 95% CI, 1.40-51.1), whereas there was no significant association between multiple malformations and autoimmune disease with or without medication (OR 1.07; 95% CI, 0.37-3.06).These findings suggest that drugs of different categories may have undesirable

  11. FDA relations during drug development

    OpenAIRE

    Mitchel, Jules T.

    2000-01-01

    Working closely and cooperatively with regulatory authorities during drug development is vital to successful drug development programs. In the United States, the drug development team includes not only members of the key disciplines of drug discovery, clinical research, regulatory affairs, marketing, chemistry, toxicology, and legal aspects, but also the Food and Drug Administration (FDA). New regulations encourage meetings at the pre-investigational new drug (pre-IND), end-of-phase-2, and pr...

  12. Epigenetic Drugs for Multiple Sclerosis

    OpenAIRE

    Peedicayil, Jacob

    2016-01-01

    There is increasing evidence that abnormalities in epigenetic mechanisms of gene expression contribute to the development of multiple sclerosis (MS). Advances in epigenetics have given rise to a new class of drugs, epigenetic drugs. Although many classes of epigenetic drugs are being investigated, at present most attention is being paid to two classes of epigenetic drugs: drugs that inhibit DNA methyltransferase (DNMTi) and drugs that inhibit histone deacetylase (HDACi). This paper discusses ...

  13. Metallomics for drug development: an integrated CE-ICP-MS and ICP-MS approach reveals the speciation changes for an investigational ruthenium(III) drug bound to holo-transferrin in simulated cancer cytosol.

    Science.gov (United States)

    Aleksenko, Svetlana S; Matczuk, Magdalena; Lu, Xifeng; Foteeva, Lidia S; Pawlak, Katarzyna; Timerbaev, Andrei R; Jarosz, Maciej

    2013-08-01

    A method based on combining inductively coupled plasma mass spectrometry (ICP-MS) with capillary electrophoresis (CE) or an ultrafiltration step was developed to study the speciation of the serum-protein adducts of a ruthenium anticancer drug under in vitro intracellular conditions. The formation of a reactive Ru species in the cell, following the metal release from the protein, is thought to play an important role in the drug's mode of action. Glutathione and ascorbic acid at their cancer cytosol concentrations were shown to be capable of altering the metal speciation in the drug adduct with holo-transferrin but not that with albumin. The appearance of the additional peaks in ICP-MS electropherograms (by recording both Ru- and Fe-specific signals) was found to be dependent on time which allowed for kinetic assessment of the evolution of novel metal species. On the contrary, after the addition of citric acid the ruthenium ion (within the appropriately complexed scaffold) remained sequestered in the adduct. This was inferred as a proof of the speciation changes taking place by a virtue of a redox mechanism rather than due to ligand-exchange transformations. The protein-bound metallodrug was further characterized by direct ICP-MS assaying so as to confirm a partial release of ruthenium induced by glutathione.

  14. PoSSuM v.2.0: data update and a new function for investigating ligand analogs and target proteins of small-molecule drugs.

    Science.gov (United States)

    Ito, Jun-ichi; Ikeda, Kazuyoshi; Yamada, Kazunori; Mizuguchi, Kenji; Tomii, Kentaro

    2015-01-01

    PoSSuM (http://possum.cbrc.jp/PoSSuM/) is a database for detecting similar small-molecule binding sites on proteins. Since its initial release in 2011, PoSSuM has grown to provide information related to 49 million pairs of similar binding sites discovered among 5.5 million known and putative binding sites. This enlargement of the database is expected to enhance opportunities for biological and pharmaceutical applications, such as predictions of new functions and drug discovery. In this release, we have provided a new service named PoSSuM drug search (PoSSuMds) at http://possum.cbrc.jp/PoSSuM/drug_search/, in which we selected 194 approved drug compounds retrieved from ChEMBL, and detected their known binding pockets and pockets that are similar to them. Users can access and download all of the search results via a new web interface, which is useful for finding ligand analogs as well as potential target proteins. Furthermore, PoSSuMds enables users to explore the binding pocket universe within PoSSuM. Additionally, we have improved the web interface with new functions, including sortable tables and a viewer for visualizing and downloading superimposed pockets.

  15. Insights from investigating the interactions of adamantane-based drugs with the M2 proton channel from the H1N1 swine virus

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jing-Fang [College of Life Science and Biotechnology, Shanghai Jiaotong University, Shanghai 200240 (China); Wei, Dong-Qing, E-mail: dqwei@gordonlifescience.org [College of Life Science and Biotechnology, Shanghai Jiaotong University, Shanghai 200240 (China); Gordon Life Science Institute, 13784 Torrey Del Mar Drive, San Diego, CA 92130 (United States); Chou, Kuo-Chen [College of Life Science and Biotechnology, Shanghai Jiaotong University, Shanghai 200240 (China); Gordon Life Science Institute, 13784 Torrey Del Mar Drive, San Diego, CA 92130 (United States)

    2009-10-16

    The M2 proton channel is one of indispensable components for the influenza A virus that plays a vital role in its life cycle and hence is an important target for drug design against the virus. In view of this, the three-dimensional structure of the H1N1-M2 channel was developed based on the primary sequence taken from a patient recently infected by the H1N1 (swine flu) virus. With an explicit water-membrane environment, molecular docking studies were performed for amantadine and rimantadine, the two commercial drugs generally used to treat influenza A infection. It was found that their binding affinity to the H1N1-M2 channel is significantly lower than that to the H5N1-M2 channel, fully consistent with the recent report that the H1N1 swine virus was resistant to the two drugs. The findings and the relevant analysis reported here might provide useful structural insights for developing effective drugs against the new swine flu virus.

  16. 医院用药风险管理模式探讨%Investigation on Hospital Drug Use Risk Management Mode

    Institute of Scientific and Technical Information of China (English)

    李连新; 任昊芹

    2016-01-01

    Objective To improve the hospital's level in prevention,control and management of drug use risk. Methods Based on the theory of risk management for hospital,the potential risks were analyzed in order to prevent and control risks in hospital drug use. Results and Conclusion The risk management mode of hospital drug use,including risk identification,assessment,control,communi-cation and management evaluation,was established. Each link is an indispensable and important part of the drug use risk management system and should be strengthened and maintained. The links should be of good convergence,in order to effectively improve the level of hospital drug use risk management.%目的:提高医院防范、控制和管理用药风险的水平。方法依据风险管理理论分析医院可能存在的用药风险并提出应对策略,以充分加以预防和控制。结果与结论构建医院用药风险管理模式,包括风险的识别、评估、控制、沟通和管理评估5个环节,其中每个环节都是用药风险管理制度不可或缺的重要内容,应逐一加强监管并保持各环节间的良好衔接,以有效提高医院用药风险管理的水平。

  17. Against the investigation and analysis of the adverse reaction of tumor drugs%抗肿瘤药物不良反应调查与分析

    Institute of Scientific and Technical Information of China (English)

    郝朋朋; 李晓霞; 赵华; 牛业来

    2015-01-01

    Objective:Cancer drug adverse reaction through the clinical observation data analysis, for antitumor drug can cause adverse reactions are summarized.Methods:In our hospital between January 2007 and January 2009 application of antitumor drug adverse reaction caused by the 83 patients of report for statistical analysis.Results: Antitumor drug adverse reflect can appear in multiple systems, including in the digestive system.Conclusions:The clinical application of antitumor drug treatment of malignant tumor is easy to cause adverse reactions, clinical staff should pay attention to its adverse reactions, and as far as possible to reduce the occurrence of adverse reactions.%目的:通过临床观察对抗肿瘤药物的不良反应进行数据分析,为抗肿瘤药物可能引起的不良反应进行归纳。方法:对我院2007年1月至2009年1月应用抗肿瘤药物的83例病人产生的不良反应报告进行统计学分析。结果:通过数据分析得出,抗肿瘤药物的不良反映可以出现在多个系统,其中以消化系统最为突出。结论:临床上应用抗肿瘤药物治疗恶性肿瘤易引发不良反应,临床工作者应当重视其不良反应,并尽可能减少不良反应的发生。

  18. Factors affecting reoperations after anterior cervical discectomy and fusion within and outside of a Federal Drug Administration investigational device exemption cervical disc replacement trial.

    Science.gov (United States)

    Singh, Kern; Phillips, Frank M; Park, Dan K; Pelton, Miguel A; An, Howard S; Goldberg, Edward J

    2012-05-01

    The excellent clinical results of five US Federal Drug Administration (FDA) trials approved for cervical total disc replacement (TDR) (Prestige [Medtronic Sofamor Danek, Memphis, TN, USA], Bryan [Medtronic Sofamor Danek], ProDisc-C [Synthes, West Chester, PA, USA], Kineflex|C [SpinalMotion, Mountain View, CA, USA], and Mobi-C [LDR Spine, Austin, TX, USA]) have recently been published. In these prospective randomized studies, superiority or equivalency of TDR was claimed, citing an 8.7% (23/265), 9.5% (21/221), 8.5% (9/106), 12.2% (14/115), and 6.2% (5/81) (mean = 9.02%) rate of additional related cervical surgical procedures within 2 years in control anterior cervical discectomy and fusion (ACDF) patients, respectively, compared with 1.8% (5/276), 5.8% (14/242), 1.9% (2/103), 11% (15/136), and 1.2% (2/164) (mean = 4.34%) in patients receiving the cervical TDR. The rate of reoperation within 2 years after ACDF seems unusually high. To assess the rate of and specific indications for early reoperation after ACDF in a cohort of patients receiving the ACDF as part of their customary care. These results are contrasted with similar patients receiving ACDF as the control arm of five FDA investigational device exemption (IDE) studies. Multisurgeon retrospective clinical series from a single institution. One hundred seventy-six patients with spondylotic radiculopathy or myelopathy underwent ACDF by three surgeons between 2001 and 2005 as part of their clinical practices. All patients had at least 2 years of follow-up with final follow-up within 6 months of completion of this study. Cervical reoperation rates at 2-year follow-up and at 3.5-year follow-up. Review of medical records and telephone conversations were completed to determine the number of patients who had undergone a revision cervical procedure. At final follow-up, complete data were available for 159 ACDF patients. Of the 48 patients who underwent single-level ACDF and met criteria for inclusion in the IDE studies

  19. Investigation of Functionalized Poly(N,N-dimethylacrylamide)-block-polystyrene Nanoparticles As Novel Drug Delivery System to Overcome the Blood-Brain Barrier In Vitro.

    Science.gov (United States)

    Gregori, Maria; Bertani, Daniela; Cazzaniga, Emanuela; Orlando, Antonina; Mauri, Michele; Bianchi, Alberto; Re, Francesca; Sesana, Silvia; Minniti, Stefania; Francolini, Maura; Cagnotto, Alfredo; Salmona, Mario; Nardo, Luca; Salerno, Domenico; Mantegazza, Francesco; Masserini, Massimo; Simonutti, Roberto

    2015-12-01

    In the search of new drug delivery carriers for the brain, self-assembled nanoparticles (NP) were prepared from poly(N,N-dimethylacrylamide)-block-polystyrene polymer. NP displayed biocompatibility on cultured endothelial cells, macrophages and differentiated SH-SY5Y neuronal-like cells. The surface-functionalization of NP with a modified fragment of human Apolipoprotein E (mApoE) enhanced the uptake of NP by cultured human brain capillary endothelial cells, as assessed by confocal microscopy, and their permeability through a Transwell Blood Brain Barrier model made with the same cells, as assessed by fluorescence. Finally, mApoE-NP embedding doxorubicin displayed an enhanced release of drug at low pH, suggesting the potential use of these NP for the treatment of brain tumors.

  20. 常见口服药物最佳用法用量的探讨%Investigation of the optimal usage and dosage of common oral drugs

    Institute of Scientific and Technical Information of China (English)

    张项

    2014-01-01

    The oral medication therapy is the most common method of treatment in clinic,and it has advantages of sim-ple and quick delivery,reliable curative effect,no driect damage to skin and mucous membrane,and the relatively cheap price and so on,but the best usage and dosage of oral medication and the curative effect of drug are closely related.In order to better achieve the clinical effective and safe medicine,this paper discussed pharmaceutical dosage form,position and the time for taking medicine,takingmethods,taking solvent and exercise and so on influencing the curative effect of oral drugs,so that medical staff can better grasp the rational use of oral drugs, ans guide rational drug use of patients.%口服药物治疗是临床上最常见的一种治疗方法,具有给药简单快捷、疗效可靠、对皮肤和黏膜无直接损伤、价格相对便宜等优势,但口服药物的最佳用法用量与药物的疗效息息相关。为了更好地实现临床安全有效用药,本文就药物剂型、服药体位、服药时间、服药方式、服药溶剂和运动等因素对口服药物疗效的影响展开了探讨,以便于医护人员能够更好地正确掌握口服药物的合理使用,指导患者合理用药。

  1. Amphetamine and N-acetylamphetamine incorporation into hair: an investigation of the potential role of drug basicity in hair color bias.

    Science.gov (United States)

    Borges, C R; Wilkins, D G; Rollins, D E

    2001-01-01

    To elucidate the role of drug basicity in the preferential incorporation of certain drugs into dark hair rather than light hair, Long-Evans rats were dosed with amphetamine or its non-basic analogue N-acetylamphetamine (N-AcAp) and their hair evaluated for drug content. Rats were shaved prior to dosing. On the 14th day after dosing, hair from the same area that was shaved prior to dosing was shaved and collected. After the addition of amphetamine-d3 or N-AcAp-d3 as an internal standard, hair samples (20 mg) were digested in 1M NaOH at 37 degrees C. Digested solutions were then extracted with n-butyl chloride/chloroform (4:1, v/v). After drying and reconstituting, samples were injected onto a ThermoQuest TSQ liquid chromatography-tandem mass spectrometry instrument for analysis. Black hair from rats dosed with amphetamine (n = 8) was found to contain 6.44 +/- 1.31 (SD) ng amphetamine/mg hair. White hair from the same rats contained 2.04 +/- 0.58 ng amphetamine/mg hair. In contrast, no difference in N-AcAp content was found between black hair (0.87 +/- 0.08 ng N-AcAp/mg hair) and white hair (0.83 +/- 0.15 ng N-AcAp/mg hair) from rats dosed with N-AcAp (n = 8).

  2. 网上药品集中采购的方法探讨与应用%Investigation of Drug Centralized Purchase Online

    Institute of Scientific and Technical Information of China (English)

    邹晓华; 闵宏; 陈明洁

    2011-01-01

    Objective To perform drug centralized purchase through e-commerce network platform. Methods The computer network platform was used for centralized drug purchase online of the hospital. Results Centralized drug purchase online was practical, with the requirements of six national ministries. Conchiakn It's valuable to popularize the method of centralized procurement online that is scientific, standardized, secure, open and efficient. [Chinese Medical Equipment Journal, 2011,32(12) :53-55]%目的:利用电子商务网络平台进行药品集中采购.方法:应用计算机网络平台,对医院使用的所有招标药品实施网上集中采购.结果:网上药品集中采购切实可行,满足了国家六部委联合提出的医疗机构“网上药品集中采购”的要求.结论:网上药品集中采购具有科学、规范、安全、透明、快捷等优越性,值得广泛地推广应用.

  3. Drug Facts

    Medline Plus

    Full Text Available ... and Nicotine Facts Other Drugs of Abuse What is Addiction? What are some signs and symptoms of ... to Drugs? Does Addiction Run in Families? Why Is It So Hard to Quit Drugs? Effects of ...

  4. 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 ...

  5. Drug Resistance

    Science.gov (United States)

    HIV Treatment Drug Resistance (Last updated 3/2/2017; last reviewed 3/2/2017) Key Points As HIV multiplies in the ... the risk of drug resistance. What is HIV drug resistance? Once a person becomes infected with HIV, ...

  6. A Systematic Approach to Evaluate Herb-Drug Interaction Mechanisms: Investigation of Milk Thistle Extracts and Eight Isolated Constituents as CYP3A Inhibitors

    Science.gov (United States)

    Brantley, Scott J.; Graf, Tyler N.; Oberlies, Nicholas H.

    2013-01-01

    Despite increasing recognition of potential untoward interactions between herbal products and conventional medications, a standard system for prospective assessment of these interactions remains elusive. This information gap was addressed by evaluating the drug interaction liability of the model herbal product milk thistle (Silybum marianum) with the CYP3A probe substrate midazolam. The inhibitory effects of commercially available milk thistle extracts and isolated constituents on midazolam 1′-hydroxylation were screened using human liver and intestinal microsomes. Relative to vehicle, the extract silymarin and constituents silybin A, isosilybin A, isosilybin B, and silychristin at 100 μM demonstrated >50% inhibition of CYP3A activity with at least one microsomal preparation, prompting IC50 determination. The IC50s for isosilybin B and silychristin were ∼60 and 90 μM, respectively, whereas those for the remaining constituents were >100 μM. Extracts and constituents that contained the 1,4-dioxane moiety demonstrated a >1.5-fold shift in IC50 when tested as potential mechanism-based inhibitors. The semipurified extract, silibinin, and the two associated constituents (silybin A and silybin B) demonstrated mechanism-based inhibition of recombinant CYP3A4 (KI, ∼100 μM; kinact, ∼0.20 min−1) but not microsomal CYP3A activity. The maximum predicted increases in midazolam area under the curve using the static mechanistic equation and recombinant CYP3A4 data were 1.75-fold, which may necessitate clinical assessment. Evaluation of the interaction liability of single herbal product constituents, in addition to commercially available extracts, will enable elucidation of mechanisms underlying potential clinically significant herb-drug interactions. Application of this framework to other herbal products would permit predictions of herb-drug interactions and assist in prioritizing clinical evaluation. PMID:23801821

  7. The delayed luminescence spectroscopy as tool to investigate the cytotoxic effect on human cancer cells of drug-loaded nanostructured lipid carrier

    Science.gov (United States)

    Grasso, R.; Gulino, M.; Scordino, A.; Musumeci, F.; Campisi, A.; Bonfanti, R.; Carbone, C.; Puglisi, G.

    2016-05-01

    The first results concerning the possibility to use Delayed Luminescence spectroscopy to evaluate the in vitro induction of cytotoxic effects on human glioblastoma cells of nanostructured lipid carrier and drug-loaded nanostructured lipid carrier are showed in this contribution. We tested the effects of nanostructured lipid carrier, ferulic acid and ferulic acidloaded nanostructured lipid carrier on U-87MG cell line. The study seems to confirm the ability of Delayed Luminescence to be sensible indicator of alterations induced on functionality of the mitochondrial respiratory chain complex I in U-87MG cancer cells when treated with nanostructured lipid carriers.

  8. Marine steroids as potential anticancer drug candidates: In silico investigation in search of inhibitors of Bcl-2 and CDK-4/Cyclin D1.

    Science.gov (United States)

    Saikia, Surovi; Kolita, Bhaskor; Dutta, Partha P; Dutta, Deep J; Neipihoi; Nath, Shyamalendu; Bordoloi, Manobjyoti; Quan, Pham Minh; Thuy, Tran Thu; Phuong, Doan Lan; Long, Pham Quoc

    2015-10-01

    Star fishes (Asteroidea) are rich in polar steroids with diverse structural characteristics. The structural modifications of star fish steroids occur at 3β, 4β, 5α, 6α (or β), 7α (or β), 8, 15α (or β) and 16β positions of the steroidal nucleus and in the side chain. Widely found polar steroids in starfishes include polyhydroxysteroids, steroidal sulfates, glycosides, steroid oligoglycosides etc. Bioactivity of these steroids is less studied; only a few reports like antibacterial, cytotoxic activity etc. are available. In continuation of our search for bioactive molecules from natural sources, we undertook in silico screening of steroids from star fishes against Bcl-2 and CDK-4/Cyclin D1 - two important targets of progression and proliferation of cancer cells. We have screened 182 natural steroids from star fishes occurring in different parts of the world and their 282 soft-derivatives by in silico methods. Their physico-chemical properties, drug-likeliness, binding potential with the selected targets, ADMET (absorption, distribution, metabolism, toxicity) were predicted. Further, the results were compared with those of existing steroidal and non steroidal drugs and inhibitors of Bcl-2 and CDK-4/Cyclin D1. The results are promising and unveil that some of these steroids can be potent leads for cancer treatments.

  9. 多重耐药鲍曼不动杆菌感染情况调查及耐药分析%Investigation and Drug Resistance Analysis of Multi Drug Resistant Acineto-bacter Bauman Infection

    Institute of Scientific and Technical Information of China (English)

    李晓峰

    2016-01-01

    目的:分析当前鲍曼不动杆菌分布情况及其耐药性,为今后医院的感染防治及临床医疗改进工作提供充足的依据。方法回顾性分析该院在2012年1月—2013年1月(A组)及2013年6月—2015年6月(B组)两个时间段内各200株鲍曼不动杆菌的感染情况和耐药性特点。结果于2013年实行全新的医院临床护理制度之后,鲍曼不动杆菌检出率明显降低,由之前的45%下降到7%;同时鲍曼不动杆菌对于常见抗菌药物的敏感性与之前相比明显提高;鲍曼不动杆菌于呼吸科和重症监护室的检出率最高,分别为77.89%和44.23%(P<0.05)。结论鲍曼不动杆菌耐药性高,常见于呼吸道疾病和重症疾病。为有效降低鲍曼不动杆菌的感染率,提高对抗菌药物的敏感性,建议不断改善临床护理能力和水平,提高护理操作的准确度,降低病菌的感染率。%Objective To analyze the distribution of Acinetobacter Bauman and analyze its drug resistance, and to provide sufficient evidence for the prevention and treatment of hospital infection and the improvement of clinical medicine. Meth-ods The infection status and drug resistance of 200 strains of Bauman Acinetobacter were retrospectively analyzed in a hos-pital from January 2012 to January (-2013 group) and June-2015 (B group) in two time periods of A. Results in 2013 to implement new hospital clinical nursing system, Acinetobacter baumannii detection rate was significantly lower, 45% from the previous fall to 7%; and Acinetobacter baumannii to common antibacterial drug sensitivity was higher than that of;Acinetobacter baumannii in respiratory department and intensive care unit of the highest detection rate, respectively 77.89%and 44.23%(P< 0.05). Conclusion Acinetobacter baumannii coli resistance is high, is common in severe diseases and res-piratory diseases. In order to effectively reduce the Acinetobacter bacillus infection rate and improve the

  10. Investigation on the Present Situation of Food and Drug Inspection Resources in Guangxi Food and Drug System%广西食药监系统食品药品检验检测资源现状调查

    Institute of Scientific and Technical Information of China (English)

    谌晓勤; 吴维民; 曾立威; 蒋帅; 霍海英; 李艺钊; 黄苑清

    2015-01-01

    Objective: To have an overall view of the present situation of food and drug inspection resources in Guangxi food and drug administration system, so as to improve the detection of resources, enhance the inspection ability, and play a better security role in proposed technical support.Methods:The self-made questionnaire was carried out by the Guangxi provincial food and drug administration, and the data were collected online direct network reporting. Results:The results showed that most of the inspection personnel had received college education, and majority of them had the primary job titles or below; most of the finance was invested by the central government and the provincial government, accounting for 36.49%, and 42.31% respectively; the equipment distribution was extremely uneven, the provincial inspection agencies had 50.11% of the instrument and equipment; institutional research capacity of municipal detection organization was much lower than provincial agencies.Conclusion:It is necessary to appropriately increase the preparation, improve the education and job title of inspection personnel, It is necessary to strengthen the city and county levels of government agencies for the detection of ifnancial investment, It is necessary to enhance the city and county agencies to detect equipment investment and it is necessary to put emphasis on institutional capacity building inspection.%目的:了解广西食药监系统食品药品检验检测资源现状,为改善检测资源、提升检验能力,更好地发挥检测机构的技术保障作用提出建议。方法:自制问卷,通过广西食品药品监督管理局下发问卷,采用网络直报的方式收集数据。结果:调查显示:检验人员学历以本科为主,职称以初级及以下职称为主;财政投入以中央财政和区政府为主,分别占36.49%、42.31%;仪器设备分布极不均衡,区级检测机构拥有50.11%不同价值的仪器设备;市级检测机构科

  11. Pharmacology and drug distribution

    Energy Technology Data Exchange (ETDEWEB)

    Morgan, L.R.; Weatherall, T.J.

    1979-08-01

    An overview of the pharmacology of drugs in the treatment of cancer is presented. The discussion begins with the simplest relationship of drugs and particles to one another then proceeds to demonstrate the interrelationship in a biologic system to produce a chemobiodynamic response. The basic principles of pharmacokinetics are reviewed and their correlation with investigational and standard drug therapies is discussed. Voids in the consideration of interactions between chemotherapy and radiotherapy are discussed.

  12. Investigation and Evaluation of International Rational Drug Use Index in a Hospital%某医院门诊合理用药国际指标调查与评价

    Institute of Scientific and Technical Information of China (English)

    李素华; 杨悦; 李姗

    2011-01-01

    OBJECTIVE: To investigate and review prescription drug use in the outpatient department of a hospital, and to promote rational drug use. METHODS: 8 009 outpatient prescriptions and 360 on-spot questionnaires among patients were conducted in a certain hospital in July, September and November in 2009 of 28 departments. Compared with WHO standard, the data of rational drug use was analyzed statistically to evaluate rational drug use index. RESULTS: Prescription index: 2.26 kinds of drugs were used in each prescription averagely; generic name of drugs accounted for 90.38%; antibiotics, injections and essential drugs accounted for 30.18%, 22.30%, and 54.96%, respectively; the average amount of drugs was 216.16 yuan. Patient care index: average visiting time was 7.72 min and average explanatory time was 30 secs; the percentage of drug dispensing was 100%; 100% drugs were labeled; the percentage of patients, who understood the drugs usage, accounted for 95.36%. CONCLUSION: Results of survey show that the outpatient-prescriptions from the hospital have met medication standard in the following aspects: the average number of drugs in each prescription; the percentage of generic name of drugs; the percentage of antibiotics use; average visiting time; the percentage of the factual drug dispensing; the percentage of the complete drugs label; correct drug use methods being familiar with patients. However, it still needs improvement in following aspects: the percentages of injections and essential drugs, average explanatory time. The survey has pointed out the factors which influence the rational drug use in the hospital and provided evidence for further pragmatic intervention measures in use of injections and essential drugs and the average explanatory time.%目的:对某医院门诊科室的处方用药状况进行调查和点评,提高其合理用药水平.方法:抽取某医院2009年7、9、11月28个科室的门诊处方共8009张,

  13. 天津市北辰家蝇抗药性调查%Investigation on resistance to drugs of musca domestica in Beichen District of Tianjin

    Institute of Scientific and Technical Information of China (English)

    王淑惠; 张静; 孟庆贺

    2012-01-01

    Objective To understand the resistance to drugs of musca domestica in Beichen District of Tianjin, and instruct people to use insecticides properly. Method Determine the median lethal dose (LD50) of musca domestica by dropping method. Results The LD50 values of musca domestica against 5 common insecticides of DDVP, beta - cypermethrin, deltamethrin, propoxur and permethrin were 0. 0 530, 0. 0 310, 0.0 217, 0. 1 902 and 0. 0 262 μg per musca domestica, respectively. Compared with sensitive insects, the R/S values of DDVP was 10. 0 times, beta - cypermethrin was 50. 82 times, deltamethrin was 22. 85 times, propoxur was 3. 30 times and permethrin was 2. 34 times. Conclusions The musca domestica in Beichen District had different resistances against the 5 common insecticides, of which, beta - cypermethrin and deltamethrin had the most significant effect We suggested to strengthen the monitoring of resistance to drugs, use insecticides properly, and adopt comprehensive control strategies so as to reduce the development of resistance to drugs.%目的 了解天津北辰区家蝇抗药性情况,指导合理使用杀虫剂.方法 用点滴法测定家蝇半数致死量(LD50).结果 北辰区家蝇对5种常用杀虫剂的LD50依次为敌敌畏0.0 530μg/只、高效氯氰菊酯0.0 310μg/只、溴氰菊酯0.0217μg/只、残杀威0.1902μg/只、氯菊酯0.0 262μg/只.与敏感试虫相比,R/S值敌敌畏为10.0倍、高效氯氰菊酯为50.82倍、溴氰菊酯为22.85倍、残杀威为3.30倍、氯菊酯为2.34倍.结论 北辰区野外家蝇对5种常见杀虫剂均产生不同程度的抗药性,以高效氯氰菊酯和溴氰菊酯最为著.建议加强抗药性监测,科学合理用药,采取综合防治措施,减缓抗药性的发展.

  14. 转基因技术在疟原虫药物抗性机制研究中的应用%Investigation of drug-resistant mechanism of malaria parasites by transfection technology

    Institute of Scientific and Technical Information of China (English)

    叶润; 张冬梅; 潘卫庆

    2010-01-01

    疟疾是世界上危害人类健康最严重的感染性疾病之一.随着抗疟药物的广泛使用,疟原虫抗药性问题日趋严重.开展疟原虫药物抗性机制的研究,有助于开发新的药物以及制定用药策略.采用疟原虫转基因的方法能够从分子水平证实抗性基因与药物敏感的相关性以及基因突变在药物抗性产生中所起的作用.该文综述了疟原虫转基因技术在氯喹和磺胺多辛-乙胺嘧啶药物抗性机制研究中的应用.%Malaria is one of the leading infectious diseases in the world. The acquisition and spread of drug-resistant parasite arose gradually since widely utilization of antimalarial drugs. Investigations of the drugresistant mechanisms of malaria parasites may have advantages in developing new drug and modifying chemotherapy strategy. Introduction of transfection technologies made it possible to prove the role of candidate genes responsible for drug resistance, and the contribution of specific mutations to the resistance phenotype. This review focused on the application of transfection technologies in both Plasmodium falciparum and P. vivax to dissect the mechanisms of antimalarial drug resistance including chloroquine and sulfadoxin-pyrimethamine.

  15. Psychological status of the drug abusers under mandatory quarantine treatment: Investigation and analysis on 752 cases%752例强制隔离戒毒者心理健康状况的多层次比较

    Institute of Scientific and Technical Information of China (English)

    韦克诚; 何苗苗; 刘涛; 杨玉祥; 刘新民; 金明琦; 张婷; 滕永升; 周黎红; 徐东彪; 李桦

    2012-01-01

    目的:了解戒毒者心理健康状况,为强制隔离戒毒模式的心理康复提供依据.方法:对752例戒毒者采用90项症状清单(SCL-90)进行测验,并进行心理健康的多层次比较.结果:戒毒人员的各项评分均高于全国常模,差异非常显著(P<0.001),不同类型的戒毒人员测验结果有差异.结论:强制隔离戒毒人员存在严重的心理健康问题,不同类型的戒毒人员心理健康状况不同,应采取个体化的和有效的心理干预措施.%Objective:To investigate the psychological status of substance users for providing evidences for psychological rehabilitation of this population undergoing enforced isolated detoxification treatment.Methods-.The Symptom Checklist-90 ( SCL-90 ) was used to evaluate the psychological status in 752 drug users and the results were compared in different levels. Results :The drug abstainers scored averagely higher on each item as compared with national norm, with significant statistical difference( P < 0.001 ),and the differences were seen in different types of drug users. Conclusion: Serious psychological disorders exist in the drug abstainers under the mandatory quarantine treatment, and different types of drug abusers have exhibited diverse psychological status, which suggests that individualized treatment should be important to the effective psychologicalintervention of this population.

  16. Development of a novel in-vivo drug/in-vitro light system to investigate mechanisms of cell killing with photodynamic therapy

    Science.gov (United States)

    Hampton, James A.; Selman, Steven H.

    1991-06-01

    Over the last decade considerable interest has developed in the use of exogenously administered chromophores in combination with visible light for the treatment of human tumors. Whether cells are killed directly, or indirectly as a result of disruption of the tissue, microvasculature is unknown. The authors have developed methods to assess in short term culture the effects of PDT on precision cut tissue slices. The use of these tissue slices provide an important link between in vivo studies and in vitro isolated cultured cells for the following reasons: 1) slices contain all of the normal cells in their proper in vivo architectural arrangement; 2) since slices can be obtained relatively easily and in a very short period of time (a few minutes), animals can be treated with compounds in vivo, the tissue can be removed, sliced and mechanistic studies performed in vitro (without the several hours delay required to produce cultured cells); 3) in vitro comparisons between species, including human, can be readily made; and 4) mechanisms of PDT-induced cell killing can be studied in the absence of a functioning vascular system. Using this in vivo drug/in vitro light system, the results presented will detail the findings using normal rat liver and a transplantable rat tumor model.

  17. FT-Raman, FT-IR and UV-visible spectral investigations and ab initio computations of anti-epileptic drug: vigabatrin.

    Science.gov (United States)

    Edwin, Bismi; Joe, I Hubert

    2013-10-01

    Vibrational analysis of anti-epileptic drug vigabatrin, a structural GABA analog was carried out using NIR FT-Raman and FTIR spectroscopic techniques. The equilibrium geometry, various bonding features and harmonic vibrational wavenumbers were studied using density functional theory method. The detailed interpretation of the vibrational spectra has been carried out with the aid of VEDA.4 program. Vibrational spectra, natural bond orbital analysis and optimized molecular structure show clear evidence for the effect of electron charge transfer on the activity of the molecule. Predicted electronic absorption spectrum from TD-DFT calculation has been compared with the UV-vis spectrum. The Mulliken population analysis on atomic charges and the HOMO-LUMO energy were also calculated. Good consistency is found between the calculated results and experimental data for the electronic absorption as well as IR and Raman spectra. The blue-shifting of the C-C stretching wavenumber reveals that the vinyl group is actively involved in the conjugation path. The NBO analysis confirms the occurrence of intramolecular hyperconjugative interactions resulting in ICT causing stabilization of the system. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. Investigations into the stabilisation of drugs by sugar glasses : II: Delivery of an inulin-stabilised alkaline phosphatase in the intestinal lumen via the oral route

    NARCIS (Netherlands)

    Eriksson, H.J.C.; Verweij, W.R.; Poelstra, K.; Hinrichs, W.L.J.; de Jong, G.J.; Somsen, G.W.; Frijlink, H.W.

    2003-01-01

    In this study the possibility to deliver the acid-sensitive enzyme alkaline phosphatase (AP) from calf intestine (CIAP) to the intestinal system by oral administration was investigated. Tablets were prepared and in vitro evaluated. Final proof of concept studies were performed in rats. This acid lab

  19. [Investigation of Predisposition Biomarkers to Identify Risk Factors for Drug-induced Liver Injury in Humans: Analyses of Endogenous Metabolites in an Animal Model Mimicking Human Responders to APAP-induced Hepatotoxicity].

    Science.gov (United States)

    Kobayashi, Akio; Kondo, Kazuma; Sugai, Shoichiro

    2015-01-01

    Drug-induced liver injury is a main reason of regulatory action pertaining to drugs, including restrictions to clinical indications and withdrawal from the marketplace. Acetaminophen (APAP) is a commonly used and effective analgesic/antipyretic agent and relatively safe drug even in long-term treatment. However, it is known that APAP at therapeutic doses may cause hepatotoxicity in some individuals. Hence great efforts have been made to identify risk factors for APAP-induced chronic hepatotoxicity. We investigated the contribution of undernourishment to susceptibility to APAP-induced chronic hepatotoxicity using an animal model. We employed daytime restricted fed (RF) rats as a modified-nutritional state model for human APAP-induced hepatotoxicity. RF and ad libitum fed (ALF) rats were given APAP at 0, 300, and 500 mg/kg for 3 months. Plasma and urinary glutathione-related metabolomes and liver function parameters were measured during the dosing period. Endogenous metabolites forming at different levels between the RF and ALF rats could be potential predisposition biomarkers for APAP-induced hepatotoxicity. In addition, RF rats were considered a useful model to estimate the contribution of nutritional state of patients to APAP-induced chronic hepatotoxicity. In this article we report our current research focusing on nutritional state as risk factor for APAP-induced chronic hepatotoxicity and our findings of hepatotoxicity biomarkers.

  20. Investigation of common pathogenic bacteria and drug resistance in gerontism with bronchieetasis concurrent infection.%老年支气管扩张合并感染的常见病原菌及其耐药性调查

    Institute of Scientific and Technical Information of China (English)

    许立; 张锡林

    2011-01-01

    目的 调查分析老年支气管扩张合并感染的常见病原菌及其耐药情况,为临床合理应用抗菌药物提供依据.方法 对189例老年支气管扩张合并感染的住院患者的痰培养和药敏结果进行回顾性调查分析.结果 189例患者病原菌检测阳性122例,阳性率为64.6%,病原菌以革兰阴性杆菌为和真菌为主,分别占59.5%和10.8%;主要致病的革兰阴性杆菌对头孢呋辛、氨苄西林等药物耐药率高,对β-内酰胺类、碳青酶烯类、氨基糖甙类和喹诺酮类药物的耐药率相对较低.结论 老年支气管扩张合并感染病原菌以革兰阴性杆菌和真菌为主要条件致病菌,主要致病菌耐药率高,建议在药敏指导下用药.在未取得细菌药敏结果前可根据其病原菌分布特点经验性选择抗生素,宜采用联合抗菌药物治疗.%To investigate common pathogenic bacteria and drug resistance m gerontism with bronchiectasis concurrent infection, to make reasonable use of antibacterials. Methods Retrospectively analyzed sputum culture and drug sensitivity of 189 old patients with bronchiectasis concurrent infection. Results 122 people had masculine pathogenic bacteria, the masculine rate was 64.6%, then the rate of gram negative bacilli (GNB) was 59.5%, fungus was 10.8%; the drug resistance rate of GNB to Cefuroxime and Ampicillin was high, but to β-lactam antibiotics, carbapenem antibiotics, aminoglycosides and quinolones was low. Conclusion The main pathogenic bacteria in gerontism with bronchiectasis concurrent infection was gram negative bacilli and fungus, the rate of drug resistance was high, used antibiotics on the basis of drug sensitivity, selected antibiotics on the basis of the disposition feature of pathogenic bacteria, there was the best to use combination antibacterial drug therapy.

  1. An investigation into the interactions of gold nanoparticles and anti-arthritic drugs with macrophages, and their reactivity towards thioredoxin reductase

    Energy Technology Data Exchange (ETDEWEB)

    James, Lloyd R.A.; Xu, Zhi-Qiang; Sluyter, Ronald; Hawksworth, Emma L.; Kelso, Celine; Lai, Barry; Paterson, David J.; de Jonge, Martin D.; Dixon, Nicholas E.; Beck, Jennnifer L.; Ralph, Stephen F.; Dillon, Carolyn T.

    2014-01-01

    Gold(I) complexes are an important tool in the arsenal of established approaches for treating rheumatoid arthritis (RA), while some recent studies have suggested that gold nanoparticles (Au NPs) may also be therapeutically efficacious. These observations prompted the current biological studies involving gold(I) anti-RA agents and Au NPs, which are aimed towards improving our knowledge of how they work. The cytotoxicity of auranofin, aurothiomalate, aurothiosulfate and Au NPs towards RAW264.7 macrophages was evaluated using the MTT assay, with the former compound proving to be the most toxic. The extent of cellular uptake of the various gold agents was determined using graphite furnace atomic absorption spectrometry, while their distribution within macrophages was examined using microprobe synchrotron radiation X-ray fluorescence spectroscopy. The latter technique showed accumulation of gold in discrete regions of the cell, and co-localisation with sulfur in the case of cells treated with aurothiomalate or auranofin. Electrospray ionization mass spectrometry was used to characterize thioredoxin reductase (TrxR) in which the penultimate selenocysteine residue was replaced by cysteine. Mass spectra of solutions of TrxR and aurothiomalate, aurothiosulfate or auranofin showed complexes containing bare gold atoms bound to the protein, or protein adducts containing gold atoms retaining some of their initial ligands. These results support TrxR being an important target of gold(I) drugs used to treat RA, while the finding that Au NPs are incorporated into macrophages, but elicit little toxicity, indicates further exploration of their potential for treatment of RA is warranted.

  2. Toxicological investigation of forensic cases related to the designer drug 3,4-methylenedioxypyrovalerone (MDPV): Detection, quantification and studies on human metabolism by GC-MS.

    Science.gov (United States)

    Grapp, Marcel; Kaufmann, Christoph; Ebbecke, Martin

    2017-02-02

    3,4-methylenedioxypyrovalerone (MDPV) is a synthetic cathinone belonging to the class of α-pyrrolidinophenones that become increasingly popular as a designer psychostimulant. Here, we report a comprehensive collection of MDPV exposure with quantitative serum level confirmation in Germany. During the years 2014-2016, we could proof consumption of MDPV in 23 cases where urine and blood samples were submitted to our laboratory by the police of Lower Saxony. Most of the samples underwent systematic toxicological analysis by gas chromatography-mass spectrometry (GC-MS), where MDPV could be detected in urine and/or serum samples. The determined concentrations of MDPV in serum showed a high variability, ranging from traces (<10ng/mL) up to 576ng/mL with a mean concentration of 118ng/mL and median of 47ng/mL. The majority of MDPV users were men (87%) and the age ranged from 23 to 49 years (mean 35.9, median 37 years). For most of the analytically confirmed MDPV cases we could prove co-consumption of other psychotropic drugs with frequent occurrence of opiates and cannabinoids in 22% of the cases, followed by benzodiazepines and cocaine in 17%. Analysis of urine samples by GC-MS disclosed the presence of MDPV and its metabolites 2'-oxo-MDPV, demethylenyl-MDPV, demethylenyl-methyl-MDPV, demethylenyl-oxo-MDPV, demethylenyl-methyl-oxo-MDPV and demethylenyl-methyl-N,N-bisdealkyl-MDPV. The metabolite pattern substantiates previous suggestions for principle metabolic pathways of MDPV in humans.

  3. Investigation on the Electrocatalytic Determination and Photocatalytic Degradation of Neurotoxicity Drug Clioquinol by Sn(MoO4)2 Nanoplates.

    Science.gov (United States)

    Karthik, Raj; Vinoth Kumar, Jeyaraj; Chen, Shen-Ming; Seerangan, Kumar; Karuppiah, Chelladurai; Chen, Tse-Wei; Muthuraj, Velluchamy

    2017-08-09

    Transition-metal molybdates have concerned enormous curiosity as supercapacitors, photocatalysts, and electrocatalysts. These materials are the best alternatives to noble-metal-based catalysts, which are generally show a limited photocatalytic and electrocatalytic activity. In addition, the antiprotozoal drug can usually pollute the environment through improper disposable and incomplete metabolism, and it is very dangerous to humans as well as aquatic animals. Therefore, here, we have studied the electrochemical determination and photodegradation of neurotoxicity clioquinol (CQL) by nanoplate-like tin molybdate (Sn(MoO4)2, denoted as SnM), which is used as both an electro- and a photocatalyst. The as-prepared catalyst delivered a highly efficient activity toward the detection and degradation of CQL. The proposed nanoplate-like SnM was prepared through a simple wet-chemical route, and its physicochemical properties were characterized by various spectroscopic and analytical techniques. As an electrochemical sensor, the SnM electrocatalyst exhibited tremendous activity for the detection of CQL in terms of lower potential and enhanced anodic peak current. In addition, it showed high selectivity, a wide linear concentration range, a lower detection limit, and good sensitivity. From the UV-vis spectroscopy study, the SnM photocatalyst delivered an excellent photocatalytic activity toward the degradation of CQL in terms of increasing contact time and reducing CQL concentration, resulting in the increasing of the degradation efficiency about 98% within 70 min under visible light irradiation and showing an appreciable stability by observation of the reusability of the catalyst.

  4. NMR investigations of structural and dynamics features of natively unstructured drug peptide - salmon calcitonin: implication to rational design of potent sCT analogs.

    Science.gov (United States)

    Rawat, Atul; Kumar, Dinesh

    2013-01-01

    Backbone dynamics and conformational properties of drug peptide salmon calcitonin have been studied in aqueous solution using nuclear magnetic resonance (NMR). Although salmon calcitonin (sCT) is largely unfolded in solution (as has been reported in several circular dichroism studies), the secondary H(α) chemical shifts and three bond H(N) -H(α) coupling constants indicated that most of the residues of the peptide are populating the α-helical region of the Ramachandran (ϕ, ψ) map. Further, the peptide in solution has been found to exhibit multiple conformational states exchanging slowly on the NMR timescale (10(2) -10(3)  s(-1) ), inferred by the multiple chemical shift assignments in the region Leu4-Leu12 and around Pro23 (for residues Gln20-Tyr22 and Arg24). Possibly, these slowly exchanging multiple conformational states might inhibit symmetric self-association of the peptide and, in part, may account for its reduced aggregation propensity compared with human calcitonin (which lacks this property). The (15) N NMR-relaxation data revealed (i) the presence of slow (microsecond-to-millisecond) timescale dynamics in the N-terminal region (Cys1-Ser5) and core residues His17 and Asn26 and (ii) the presence of high frequency (nanosecond-to-picosecond) motions in the C-terminal arm. Put together, the various results suggested that (i) the flexible C-terminal of sCT (from Thr25-Thr31) is involved in identification of specific target receptors, (ii) whereas the N-terminal of sCT (from Cys1-Gln20) in solution - exhibiting significant amount of conformational plasticity and strong bias towards biologically active α-helical structure - facilitates favorable conformational adaptations while interacting with the intermembrane domains of these target receptors. Thus, we believe that the structural and dynamics features of sCT presented here will be useful guiding attributes for the rational design of biologically active sCT analogs.

  5. Change in enrollment patterns, patient selection, and clinical outcomes with the availability of drug-eluting stents in the Bypass Angioplasty Revascularization Investigation 2 Diabetes trial

    Science.gov (United States)

    Shah, Binita; Srinivas, Vankeepuram S.; Lu, Jiang; Brooks, Maria M.; Bates, Eric R.; Nedeljkovic, Zoran S.; Escobedo, Jorge; Das, Gladwin S.; Lopez, John J.; Feit, Frederick

    2013-01-01

    Background In the BARI 2D trial, patients with type 2 diabetes and stable coronary artery disease were randomized to prompt revascularization versus intensive medical therapy (IMT). This analysis sought to evaluate how the availability of drug-eluting stents (DESs) has changed practice and outcomes. Methods In BARI 2D, 1,605 patients were in the percutaneous coronary intervention (PCI)–intended stratum. As DES became available midway through recruitment, we report clinical outcomes among patients who underwent IMT versus prompt PCI with bare-metal stents (BMSs) or DES up to 4 years. Results In North America, after DES became available, selection for the PCI-intended stratum increased from 73% to 79% (P = .003). Fewer BMS than DES patients had total occlusions treated or underwent rotational atherectomy (5.6% vs 9.7%, P = .02, and 1.2% vs 3.7%, P < .01, respectively). Subsequent revascularization (IMT 39%, BMS 29%, DES 21%, P < .01) and target vessel revascularization (BMS 16.1% vs DES 9.6%, P = .03) were lower with DES. Angina at 2 years tended to be less common with DES (IMT 39%, BMS 37%, DES 29%, P = .04, for 3 groups, P = .07 for DES vs BMS). The composite of death, myocardial infarction, or stroke was IMT 16.0%, BMS 20.5%, DES 17.5%; P = .80. Conclusions When DES became available in North America, patients were more likely to be selected into the PCI-intended stratum. Compared with patients receiving BMS, those receiving DES tended to have less target vessel revascularization and angina. PMID:24016502

  6. 2014年某院儿科门诊处方超说明书用药情况调查%Investigation of Off-label Drug Use in Pediatric Outpatient Department of Hospital in 2014

    Institute of Scientific and Technical Information of China (English)

    刘姗娟

    2016-01-01

    OBJECTIVE:To investigate the off-label drug use conditions in pediatric outpatient department of Jingzhou Maternal and Child Health Hospital ( hereinafter referred to as "our hospital") , and to provide reference for the ration drug use in children .METHODS:Prescriptions from pediatric outpatient department of our hospital in 2014 were randomly selected,to judge the medical orders by the drug instruction ,and statistical analysis was conducted on the incidence and types of off-label drug use ,incidence of off-label drug use in children at different age stages and the drugs categories , etc.RESULTS:Of the 1 200 sampled prescriptions , 3 258 cases involved in medical orders , the incidence rate of off-label drug use were 43.83%.The top 3 types of off-label drug use were respectively over optimal application groups ( 53.81%) , over times of administration ( 20.30%) , over dosage of administration ( 13.20%) . Infancy(45.26%),toddler age (45.15%)and preschool age (44.03%)dominated the top 3 places.Meanwhile,the top 3 drugs of off-label drug use were microbe and mineral drugs (55.87%),Chinese patent medicine (50.29%)and anti-infectious agents (46.40%) .CONCLUSIONS:Off-label drug use is a widely existing phenomena ,which needs the clinical physicians to have a good knowledge of drug introductions , and to carry out off-label drug use only with the permission of the patients 'parents;at the same time, the Health Administration should formulate the related management system on off-label drug use ,so as to ensure the safe and effective medication in children .%目的:了解荆州市妇幼保健院(以下简称"我院")儿科门诊超说明书用药现状,为促进儿童安全合理用药提供参考.方法:随机抽取我院2014年门诊儿科处方,根据药品说明书判断医嘱是否超说明书用药,对超说明书用药发生率、超说明书用药类型、各年龄段儿童超说明书用药发生率及药品种类等进行统计分析.结果:在抽取的1 200张

  7. Investigation and Analysis of Commonly Used Solvent for Resolvation of Antitumor Drug for Injection%常用注射用抗肿瘤药物复配溶媒的调查与分析

    Institute of Scientific and Technical Information of China (English)

    荣晨; 李建涛; 李鹏; 张凡; 张翠莲

    2014-01-01

    The use of antitumor drug is one of the main means to treat cancer at present. Clinically the medicines are mainly administered by injection. The antitumor drug for injection need to use an appropriate solvent and dosage for resolvation,so as to ensure the stability and safety during the stage of transfusion and clinical treatment. In this paper through retrieval of Micromedex and China Hospital Knowledge Database (CHKD),an investigation was made on the selection of 42 kinds (56 specifications) of solvents which were commonly used in our hospital for antitumor drug for injection,and analysis was made based on drug package inserts. A reference was thus provided for rapid review of prescription by clinical pharmacist.%抗肿瘤药物是目前治疗肿瘤的主要手段之一,临床上多以注射给药为主。而注射用抗肿瘤药物的复配需要选择适宜的溶媒与用量,以保证输注期间药品的稳定性及临床用药的安全性。本文主要以药品说明书为依据,通过检索Micromedex和中国医院知识总库(CHKD),对我院临床常用42种(56个品规)注射用抗肿瘤药物的溶媒选择进行调查、汇总与分析,为临床药师快速审方提供参考。

  8. Investigating the enteroenteric recirculation of apixaban, a factor Xa inhibitor: administration of activated charcoal to bile duct-cannulated rats and dogs receiving an intravenous dose and use of drug transporter knockout rats.

    Science.gov (United States)

    Zhang, Donglu; Frost, Charles E; He, Kan; Rodrigues, A David; Wang, Xiaoli; Wang, Lifei; Goosen, Theunis C; Humphreys, W Griffith

    2013-04-01

    The study described here investigated the impact of intestinal excretion (IE; excretion of drug directly from circulation to intestinal lumen), enteroenteric recirculation (EER), and renal tubule recirculation (RTR) on apixaban pharmacokinetics and disposition. The experimental approaches involve integrating apixaban elimination pathways with pharmacokinetic profiles obtained from bile duct-cannulated (BDC) rats and dogs receiving i.v. doses together with oral administration of activated charcoal (AC). Additionally, the role of P-gp (P-glycoprotein; abcb1) and BCRP (breast cancer resistance protein; abcg2) in apixaban disposition was evaluated in experiments using transporter inhibitors and transporter knockout (KO) rats. Approximately 20-50% of an apixaban i.v. dose was found in feces of BDC rats and dogs, suggesting IE leading to fecal elimination and intestinal clearance (IC). The fecal elimination, IC, and systemic clearance of apixaban were increased upon AC administration in both BDC rats and dogs and were decreased in BDC rats dosed with GF-120918, a dual BCRP and P-gp inhibitor). BCRP appeared to play a more important role for absorption and intestinal and renal elimination of apixaban than P-gp in transporter-KO rats after oral and i.v. dosing, which led to a higher level of active renal excretion in rat than other species. These data demonstrate that apixaban undergoes IE, EER, and RTR that are facilitated by efflux transporters. Intestinal reabsorption of apixaban could be interrupted by AC even at 3 hours post-drug dose in dogs (late charcoal effect). This study demonstrates that the intestine is an organ for direct clearance and redistribution of apixaban. The IE, EER, and RTR contribute to overall pharmacokinetic profiles of apixaban. IE as a clearance pathway, balanced with metabolism and renal excretion, helps decrease the impacts of intrinsic (renal or hepatic impairment) and extrinsic (drug-drug interactions) factors on apixaban disposition.

  9. Drug Facts

    Medline Plus

    Full Text Available ... Marijuana (Weed, Pot) Facts MDMA (Ecstasy, Molly) Facts Meth (Crank, Ice) Facts Pain Medicine (Oxy, Vike) Facts ... Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine Other Drugs ...

  10. Drugged Driving

    Science.gov (United States)

    ... Parents & Educators Children & Teens Search Connect with NIDA : Google Plus Facebook LinkedIn Twitter YouTube Flickr RSS Menu ... misuse of prescription drugs can make driving a car unsafe—just like driving after drinking alcohol. Drugged ...

  11. Drug Facts

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    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 ...

  12. Drug Facts

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    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 ...

  13. Drug Facts

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    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. Study Drugs

    Science.gov (United States)

    ... study drugs: amphetamines like Adderall, Dexedrine, or Vyvanse methylphenidates like Ritalin or Concerta Most people get study ... How Much Sleep Do I Need? Prescription Drug Abuse How to Make Homework Less Work Organizing Schoolwork & ...

  15. Drug Facts

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    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 ...

  16. Drug Facts

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    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 ...

  17. Drugs (image)

    Science.gov (United States)

    ... Drugs for fever, cough, stuffy nose, runny nose, diarrhea, and allergies are common drugs which are especially helpful during times of illness. All medications should be kept out of the reach of children.

  18. Drug Facts

    Science.gov (United States)

    ... drug. "Max" was addicted to prescription drugs. The addiction slowly took over his life. I need different people around me. To stop using marijuana, "Cristina" is making positive changes in her life. She finds support from ...

  19. Drug Facts

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    Full Text Available ... Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine Other Drugs You can call 1-800-662-HELP (4357) at any time to find drug treatment centers near you. I want my daughter to ...

  20. 预防用药在化疗所致不良反应中的作用调查分析%Investigation and Analysis of the Effect of Preventive Medication on Adverse Drug Reactions due to Chemotherapy

    Institute of Scientific and Technical Information of China (English)

    张霞; 谢嵩

    2011-01-01

    目的 探讨预防用药在化疗所致不良反应中的作用,为临床合理应用抗肿瘤药物、提高患者生存质量提供参考.方法 选择我院恶性肿瘤患者306例,调查分析预防用药的作用,探索其规律性.结果与结论 预防用药可以减少化疗时引起的不良反应,5-羟色胺类药物对减少化疗引起的胃肠道不良反应有很大作用,基因重组人粒细胞集落刺激因子对化疗所致骨髓抑制有良好的预防和治疗作用.合理使用预防药物可以保障化疗的顺利进行,提高患者对化疗的耐受性及生存质量.%OBJECTIVE: To investigate the pathological data of the tumor patients and analyze the effect of preventive medication on adverse drug reactions (ADR) due to chemotherapy, and to provide reference for rational use of antineoplastic drug and improve quality of life of patients. METHODS: 306 patients with malignant tumors were selected to investigate and analyze the effect of preventive medication, explore regularity of it and guide drug use in the clinic. RESULTS & CONCLUSION: Preventive medication could reduce ADR caused by chemotherapy, 5-HT amine played a significant role on reducing gastrointestinal side effects, and recombinant human granulocyte colony stimulating factor could prevent and treat myelosuppression induced by chemotherapy. Rational use of preventive medications can protect the smooth progress of chemotherapy, improve patient tolerance to chemotherapy, and enhance patient health.

  1. 慢性病病人药物治疗依从性调查及影响因素分析%Investigation of compliance with drugs in patients with chronic diseases and its influential factors

    Institute of Scientific and Technical Information of China (English)

    赵生俊; 范芳芳; 姚莉

    2011-01-01

    目的:调查新疆维吾尔自治区冠心病、高血压、糖尿病、类风湿性关节炎及哮喘这5种慢性病病人药物治疗依从性.方法:对600例慢性病病人进行问卷调查,并对用药依从性的影响因素进行分析,回收有效答卷452份,回收率75 3%.结果:哮喘病人依从性为32%,类风湿性关节炎病人依从性为67.2%,冠心病、高血压及糖尿病病人依从性在前两者之间.影响药物治疗依从性的因素包括老年病人、低文化层次、低收入、不同职业、哮喘病人、不规律复诊、药品种类、药品数量及其不良反应等.结论:多种因素可影响慢性病病人药物治疗依从性.%Objective: To investigate the compliance with drugs in patients with several chronic diseases, such as coronary heart disease, hypertension, diabetes, rheumatoid arthritis and asthma in Xinjiang Urgur autonomous region. Methods: The questionnaires were used in 600 patients. 452 questionnacres were returned(75. 3%). Results: The compliance of patients varied from 32.0% in asthma to 67. 2% in rheumatoid arthritis, and coronary heart disease, hypertension and diabetes came between asthma and rheumatoid arthritis. The influential factors of compliance included old age, low education, low paid occupation, asthma, irregularly consulting a doctor, categories of drugs or drug quantities, and adverse drug reactions. Conclusion: Various factors might influence compliance with drugs in patients with chronic diseases.

  2. To investigate the impact facots of dose of drug in intravenous infusion for decision-making%浅析静脉用药过程中影响药物剂量的护理因素及对策

    Institute of Scientific and Technical Information of China (English)

    卢桂华

    2012-01-01

    Objective To investigate the impact facots of dose of drug in intravenous infusion for decision-making. Methods 80 cases used of piperacillin tazobactam were randomly divided into control and experimental groups, using double-blind study, collection residual liquid of the original bottles and infusion tube, calculating drug dose, with daily infusion process in the control group, while strict intervention infusion process in experimental group. Average of drug residues between two groups with t-test. Results In control group, piperacillin tazobactam sodium content of the residual liquid average was(0. 9256 ± 0. 1189) g; experimental group ( 0. 2654 ± 0. 0398 ) g, P = 0. 000, the difference was statistically significant. Conclusion In intravenous drug preparation and the infusion process, strict rules of the nurses to reduce the residual liquid of drug.%目的 探讨静脉治疗过程中影响药物剂量的护理因素及对策.方法 80例输注哌拉西林钠他唑巴坦钠患者随机分为对照组和实验组,并采用双盲研究,收集原药瓶和输液器中的残留液计算残留药物剂量,对照组为护士日常输液流程,实验组为研究人员严格干预下输液流程.两组残留药物平均数进行t检验.结果 对照组残余药液平均含量为(0.9256±0.1189)g;实验组为(0.2654±0.0398)g(P=0.000),差异有统计学意义.结论 静脉药物配制及输液过程中,护理人员严格操作规程,可减少药液的残留.

  3. Investigation of infection satus of HIV, HCV and TP among 394 drug addicts in Cenxi City%岑溪市394例吸毒人员HIV、HCV、TP感染情况分析

    Institute of Scientific and Technical Information of China (English)

    陈洪森; 吕腾荣; 陈光英; 黄斌伟

    2012-01-01

    目的 了解掌握岑溪市吸毒人群的艾滋病病毒、丙型肝炎病毒、梅毒螺旋体感染情况,为该市艾滋病防治工作提供依据.方法 采用流行病学描述性研究方法对岑溪市394名吸毒人员人口、行为学资料分布情况分析;并开展艾滋病、丙肝、梅毒抗体检测,分析感染情况.结果 394例吸毒人员抗HIV、HCV、TP抗体阳性率分别为5.33%、80.96%、3.55%.30~岁组的HCV感染率高于≥40岁组.TP感染率女性高于男性.共针静脉注射吸毒者HCV感染率明显高于非共针静脉注射吸毒者.结论 岑溪市吸毒人群HIV、HCV、TP感染率较高,是重要的传染源之一,应加强对吸毒人群的监测、高危行为干预和健康教育.%Objective To investigate the infection status of HIV,HCV and TP among drug addicts in Cenxi city. Methods The demographic data and behavior of 394 drug addicts in Cenxi were analyzed with descriptive epidemiology. The antibody to HIV,HCV,TP were tested. Results The positive rate of anti-HIV, HCV, TP antibody of 394 drug addicts were 5.33%, 80.96%, and 3.55%, respectively. The HCV infection rate of 30-year-old age group was equal or higher than that of 40-year-old group. TP infection rate of the female was higher than male. Finally, the HCV infection rate of addicts sharing same needles was significantly higher than addicts who didn't. Conclusion The infection rate of HIV, HCV TP infection was relatively higher and drug user was one of the important sources of HIV, HCV and TP infection in Cenxi city. Thus monitoring drugs users, intervention of high—risk behavior and strengthening health education be earned out.

  4. Epigenetic Drugs for Multiple Sclerosis.

    Science.gov (United States)

    Peedicayil, Jacob

    2016-01-01

    There is increasing evidence that abnormalities in epigenetic mechanisms of gene expression contribute to the development of multiple sclerosis (MS). Advances in epigenetics have given rise to a new class of drugs, epigenetic drugs. Although many classes of epigenetic drugs are being investigated, at present most attention is being paid to two classes of epigenetic drugs: drugs that inhibit DNA methyltransferase (DNMTi) and drugs that inhibit histone deacetylase (HDACi). This paper discusses the potential use of epigenetic drugs in the treatment of MS, focusing on DNMTi and HDACi. Preclinical drug trials of DNMTi and HDACi for the treatment of MS are showing promising results. Epigenetic drugs could improve the clinical management of patients with MS.

  5. The spectroscopic properties of anticancer drug Apigenin investigated by using DFT calculations, FT-IR, FT-Raman and NMR analysis

    Science.gov (United States)

    Mariappan, G.; Sundaraganesan, N.; Manoharan, S.

    2012-09-01

    The FT-Raman and FT-Infrared spectra of solid Apigenin sample were measured in order to elucidate the spectroscopic properties of title molecule in the spectral range of 3500-50 cm-1 and 4000-400 cm-1, respectively. The recorded FT-IR and FT-Raman spectral measurements favor the calculated (by B3LYP/6-31G(d,p) method) structural parameters which are further supported by spectral simulation. Additional support is given by the collected 1H and 13C NMR spectra recorded with the sample dissolved in DMSO. The predicted chemical shifts at the B3LYP/6-31G(d) level obtained using the Gauge-Invariant Atomic Orbitals (GIAO) method with and without inclusion of solvent using the Polarizable Continuum Model (PCM). By using TD-DFT method, electronic absorption spectra of the title compound have been predicted and a good agreement with the TD-DFT method and the experimental one is determined. The UV-visible absorption spectra of the compound that dissolved in Ethanol, Methanol and DMSO were recorded in the range of 800-200 nm. The formation of hydrogen bond and the most possible interaction are explained using natural bond orbital (NBO) analysis. In addition, the molecular electrostatic potential (MEP), frontier molecular orbitals (FMO) analysis and atomic charges of the title compound were investigated using theoretical calculations. The results are discussed herein and compared with similar molecules whenever appropriate.

  6. 耐药菌感染调查与管理对策%Investigation and Management of Drug-resistant Bacteria Infection

    Institute of Scientific and Technical Information of China (English)

    胡泰欢

    2009-01-01

    OBJECTIVE To investigate antibiotic-resistant bacteria infection status of hospital patients and to propose management strategies to prevent the spread of antibiotic-resistant bacteria. METHODS Antibiotic-resistant bacteria infection status of hospital patients was investigated during Dec 2006 to June 2009. RESULTS 31 cases of infections occurred in 26 patients. Infection rate in hospital was 61.54%. and the death rate was 34.62%. In all parts of infection, lower respiratory tract infection reached 54.84%. Causes of infection includeed:severe diseases, long time of hospital stay, application of broad-spectrum antibiotics, invasive opera-tions and so on. Positive rate of antibiotic-resistant bacteria in wards was 9.91%, Contamination rate of medical supplies was 32.14%. The aggregation of multiple resistance bacteria was related to the contamination of medical supplies. CONCLUSIONS Supervision focus on hospital infection should be that strengthening the management of antibiotics, developing supervision of antibiotics-resistance of pathogens, ensuring disinfection and isolation methodstaking effects, standardizing operations of diagnostics and treatment and preventing spread of antibiotics-resistant bacteria in hospitals.%目的 对住院患者耐药菌感染情况进行调查,提出管理对策,防止耐药菌在医院内传播.方法 对医院2006年11月--2009年6月住院患者耐药菌感染情况进行现况调查.结果 同期住院患者耐药菌感染26例31例次,医院感染比例高达61.54%,死亡率占34.62%;感染部位下呼吸道感染发生率最高,占54.84%;感染危险因素包括:严重基础疾病、住院时间长、广谱抗菌药物使用、采用侵入性操作等;病区环境耐药菌的检出率为9.91%,诊疗用品的污染率为32.14%;多药耐药菌感染的聚集性发生,与诊疗器械污染密切相关.结论 加强对抗菌药物使用的管理,合理使用抗菌药物,防止细菌产生耐药性;积极开展感染病原菌及其

  7. Investigation and Analysis of Drug Labeling on Special Populations in 132 Package Inserts of TCM%132种中成药说明书中特殊人群用药标注情况的调查分析

    Institute of Scientific and Technical Information of China (English)

    赵丹

    2015-01-01

    目的 调查分析中成药说明书中特殊人群用药标注. 方法 对本院门诊中药房在用的132 份中成药说明书中特殊人群用药信息进行统计、分析. 结果 在用的132份中成药说明书中对妊娠期及哺乳期妇女用药、儿童用药、其他特殊人群用药进行了说明的分别为53.03%,5.30%和40.15%,完全没有特殊人群用药标注为23.48%. 结论 目前中成药说明书对特殊人群用药信息的标注存在信息量不足或过于简单,应进一步完善其说明书管理.%Objective To investigate and annlyze the drug labeling on special populations.Method To analyze each items of information on special populations in 132 package inserts of TCM.Results Drug use information for pregnant and lactating women,children,and other special populations respectively for 53.03%,5.30%and 40.15%,no drug use information for these three types of special populations for 23.48%.Conclusion There are some problems about package inserts of TCM,such as inadequate information and simple.To ensure safe use,the package inserts of TCM should be further improved.

  8. A New Approach for Investigating the Molecular Recognition of Protein: Toward Structure-Based Drug Design Based on the 3D-RISM Theory.

    Science.gov (United States)

    Kiyota, Yasuomi; Yoshida, Norio; Hirata, Fumio

    2011-11-08

    A new approach to investigate a molecular recognition process of protein is presented based on the three-dimensional reference interaction site model (3D-RISM) theory, a statistical mechanics theory of molecular liquids. Numerical procedure for solving the conventional 3D-RISM equation consists of two steps. In step 1, we solve ordinary RISM (or 1D-RISM) equations for a solvent mixture including target ligands in order to obtain the density pair correlation functions (PCF) among molecules in the solution. Then, we solve the 3D-RISM equation for a solute-solvent system to find three-dimensional density distribution functions (3D-DDF) of solvent species around a protein, using PCF obtained in the first step. A key to the success of the method was to regard a target ligand as one of "solvent" species. However, the success is limited due to a difficulty of solving the 1D-RISM equation for a solvent mixture, including large ligand molecules. In the present paper, we propose a method which eases the limitation concerning solute size in the conventional method. In this approach, we solve a solute-solute 3D-RISM equations for a protein-ligand system in which both proteins and ligands are regarded as "solutes" at infinite dilution. The 3D- and 1D-RISM equations are solved for protein-solvent and ligand-solvent systems, respectively, in order to obtain the 3D- and 1D-DDF of solvent around the solutes, which are required for solving the solute-solute 3D-RISM equation. The method is applied to two practical and noteworthy examples concerning pharmaceutical design. One is an odorant binding protein in the Drosophila melanogaster , which binds an ethanol molecule. The other is phospholipase A2, which is known as a receptor of acetylsalicylic acid or aspirin. The result indicates that the method successfully reproduces the binding mode of the ligand molecules in the binding sites measured by the experiments.

  9. IDENTIFICATION OF DRUG ADDICTION AND RESEARCH ON DRUG CONTROL SOCIAL WORK-FURTHER INVESTIGATION ON DRUG REHABILITATION RATE AND RELAPSE RATE%认定戒断毒瘾工作与禁毒社会工作研究一戒断率与复吸率探讨

    Institute of Scientific and Technical Information of China (English)

    杨增余; 沙祖龙

    2011-01-01

    This paper summarized the experiences of drug control social work in Yangpu District Shanghai. It showed that with the cooperation of anti - drug agency and police department, how the drug control social workers in the district applied their social work principles, theoretical mode and professional treatment in helping targets to get rid of drug addiction and increase their social function through incorporating social resources. It also pointed out that professional treatment such as case management, group work and domestic societal work should be used to increase drug rehabilitation rate and decrease relapse rate. Therefore, suggestions and strategies are proposed for the establishment and improvement of integration of employment and heath care systems.%本文通过上海市杨浦区开展禁毒社会工作后,禁毒社会工作者配合禁毒办、公安局开展认定工作,在认定中运用社会工作的价值观、理论模式、专业方法,整合社会资源,使服务对象摆脱对毒品的依赖,提高戒断率,提升服务对象的社会功能.指出:要提高戒断率、降低复吸率,应运用个案、小组、家庭等专业方法;从建立和完善就业、就医机制等进行系统性整合,提出相关对策和建议.

  10. Orphan drugs

    Directory of Open Access Journals (Sweden)

    Goločorbin-Kon Svetlana

    2013-01-01

    Full Text Available 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 drugs meant to treat diseases whose pathogenesis has not yet been clarified in majority of cases. The aim of this paper is to present previous and present status of orphan drugs in Serbia and other countries. The beginning of orphan drugs development. This problem was first recognized by Congress of the United States of America in January 1983, and when the ”Orphan Drug Act” was passed, it was a turning point in the development of orphan drugs. This law provides pharmaceutical companies with a series of reliefs, both financial ones that allow them to regain funds invested into the research and development and regulatory ones. Seven years of marketing exclusivity, as a type of patent monopoly, is the most important relief that enables companies to make large profits. Conclusion. There are no sufficient funds and institutions to give financial support to the patients. It is therefore necessary to make health professionals much more aware of rare diseases in order to avoid time loss in making the right diagnosis and thus to gain more time to treat rare diseases. The importance of discovery, development and production of orphan drugs lies in the number of patients whose life quality can be improved significantly by administration of these drugs as well as in the number of potential survivals resulting from the treatment with these drugs. [Projekat Ministarstva nauke Republike Srbije, br. III 41012

  11. Club Drugs

    Science.gov (United States)

    ... Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/Nicotine Other Drugs Related Topics Addiction Science Adolescent Brain Comorbidity College-Age & Young Adults ...

  12. 女性吸毒者艾滋病相关知识及高危性行为调查%Investigation on AIDS related knowledge and high risk sex behaviors among female drug abusers

    Institute of Scientific and Technical Information of China (English)

    王玮; 任桂秋; 肇恒伟; 赵子阳

    2012-01-01

    Objective; To understand the awareness situation of AIDS related knowledge and high risk sex behaviors among female drug abusers. Methods: Stratified random cluster sampling method and questionnaire survey were used to investigate 236 female drug abusers in Liaoning province, 1: 1 matched case - control study was carried out, female prison inmates during the same period were selected as control group, then they were surveyed by a questionnaire, Logistic regression analysis was used to analyze the influencing factors of high risk sex behaviors among female drug abusers. Results: The mean correct awareness rate of AIDS related knowledge among female drug abusers was 57. 6% , 69. 9% of the respondents had multiple sexual partners, and 69. 1% of the respondents never used condom; the results of mult-ivariate Logistic regression analysis showed that the scores of intravenous drug abuse and basic knowledge of AIDS were low, the respondents with low positive attitude to condom were easily to have high risk sex behaviors. Conclusion: The female drug abusers had misunderstanding toward AIDS related knowledge and attitudes, it is necessary to carry out interventional strategies targeting to their high risk sex behaviors.%目的:了解女性吸毒者艾滋病相关知识的知晓情况和高危性行为情况.方法:采用分层、随机、整群抽样相结合的方法对辽宁省236例女性吸毒者进行问卷调查,同时采用1:1病例对照研究方法,选择同期调查中女性监所服刑人员作为对照进行问卷调查,应用Logistic回归分析对女性吸毒者高危性行为的影响因素进行分析.结果:女性吸毒者艾滋病相关知识平均答对率为57.6%,69.9%的调查者与多个性伙伴发生性行为,69.1%的调查者从未使用安全套;多因素Logistic回归结果显示,静脉注射吸毒、艾滋病基本知识得分低,以及对安全套正性态度较低者更容易发生高危性行为.结论:女性吸毒者对艾滋病相关

  13. Herbal drugs and drug interactions

    OpenAIRE

    Gül Dülger

    2014-01-01

    Herbal drugs are defined as any form of a plant or plant product that contains a single herb or combinations of herbs that are believed to have complementary effects. Although they are considered to be safe, because they are natural, they may have various adverse effects, and may interact with other herbal products or conventional drugs. These interactions are especially important for drugs with narrow therapeutic indices.In the present study, pharmacokinetic and pharmacodynamic interactions ...

  14. Drugged Driving

    Science.gov (United States)

    ... Age Adults in 2015 Teens and E-cigarettes Abuse of Prescription (Rx) Drugs Affects Young Adults Most Substance Use in Women and Men View All NIDA's Publication Series Brain Power DrugFacts Mind Over Matter Research Reports NIDA Home ...

  15. Drug treatment

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    2010263 Drug resistance mechanism of non-small cell lung cancer PC9/AB2 cell line with acquired drug resistance to gefitinib.JU Lixia(鞠立霞),et al. Dept Oncol,Shanghai Pulm Hosp,Tongji Univ,Shanghai 200433. Chin J Tuberc Respir Dis 2010;33(5):354-358. Objective To

  16. Drug Education.

    Science.gov (United States)

    Sardana, Raj K.

    This autoinstructional lesson deals with the study of such drugs as marijuana and LSD, with emphasis on drug abuse. It is suggested that it can be used in science classes at the middle level of school. No prerequisites are suggested. The teacher's guide lists the behavioral objectives, the equipment needed to complete the experience and suggests…

  17. Preformulation and Formulation Investigational New Drugs

    Science.gov (United States)

    1990-07-01

    pyridostigmine. Formulation Strate~y Since hydroxypropylmethylcellulose (HPMC) and hydrogenated castor oil (Castorwax@)/polyvinylpyrolidone (PVP) had been used... hydroxypropylmethylcellulose (MethocelO K4M CR) for 10 minutes in a V-blender. Povidone was added to this mixture and blended for a further 10 minutes. The

  18. ICU深静脉导管感染的病原菌分布和耐药性分析%Investigation of distribution and drug resistance of pathogenic bacteria causing deep venous catheter related infection in ICU

    Institute of Scientific and Technical Information of China (English)

    李静; 周利霞; 范秋生

    2012-01-01

    Objective To investigate the characteristics of distribution and drug resistance of pathogenic bacteria causing deep venous catheter related infection in ICU.Methods From January 2006 to August 2010,the culture and drug sensitivity test results of 342 deep venous catheter tip from ICU were analyzed retrospectively. Results Among the results of 342 catheter tip cultures,101 strains( 29. 5% )of pathogenic bacteria were detected. The proportion of G+ bacteria,enterobacteria ceae,non-fermentation G- bacteria and fungi was 29 strains( 28.7% ),25 strains( 24. 8% ),33 strains( 32. 6% )and 14 strains ( 13.9% )respectively. The six most common pathogenic bacteria were pseudomonas aeruginosa 20 strains( 19.8% ), Klebsiella pneumonia 12 strains( 11.9% ),Staphylococcus aureus 10 strains( 9. 9% ), Staphylococcus epidermis 8 strains( 7. 9% ),En-terococcus faecium 7 strains( 6. 9% ) and Saccharomyces albicans 7 strains( 6. 9% ). 8 strains( 80. 0% )of Staphylococcus aureus were MRSA,7 strains( 63. 6% )of coagulase negative Staphylococci were MRCNS and 14 strains( 56. 0% )of Enterobacte-riaceae were ESBLs. Most isolated strains were multiple drug resistant. Conclusion The most common pathogens cultured from the deep venous catheter tip in ICU were highly resistant to antibiotics. The clinical micro-organisms laboratory should report the results of bacterial culture and drug susceptibility quickly and accurately for reasonable use of antibiotic drugs in clinical treatment.%目的 探讨ICU深静脉导管感染的病原菌分布和细菌耐药性特征.方法 对2006年1月-2010年8月ICU送检的342例次深静脉导管标本的细菌培养和药敏试验结果进行分析.结果 342份标本中共检出病原菌101株(29.5%):革兰阳性球菌、肠杆菌科、非发酵革兰阴性杆菌和真菌分别为29株(28.7%)、25株(24.8%)、33株(32.6%)和14株(13.9%).病原菌分离率前6位依次为铜绿假单胞菌20株(19.8%)、肺炎克雷伯菌12株(11.9%)

  19. 21 CFR 312.21 - Phases of an investigation.

    Science.gov (United States)

    2010-04-01

    ... of drug metabolism, structure-activity relationships, and mechanism of action in humans, as well as... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE INVESTIGATIONAL NEW DRUG APPLICATION Investigational New Drug Application (IND) §...

  20. Intracerebroventricular administration of drugs.

    Science.gov (United States)

    Cook, Aaron M; Mieure, Katherine D; Owen, Robert D; Pesaturo, Adam B; Hatton, Jimmi

    2009-07-01

    Intracerebroventricular drug administration is a method that bypasses the blood-brain barrier and other mechanisms that limit drug distribution into the brain, allowing high drug concentrations to enter the central compartment. Instillation of drugs directly into the ventricles of the brain must be done carefully and with full consideration of factors affecting the efficacy and safety of this route of administration. These factors include the osmolarity, pH, volume, and presence of preservatives and diluents of the drug solution being administered. Very few studies have formally investigated intraventricular therapies, and dosing recommendations may vary widely depending on the agent and the patient. Many antimicrobials have been given intraventricularly, although very few prospective studies have evaluated this strategy. There are wide variations among the reports regarding dosage regimens and the pharmacokinetics of the antimicrobials used. Guidance on appropriate formulations and their use is lacking. Clinicians should be aware of their patients' ongoing disease processes and neurologic status, as well as pertinent physiochemical properties of drugs when formulating them for intracerebroventricular administration; a high index of suspicion should be maintained when monitoring patients for adverse drug events after instillation.

  1. Discussion on Investigation on Illegal Cases of Fake and InferiorVeterinary Drugs Transportation in Logistics and Express Industry%查处物流快递涉假劣兽药违法案件的讨论

    Institute of Scientific and Technical Information of China (English)

    刘雪萍; 李昌主

    2015-01-01

    In recent years,with strong convert,low cost,high efficiency of logistics and express industry,the illegal cases of transport fake and inferior veterinary drugs with logistics and express,which are hard to investigate and penalize,have been increasing year by year. This paper analyzed the problems in such illegal cases and made suggestions of routine law enforcement,investigation and inspection,case clue collection,collaboration of various department,participation of public,etc.,as to strengthen supervision,and make good orders of the regional veterinary medicine market.%不法分子利用物流快递隐蔽性强、成本低、效率高等特点,进行非法托运、贩运假劣兽药的案件数量逐年上升。该类案件的查处和定罪难度较大。本文分析了假劣兽药监管在物流快递业中存在的问题,提出在日常执法、调查取证、线索收集、部门联合、公众参与等方面加强监管,净化区域兽药经营的市场秩序的建议。

  2. 大输液包装材质与注射用药物相容性研究进展与思考%Research Advance and Investigation on Compatibility of Large Volume Parenteral Solution Package Material with Injectable Drugs

    Institute of Scientific and Technical Information of China (English)

    徐帆; 杨伶俐; 毛盼盼; 喻琼丽

    2014-01-01

    目的:促进临床合理用药。方法调研相关文献,分析不同包装材质大输液的性质、特点及其对注射用药物的吸附性作用。结果与结论大输液作为临床治疗和静脉药物治疗不可缺少的载体或溶剂,在现代临床治疗中具有极其重要的地位,临床医务人员已逐渐开始关注药物与大输液包装材质的相容性与安全性。目前,我国医疗市场多种材质包装的大输液并存。临床医务人员应更加准确地把握不同包装材质大输液的特性,静脉用药物治疗时选择适当包装材质的大输液,以确保患者输液安全。%Objective To promote the rational drug use. Methods By investigating and consulting the related literature,the properties, characteristics and adsorptive effect on injectable drugs of the large volume parenteral solution package materials were analyzed. Results and Conclusion The large volume parenteral solution as the indispensable carrier or solvent possesses the extreme important status in the modern clinical treatment. The clinical medical staffs have gradually begin to pay close attention to the compatibility and safety of drugs and the large volume parenteral solution package materials. At present,the large volume parenteral solutions packaged by various materials coexist in the medical market of our country. The clinical medical staffs should more accurately grasp the characteristics of the large volume parenteral solutions with different package materials. Intravenous medication should select the large volume parenteral solu-tions with the proper package materials for ensuring the intravenous infusion safety of patients.

  3. 2009-2012年广西 HIV-1耐药状况调查%Investigation of the HIV-1 drug resistance in Guangxi during 2009 to 2012

    Institute of Scientific and Technical Information of China (English)

    刘洁; 黄颉刚; 梁浩; 叶力; 梁冰玉; 周波; 王敏连; 赵芳凝; 陈荣凤; 王洪; 潘沛江; 蒋俊俊

    2015-01-01

    目的:调查2009—2012年广西HIV-1感染者的耐药状况,同时探讨耐药与亚型的关系。方法在广西各地随机募集HIV/AIDS患者,提取患者血液样本的HIV RNA,逆转录后扩增pol基因并测序,使用在线分析工具Genotyping结合MEGA 5.03软件进行亚型分型,使用斯坦福大学的HIV耐药数据库确定耐药突变位点及药物耐受情况。结果获得196份pol区序列,其中接受抗病毒治疗样本103例(52.55%),未经治疗样本93例(47.45%);亚型分布为95例CRF01_AE(48.47%)、88例CRF08_BC(44.90%)、12例CRF07_BC(6.12%)以及1例B亚型(0.51%);接受抗病毒治疗患者耐药率为10.68%,未经治疗患者耐药率为7.53%;在196例研究对象中发现低度耐药14例,中度耐药3例,高度耐药4例;1例针对核苷类逆转录酶抑制剂( NRTIs )和非核苷类逆转录酶抑制剂(NNRTIs)发生二重耐药;不同类型药物耐药结果:蛋白酶抑制剂(PIs)、NRTIs、NNRTIs及整合酶抑制剂(INs)相关耐药率分别为6.63%、3.06%、11.22%、8.67%;CRF01_AE、CRF07_BC和CRF08_BC亚型发生PIs相关突变的频率分别为6.32%、41.67%和2.27%;A71V/T在CRF07_BC毒株中出现最多(75%),E138A仅出现在CRF08_BC毒株中(100%)。结论广西HIV-1患者耐药发生率高于全国水平,不同亚型HIV-1流行株的耐药发生率不同。%Objective To investigate the HIV-1 drug resistance in Guangxi during 2009 to 2012 and to analyze the correlations between drug resistance and HIV-1 subtypes.Methods Patients with human immunodeficiency virus infection or acquired immune deficiency syndrome ( HIV/AIDS) were randomly re-cruited from different areas in Guangxi.HIV-1 RNA was extracted from blood samples of the subjects and converted into complementary DNA ( cDNA) by using reverse transcription.The pol gene was amplified and

  4. Incidence of potential drug-drug interactions with antidiabetic drugs.

    Science.gov (United States)

    Samardzic, I; Bacic-Vrca, V

    2015-06-01

    In an effort to achieve normoglycemia more than one antidiabetic agent is usually needed. Diabetes is associated with several comorbidities and patients with diabetes are often treated with multiple medications. Therefore, patients with diabetes are especially exposed to drug-drug interactions (DDIs). The aim of this study was to analyse the incidence and type of potential DDIs of antidiabetic drugs in patients with diabetes. This retrospective study analyzed pharmacy record data of 225 patients with diabetes mellitus. Both type 1 and type 2 diabetic patients who were taking at least one antidiabetic agent during the period of six months were included. We investigated associated therapy in that period in order to identify potential DDIs with antidiabetic therapy. Potential interactions were identified by Lexicomp Lexi-Interat Online (Lexi-Comp, Inc., Hudson, USA) software which categorizes potential DDIs according to clinical significance in five types (A, B, C, D and X). Categories C, D and X are of clinical concern and always require medical attention (therapy monitoring, therapy modification or avoiding combination). We found that 80.9% of patients had at least one potential category C interaction while there were no D and X interactions. Most frequently encountered potential DDI (n = 176) included antidiabetic drugs and thiazide or thiazide like diuretics. Patients with diabetes are exposed to a large number of potential clinically significant DDIs that may require appropriate monitoring. Using databases of DDIs could be helpful in reducing the risk of potential clinically significant DDIs.

  5. Drug Facts

    Medline Plus

    Full Text Available ... Cocaine (Coke, Crack) Facts Heroin (Smack, Junk) Facts Marijuana (Weed, Pot) Facts MDMA (Ecstasy, Molly) Facts Meth (Crank, ... Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine ...

  6. Drug Facts

    Medline Plus

    Full Text Available ... Link Between Drug Use and HIV/AIDS Treatment & Recovery What is Treatment? Why Does a Person Need ... Work? What Are the Treatment Options? What Is Recovery? What Is a Relapse? How Can Friends and ...

  7. Drug Facts

    Medline Plus

    Full Text Available ... That People Abuse Alcohol Facts Bath Salts Facts Cocaine (Coke, Crack) Facts Heroin (Smack, Junk) Facts Marijuana ( ... Watch Videos Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) ...

  8. Drug Facts

    Medline Plus

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

  9. Drug Facts

    Medline Plus

    Full Text Available ... Facts Bath Salts Facts Cocaine (Coke, Crack) Facts Heroin (Smack, Junk) Facts Marijuana (Weed, Pot) Facts MDMA ( ... Videos Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/ ...

  10. Drug Addiction

    Science.gov (United States)

    ... stimulants Stimulants include amphetamines, meth (methamphetamine), cocaine and methylphenidate (Ritalin). They are often used and abused in ... a medication, talk to your doctor. Preventing drug abuse in children and teenagers Take these steps to ...

  11. Antiretroviral drugs.

    Science.gov (United States)

    De Clercq, Erik

    2010-10-01

    In October 2010, it will be exactly 25 years ago that the first antiretroviral drug, AZT (zidovudine, 3'-azido-2',3'-dideoxythymidine), was described. It was the first of 25 antiretroviral drugs that in the past 25 years have been formally licensed for clinical use. These antiretroviral drugs fall into seven categories [nucleoside reverse transcriptase inhibitors (NRTIs), nucleotide reverse transcriptase inhibitors (NtRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), fusion inhibitors (FIs), co-receptor inhibitors (CRIs) and integrase inhibitors (INIs). The INIs (i.e. raltegravir) represent the most recent advance in the search for effective and selective anti-HIV agents. Combination of several anti-HIV drugs [often referred to as highly active antiretroviral therapy (HAART)] has drastically altered AIDS from an almost uniformly fatal disease to a chronic manageable one.

  12. Drug Facts

    Medline Plus

    Full Text Available ... That People Abuse Alcohol Facts Bath Salts Facts Cocaine (Coke, Crack) Facts Heroin (Smack, Junk) Facts Marijuana ( ... Watch Videos Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) ...

  13. Drug Facts

    Medline Plus

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

  14. Prescription Drugs

    Science.gov (United States)

    ... Jackets, Yellows, and Zombie Pills Stimulants: Bennies, Black Beauties, Hearts, Roses, Skippy, The Smart Drug, Speed, and ... used to relieve anxiety or help a person sleep, such as Valium or Xanax Stimulants — used for ...

  15. Drug Facts

    Medline Plus

    Full Text Available ... Cocaine (Coke, Crack) Facts Heroin (Smack, Junk) Facts Marijuana (Weed, Pot) Facts MDMA (Ecstasy, Molly) Facts Meth ( ... Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine ...

  16. ENHANCED BIOAVAILABILITY OF DRUGS VIA INTRANASAL DRUG DELIVEY SYSTEM

    Directory of Open Access Journals (Sweden)

    kumar Brajesh

    2012-07-01

    Full Text Available The aim of present investigation is to explain the enhancement of bioavailability of drug through intranasal drug delivery system. Intranasal Therapy has been an accepted form of treatment in the Ayurvedic system of Indian Medicine. Recently, it has been shown that many drugs have better bioavailability by nasal route than the oral route. This has been attributed to rich vasculature and a highly permeable structure of the nasal mucosa coupled with avoidance of hepatic first-pass elimination, gut wall metabolism and/or destruction in the gastrointestinal tract. Intranasal microemulsion, gels, nanoparticles, liposome and microspheres have gained increased interest in recent years as a delivery system for protein and peptides through the nasal route. Thus this review focuses on nasal drug delivery, nasal drug absorption mechanisms, various mechanisms for increasing the bioavailability of drug, and their applications in drug delivery.

  17. Drug-drug interactions: antiretroviral drugs and recreational drugs.

    Science.gov (United States)

    Staltari, Orietta; Leporini, Christian; Caroleo, Benedetto; Russo, Emilio; Siniscalchi, Antonio; De Sarro, Giovambattista; Gallelli, Luca

    2014-01-01

    With the advances in antiretroviral (ARV) therapy, patients with Human Immunodeficiency Virus (HIV) infection are living longer, however, some patients encounter co- morbidities which sometimes require treatment. Therefore, during the treatment with ARV drugs these patients could take several recreational drugs (e.g. amphetamines, hallucinogenes, opiates, or alcohol) with a possible development of drug-drug interactions (DDIs). In particular, Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs/NtRTIs) are mainly excreted through the kidney and are not substrates of the cytochrome P450 or P-glycoprotein, therefore the DDIs during this treatment are minimal. In contrast, the other ARV drugs (i.e. non-nucleoside reversetranscriptase inhibitors, Protease inhibitors, Integrase inhibitors, chemokine receptor 5 antagonists and HIV-fusion inhibitors) are an important class of antiretroviral medications that are frequent components of HAART regimens but show several DDIs related to interaction with the cytochrome P450 or P-glycoprotein. In this paper we will review data concerning the possibility of DDI in HIV patients treated with ARV and taking recreational drugs.

  18. One-day Investigation of Psychotropic Drugs Use for 149 Inpatients in the Psychosomatic Disorder Department%149例心身障碍科住院患者1日精神药物使用调查

    Institute of Scientific and Technical Information of China (English)

    章凤君; 陈晓燕; 孙皎

    2013-01-01

    Objective: To investigate the one-day use of psychotropic drugs for the patients in the psychosomatic disorder department, and provide guidance for clinical rational medication. Methods: Prescriptions of 149 inpatients were investigated in the psychosomatic disorder department on May 8, 2012 through Hospital Information System (HIS). Results: Top five prescriptions of antidepressants were respectively paroxetine 35(23.49% ) , sertraline 21 ( 14.09% ) , escita-lopram 19(12. 75%) , mirtazapine 17(11.41%) and venlafaxine 15(10. 07%), while the top five anxiolytics were clon-azepam 130(87.25% ) , buspirone hydrochloride 16( 10.74% ), lorazepam 14(9.40% ) , alprazolam 10(6.71% ) and ox-azepam 6(4. 03% ) in order. The antipsychotics that were used most frequently were Sulpiride 68(45. 64% ) , followed by quetiapine 33(22. 15% ), olanzapine 16( 10. 74% ) , risperidone 7(4.70% ) and aripiprazole 3(2.01% ). Simultaneously , inpatients often received a combination of two or three different drugs above in the psychosomatic disorder department. Conclusion: The new generation of antidepressants and anxiolytics which were safe and had fewer side effects were mainly utilized in the psychosomatic disorder department. Most prescriptions in the one - day investigation were rational. However, some problems should be seriously considered, such as high prevalence of Benzodiazepines use, excessive drug combination and lack of the non-medical therapy.%目的:调查某院心身障碍科1日用药情况,为临床合理用药提供客观数据.方法:统计该院心身障碍科2012年5月8日149例住院患者用药信息.结果:抗抑郁药使用频次依次为帕罗西汀35例(23.49%)、舍曲林21例(14.09%)、艾司西酞普兰19例(12.75%)、米氮平17例(11.41%)、文拉法辛15例(10.07%);镇静催眠抗焦虑药前5位的是氯硝西泮130例(87.25%)、丁螺环酮16例(10.74%)、劳拉西泮14例(9.40%)、阿普唑仑10例(6.71%)、奥沙西泮6例(4.03

  19. Image Guided Biodistribution of Drugs and Drug Delivery

    OpenAIRE

    Ding, Hong; Wu, Fang

    2012-01-01

    Image guided technique is playing an increasingly important role in the investigation of the biodistribution and pharmacokinetics of drugs or drug delivery systems. The application of these new materials and techniques with combined properties of diagnosis and therapy can benefit the development of targeted drug delivery system and modern personalized medicine This special issue provides an up-to-date collection of original research articles and review on the development of novel targeted dru...

  20. COPD - control drugs

    Science.gov (United States)

    Chronic obstructive pulmonary disease - control drugs; Bronchodilators - COPD - control drugs; Beta agonist inhaler - COPD - control drugs; Anticholinergic inhaler - COPD - control drugs; Long-acting inhaler - COPD - ...

  1. Herbal drugs and drug interactions

    Directory of Open Access Journals (Sweden)

    Gül Dülger

    2012-01-01

    Full Text Available Herbal drugs are defined as any form of a plant or plant product that contains a single herb or combinations of herbs that are believed to have complementary effects. Although they are considered to be safe, because they are natural, they may have various adverse effects, and may interact with other herbal products or conventional drugs. These interactions are especially important for drugs with narrow therapeutic indices.In the present study, pharmacokinetic and pharmacodynamic interactions of some most commanly used herbals (St John's wort, ginkgo biloba, ginseng, ginger, garlic, echinacea, ephedra and valerian with the conventional drugs were reviewed. Pharmacokinetic interactions involve mainly induction or inhibition of the cytochrome P450 isozymes and p-glycoproteins by the herbal medicine, thus changing the absorption and/or elimination rate and consequently the efficacy of the concommitantly used drugs. St John's wort, a well known enzyme inducer, decreases the efficacy of most of the other drugs that are known to be the substrates of these enzymes.Pharmacodynamic interactions may be due to additive or synergistic effects which results in enhanced effect or toxicity, or herbal medicines with antagonistic properties reduce drug efficacy and result in therapeutic failure. For exampla, St John's wort may have synergistic effects with other antidepressant drugs used by the patient, resulting in increased CNS effects.Herbals like ginseng, ginkgo, garlic, ginger were reported to increase bleeding time, thus potentiating the effect of anticoagulant and antithrombotic agents. In conclusion, patients should be warned against the interaction between the herbal products and conventional medicines.

  2. Investigation of the Public Recognition and Demand for Propaganda of Rational Drug Use%社会公众对合理用药宣传的认知和需求调查

    Institute of Scientific and Technical Information of China (English)

    洪兰; 叶佩芸; 王莉; 叶桦

    2016-01-01

    OBJECTIVE:To provide reference for improving propaganda level and effect of rational drug use. METHODS:Questionnaire survey was designed to investigate the recognition,attitude and demand of consumers in retail pharmacies,students in parts of pharmaceutical universities and their parents and patients in parts of hospitals in more than 10 provinces(autonomous re-gions and municipalities)for propaganda of rational drug use,and the results were statistically significant. RESULTS:The question-naires ranged from 100 to 2 000 in each province (autonomous region and municipality),and totally 11 700 questionnaires were sent out,11 490 were received with recovery of 98.2%;10 980 were effectively received with effective recovery of 95.6%. 78.4%respondents heard of the concept of rational drug use,proportion of young and middle-aged people in 18-44 years old was signifi-cantly higher than other age group,the proportion was significantly increased by the improvement of education,and the proportion of people closer to the city was higher(P<0.001);the respondents who can fully understand the content of the propaganda account-ed for 22.7%,while higher education held higher proportion on“fully understand”,and people closer to the city held higher pro-portion on“fully understand”and“partially understand”(P<0.001);only 9.5% respondents could fully trust propaganda activity, proportion of choosing“partially trust”was generally increased by the improvement of education(P<0.001);and 69.1% respon-dents hoped to obtain relevant knowledge,people who had more purchase frequencies showed stronger willing(P<0.001);the top 3 preferences of respondents for propaganda forms were“face to face guidance from physicians and pharmacists”,“reading drug in-structions”and“reading professional books”. CONCLUSIONS:With insufficient recognition on rational use of drugs,coverage of propaganda about rational drug use needs further expand,public understanding of propaganda

  3. Investigation on AIDS-related KAP in female sex workers and clients (drug users)%吸毒者中暗娼与嫖客艾滋病相关KAP调查分析

    Institute of Scientific and Technical Information of China (English)

    周翔; 郑武; 刘旺民

    2011-01-01

    Objective To investigate the AIDS related KAP in female sex workers and clients, in particular, drug users, so as to provide basis for health education and behavioral intervention. Methods Basic information and KAP of sex workers and clients from drug rehabilitation centers were investigated, self-designed questionnaire was performed and cluster sampling method was applied. Results In terms of relevant knowledge of AIDS ,80.49% female sex workers thought that the use of condom could prevent AIDS;31.71% of female sex workers thought that the danger of AIDS was far away from them, and 28. 57% of clients had the similar idea( P < 0.05 ). The understanding rate of the AIDS transmission path in the female sex workers and clients was rather low,except that mother-infant breast-feeding path of HIV transmission,the difference was of statistical significance. The ratio of female sex workers resisting sexual freedom was significantly higher than that of the clients ( P < 0.05 ) ; The ratio of sex workers using condom was significantly higher than that of the clients ( P < 0.05). Conclusions Priority should be put on male high-risk group while carrying out the condom-use education and intervention for HIV prevention. Psychological, sexual moral publicity and AIDS-related knowledge education should be reinforced and the intervention of high-risk sexual behavior should be emphasized, in particular, among the drug-using group, including female sex workers and clients.%目的 了解吸毒者中暗娼与嫖客KAP现状,为该类人群的健康教育、行为干预提供依据.方法 应用自行设计的调查问卷,采取整群抽样的方法,对某戒毒所吸毒人员中暗娼与嫖客基本情况、KAP等进行调查分析.结果 艾滋病相关知识的掌握,80.49%的暗娼认为使用安全套可以预防艾滋病;31.71%的暗娼和28.57%的嫖客认为艾滋病离我们很远;暗娼和嫖客对传播途径的知晓率比较,除HIV阳性

  4. Why Are Drugs So Hard to Quit?

    Medline Plus

    Full Text Available ... in the Brain, Animation. - Duration: 4:16. Alila Medical Media 306,274 views 4:16 Top 10 Most ... Investigating Drug Abuse: Brain Imaging - Duration: 1:51. National Institute on Drug Abuse ( ...

  5. Prospective Preliminary In Vitro Investigation of a Magnetic Iron Oxide Nanoparticle Conjugated with Ligand CD80 and VEGF Antibody As a Targeted Drug Delivery System for the Induction of Cell Death in Rodent Osteosarcoma Cells.

    Science.gov (United States)

    Kovach, AnneMarie Kay; Gambino, Jen M; Nguyen, Vina; Nelson, Zach; Szasz, Taylor; Liao, Jun; Williams, Lakiesha; Bulla, Sandra; Prabhu, Raj

    2016-01-01

    Target drug deliveries using nanotechnology are a novel consideration in the treatment of cancer. We present herein an in vitro mouse model for the preliminary investigation of the efficacy of an iron oxide nanoparticle complex conjugated to vascular endothelial growth factor (VEGF) antibody and ligand cluster of differentiation 80 (CD80) for the purpose of eventual translational applications in the treatment of human osteosarcoma (OSA). The 35 nm diameter iron oxide magnetic nanoparticles are functionalized with an n-hydroxysuccinimide biocompatible coating and are conjugated on the surface to proteins VEGF antibody and ligand CD80. Combined, these proteins have the ability to target OSA cells and induce apoptosis. The proposed system was tested on a cancerous rodent osteoblast cell line (ATCCTM(NPO) CRL-2836) at four different concentrations (0.1, 1.0, 10.0, and 100.0 μg/mL) of ligand CD80 alone, VEGF antibody alone, and a combination thereof (CD80+VEGF). Systems were implemented every 24 h over different sequential treatment timelines: 24, 48, and 72 h, to find the optimal protein concentration required for a reduction in cell proliferation. Results demonstrated that a combination of ligand CD80 and VEGF antibody was consistently most effective at reducing aberrant osteoblastic proliferation for both the 24- and 72-h timelines. At 48 h, however, an increase in cell proliferation was documented for the 0.1 and 1 μg/mL groups. For the 24- and 72-h tests, concentrations of 1.0 μg/mL of CD80+VEGF and 0.1 μg/mL of VEGF antibody were most effective. Concentrations of 10.0 and 100.0 μg/mL of CD80+VEGF reduced cell proliferation, but not as remarkably as the 1.0 μg/mL concentration. In addition, cell proliferation data showed that multiple treatments (72-h test) induced cell death in the osteoblasts better than a single treatment. Future targeted drug delivery system research includes trials in OSA cell lines from greater phylum species having

  6. Prospective Preliminary In Vitro Investigation of a Magnetic Iron Oxide Nanoparticle Conjugated with Ligand CD80 and VEGF Antibody As a Targeted Drug Delivery System for the Induction of Cell Death in Rodent Osteosarcoma Cells

    Directory of Open Access Journals (Sweden)

    Anne Marie Kay Kovach

    2016-10-01

    Full Text Available Target drug deliveries using nanotechnology are a novel consideration in the treatment of cancer. We present herein an in vitro mouse model for the preliminary investigation of the efficacy of an iron oxide nanoparticle complex conjugated to vascular endothelial growth factor (VEGF antibody and ligand cluster of differentiation 80 (CD80 for the purpose of eventual translational applications in the treatment of human osteosarcoma (OSA. The 35 nm diameter iron oxide magnetic nanoparticles are functionalized with an n-hydroxysuccinimide biocompatible coating and are conjugated on the surface to proteins VEGF antibody and ligand CD80. Combined, these proteins have the ability to target OSA cells and induce apoptosis. The proposed system was tested on a cancerous rodent osteoblast cell line (ATCCTMNPO CRL-2836 at four different concentrations (0.1, 1.0, 10.0, and 100.0 μg/mL of ligand CD80 alone, VEGF antibody alone, and a combination thereof (CD80+VEGF. Systems were implemented every 24 h over different sequential treatment timelines: 24, 48, and 72 h, to find the optimal protein concentration required for a reduction in cell proliferation. Results demonstrated that a combination of ligand CD80 and VEGF antibody was consistently most effective at reducing aberrant osteoblastic proliferation for both the 24- and 72-h timelines. At 48 h, however, an increase in cell proliferation was documented for the 0.1 and 1 μg/mL groups. For the 24- and 72-h tests, concentrations of 1.0 μg/mL of CD80+VEGF and 0.1 μg/mL of VEGF antibody were most effective. Concentrations of 10.0 and 100.0 μg/mL of CD80+VEGF reduced cell proliferation, but not as remarkably as the 1.0 μg/mL concentration. In addition, cell proliferation data showed that multiple treatments (72-h test induced cell death in the osteoblasts better than a single treatment. Future targeted drug delivery system research includes trials in OSA cell lines from greater phylum

  7. 儿童烧伤创面感染细菌种类分布及耐药情况%INVESTIGATION OF BACTERIAL SPECIES DISTRIBUTION AND DRUG RESISTANCE OF CHILDREN WITH BURN WOUND INFECTION

    Institute of Scientific and Technical Information of China (English)

    戴昆琦; 奕利娟; 陈群英

    2012-01-01

    目的 研究医院病房儿童烧(烫)伤患者创面感染细菌分布和耐药情况.方法 采用细菌分离培养和药敏试验方法,对住院儿童烧伤创面分泌物标本进行了检测.结果 从1 698份标本中检出致病菌379株,检出率为22.32%.烧伤感染致病菌中,革兰阳性球菌占65.17%,革兰阴性杆菌占32.98%,真菌占1.85%.检出的铜绿假单胞菌对氨苄西林、头孢曲松、复方新诺明耐药率均高达100%,鲍曼不动杆菌对氨曲南、环丙沙星和复方新诺明耐药率均高达80%以上.结论 该医院住院儿童烧伤感染致病菌以革兰阳性球菌为主,但革兰阴性杆菌耐药率高.%Objective To investigate the bacterial species distribution and drug resistance of children with bum wound infection. Methods The bacteria isolated culturing and the medicine sensitive test were used to detect secretion specimen from burn wound of children. Results From 1 698 specimen there were 379 strains pathogenic bacteria detected and the positive rate was 22. 32%. Of the burn infection pathogenic bacteria the gram positive coccus accounted for 63. 17% , the gram negative bacillus accounted for 32. 98% and the fungus accounted for 1.85%. The resistance rates of Pseudomonas aeruginosa detected to Amicillin, Ceftriaxone, Trimethoprim - sulfamethoxazole reached 100% , while the resistance rates of Acinetobacter buumannii detected to Aztreonam, Ciprofloxacin and Trimethoprim - sulfamethoxazole were above 80%. Conclusion The main infection pathogenic bacteria of children bum wound are the gram positive coccus and the drug resistance rate of negative bacillus is high.

  8. The Role of the Entertainment Industry in Deglamorizing Drug Use. Hearing before the Permanent Subcommittee on Investigations of the Committee on Governmental Affairs. United States Senate, Ninety-Ninth Congress, First Session.

    Science.gov (United States)

    Congress of the U.S., Washington, DC. Senate Committee on Governmental Affairs.

    The text of a Senate hearing is presented in this document. In opening remarks, Senators William Roth and Sam Nunn discuss the serious nature of the problem of drug abuse and the crime it fosters. Margaret Heckler, Secretary of the Department of Health and Human Services gives testimony on the statistics of drug abuse, the activities of the…

  9. 21 CFR 812.45 - Informing investigators.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Informing investigators. 812.45 Section 812.45 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... investigational plan and the report of prior investigations of the device....

  10. Antineoplastic Drugs.

    Science.gov (United States)

    Morris, Sara; Michael, Nancy, Ed.

    This module on antineoplastic drugs is intended for use in inservice or continuing education programs for persons who administer medications in long-term care facilities. Instructor information, including teaching suggestions, and a listing of recommended audiovisual materials and their sources appear first. The module goal and objectives are then…

  11. Drug Facts

    Medline Plus

    Full Text Available ... Phone Numbers and Websites Search Share Listen English Español Information about this page Click on the button ... sobre el abuso de drogas, y adicción. English Español About the National Institute on Drug Abuse (NIDA) | ...

  12. Mucoactive drugs

    Directory of Open Access Journals (Sweden)

    R. Balsamo

    2010-06-01

    Full Text Available Mucus hypersecretion is a clinical feature of severe respiratory diseases such as asthma, cystic fibrosis and chronic obstructive pulmonary disease. Airway mucosal infection and/or inflammation associated with these diseases often gives rise to inflammatory products, including neutrophil-derived DNA and filamentous actin, in addition to bacteria, apoptotic cells and cellular debris, that may collectively increase mucus production and viscosity. Mucoactive agents have been the medication of choice for the treatment of respiratory diseases in which mucus hypersecretion is a clinical complication. The main purpose of mucoactive drugs is to increase the ability to expectorate sputum and/or decrease mucus hypersecretion. Many mucoactive drugs are currently available and can be classified according to their putative mechanism of action. Mucoactive medications include expectorants, mucoregulators, mucolytics and mucokinetics. By developing our understanding of the specific effects of mucoactive agents, we may result in improved therapeutic use of these drugs. The present review provides a summary of the most clinically relevant mucoactive drugs in addition to their potential mechanism of action.

  13. Drug Facts

    Medline Plus

    Full Text Available ... Prevention Phone Numbers and Websites Search Share Listen English Español Information about this page Click on the ... información sobre el abuso de drogas, y adicción. English Español About the National Institute on Drug Abuse ( ...

  14. Drug resistance

    NARCIS (Netherlands)

    Gorter, J.A.; Potschka, H.; Noebels, J.L.; Avoli, M.; Rogawski, M.A.; Olsen, R.W.; Delgado-Escueta, A.V.

    2012-01-01

    Drug resistance remains to be one of the major challenges in epilepsy therapy. Identification of factors that contribute to therapeutic failure is crucial for future development of novel therapeutic strategies for difficult-to-treat epilepsies. Several clinical studies have shown that high seizure f

  15. 我国部分省区牛源金黄色葡萄球菌抗菌药物敏感性调查%The Investigation of the Drug Resistance of Staphylococcus Aureus Isolated from Bovine Mastitis in China

    Institute of Scientific and Technical Information of China (English)

    王登峰; 李建军; 高攀; 吴建勇; 杨学云; 韩博; 王治才

    2013-01-01

    were investigated by disc diffusion method. The results showed that the strains were sensitive or intermediary to cefoxitin, doxycycline and tetracycline, resistance to erythromycin, clindamycin, penicillin, sulfamethoxazole compound, and heterogeneous to chloramphenicol, ciprofloxacin and gentamicin according to area of origin. Analysis of the multi-drug resistance situation, 66%~100% strains resisted to at least 3 antibiotics, more than 70% Beijing strains resisted to almost 5 antibiotics. In addition, 86 Xinjiang and 20 Zhejiang strains isolated after 2009 all resisted to erythromycin, clindamycin, penicillin, sulfamethoxazole compound, doxycycline and tetracycline, and most strains resisted to chloramphenicol, ciprofloxacin and gentamicin, furthermore, cefoxitin-resistance strains has arisen. Regarding the situation of multi-drug resistance, more than 86% the strains resisted to more than 5 antibiotics, and the situation was more serious than the strains of Beijing, Shanxi province and Inner Mongolia Autonomous Region. The investigation of antimicrobial sensitive of bovine Staphylococcus aureus isolated from five areas of China suggested that all the strains resisted to some types antibiotics besides cephalosporins and almost all strains resisted to macrolide antibiotics(erythromycin), Lincosamides(clindamycin), Penicillin (penicillin) and sulfa antibiotics(sulfamethoxazole compound), and at the same time, most strains resisted to 3 to 5 types antibiotics. More important was that cefoxitin-resistance Staphylococcus aureus(Meticillin-resistant Staphylococcus aureus, MRSA) had emerged in Xinjiang and Zhejiang. The investigation suggested that multi-drug resistance Staphylococcus aureus would be a trouble to veterinarian and cause serious loss in dairy farm, and the survey will improve rational use of antibiotics in cow mastitis treatment.

  16. Spectroscopic and nano-molecular modeling investigation on the binary and ternary bindings of colchicine and lomefloxacin to Human serum albumin with the viewpoint of multi-drug therapy

    Energy Technology Data Exchange (ETDEWEB)

    Chamani, J., E-mail: Chamani@ibb.ut.ac.i [Department of Biology, Faculty of Sciences, Islamic Azad University-Mashhad Branch, Mashhad (Iran, Islamic Republic of); Asoodeh, A. [Department of Chemistry, Faculty of Sciences, Ferdowsi University of Mashhad, Mashhad (Iran, Islamic Republic of); Homayoni-Tabrizi, M. [Department of Biology, Faculty of Sciences, Islamic Azad University-Mashhad Branch, Mashhad (Iran, Islamic Republic of); Amiri Tehranizadeh, Z.; Baratian, A.; Saberi, M.R. [Medical Chemistry Department, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad (Iran, Islamic Republic of); Gharanfoli, M. [Department of Development Biology, Culture and Science University, Tehran (Iran, Islamic Republic of)

    2010-12-15

    Combination of several drugs is often necessary especially during long-term therapy. The competitive binding drugs can cause a decrease in the amount of drug bound to protein and increase the biological active fraction of the drug. The aim of this study is to analyze the interactions of Lomefloxacin (LMF) and Colchicine (COL) with human serum albumin (HSA) and to evaluate the mechanism of simultaneous binding of LMF and COL to protein. Fluorescence analysis was used to estimate the effect of drugs on the protein fluorescence and to define the binding and quenching properties of drugs-HSA complexes. The binding sites for LMF and COL were identified in tertiary structure of HSA with the use of spectrofluorescence analysis. The analysis of fluorescence quenching of HSA in the binary and ternary systems show that LMF does not affect the complex formed between COL and HSA. On the contrary, COL decreases the interaction between LMF and HSA. The results of synchronous fluorescence, resonance light scattering and circular dichroism spectra of binary and ternary systems show that binding of LMF and COL to HSA can induce micro-environmental and conformational changes in HSA. The simultaneous presence of LMF and COL in binding to HSA should be taken into account in the multi-drug therapy, and necessity of using a monitoring therapy owning to the possible increase of the uncontrolled toxic effects. Molecular modeling of the possible binding sites of LMF and COL in binary and ternary systems to HSA confirms the spectroscopic results.

  17. [Chirality and drugs].

    Science.gov (United States)

    Testa, B; Reist, M; Carrupt, P A

    2000-07-01

    The two enantiomers of a chiral drug may have vastly different pharmacodynamic and pharmacokinetic properties. As a result, the research and development of chiral drugs raises specific problems some of which are discussed here. Thus, various pharmacokinetic interactions may involve two enantiomers, as seen for example when one enantiomer inhibits the metabolism of the other and modifies its effects. A different situation occurs when a third compound stereoselectively inhibits the metabolism of one of the two enantiomers. Another problem examined here results from the lack of configurational stability of some chiral drugs, a little known phenomenon whose consequences can be of pharmacological or pharmaceutical significance depending on the rate of the reaction of racemization or epimerisation. In-depth investigations are needed before choosing between a eutomer or a racemate.

  18. Investigation and Analysis of the Use of Animal Drugs on the Medium-size and Small Pig Farms in Shandong Area%山东地区中小型猪场兽药使用情况调查与分析

    Institute of Scientific and Technical Information of China (English)

    张慧; 邹明; 张启迪

    2013-01-01

    In order to improve professional knowledge of pig-raising farmers and strengthen the rational use of veterinary drugs and monitoring of the drug residues, we investigated the basic information of medium-size and small pig farms and the use of veterinary drugs in the process of breeding in Shandong area through a variety of ways. Findings indicated that preventing drugs currently used on pig farms were mainly antibacterial drugs, Chinese traditional medicines, antiparasitic drugs, nutrient and antiviral drugs, and the remedial drugs used were mainly Chinese traditional medicines, antiviral drugs and antiparasitic drugs. Chinese traditional medicines were mainly for improving the body immunity and preventing virus diseases. Parasitic diseases were primarily based on prevention. During the investigation, some inhibitory drugs have been found still in use on some farms, so we should strengthen the supervision.%  为提高养殖户专业知识水平、加强合理用药及兽药残留的监控,通过多种途径调查山东地区中小型猪场基本信息及养殖过程中兽药使用情况。调查结果表明:目前山东地区使用的预防性兽药大类主要有抗菌药、中药、抗寄生虫药、营养药物、抗病毒药等,使用的治疗性兽药大类主要是抗菌药、中药、抗病毒药、抗寄生虫药等;中药主要用来提高机体免疫力、预防病毒病;寄生虫病主要以预防为主。调查中发现部分猪场有使用禁用兽药的现象,应加强监管。

  19. Optimal drug use and rational drug policy.

    Science.gov (United States)

    Miller, Geoffrey F

    2011-12-01

    The Müller & Schumann (M&S) view of drug use is courageous and compelling, with radical implications for drug policy and research. It implies that most nations prohibit most drugs that could promote happiness, social capital, and economic growth; that most individuals underuse rather than overuse drugs; and that behavioral scientists could use drugs more effectively in generating hypotheses and collaborating empathically.

  20. 某二级医院基本药物使用情况调查分析%Investigation and Survey of Essential Drug Used in a Second-grade Hospital

    Institute of Scientific and Technical Information of China (English)

    丁立云

    2014-01-01

    Objective To master the utilization of national essential drugs in a hospital in 2013 in order to provide reference for rational use of essential drugs. Methods The utilization of national essential drugs in a hospital in 2013 was analyzed statistically using the Pharmacy management of Hospital Information System. Results 328 kinds of national essential drugs were adopted in a hospital,which accounted for 40.44%of national essential drugs. The consumption sum of national essential drugs accounted for 29.52%of total annual consumption sum of drugs. Conclusion The coverage rate and utilization rate of national essential drugs in a hospital should be further improved,but this list is not able to meet the demand of second-grade hospitals,especially in developed area. The non-national essential drugs play a major determinant and more effective role in the control of the total drug expenditure.%目的:调查分析某二级医院2013年基本药物使用情况,为进一步提高基本药物在该院的使用效果提供参考。方法收集整理2013年1月~2013年12月该院门诊和住院基本药物的使用品规数、销售金额等,采用办公软件Excel2003对数据进行处理。结果该院实施基本药物制度后,使用基本药物品规数328种占全部药物品规数的40.44%,基本药物品种使用金额比率为29.52%。结论实施基本药物制度,减轻患者的经济负担,维护患者的利益,该院使用基本药物的比率仍较低,需进一步提高和改进。国家基本药物目录仍无法满足二级医院的医疗需求,特别是经济较发达地区。非基本药物是药品费用的主要决定因素,降低非基本药物价格能有效降低药品费用。

  1. FTA法与FMECA法在药品质量偏差调查中的应用%Application of FTA Method and FMECA Method in Drug Quality Deviation Investigation

    Institute of Scientific and Technical Information of China (English)

    谭宏宇; 单华峰; 李天翥; 王宇; 陈景超

    2016-01-01

    OBJECTIVE:To provide new idea and method for the prevention and control of drug quality risk in pharmaceutical enterprises in China. METHODS:Taking the deviation investigation of pyrogen test for a TCM injection produced by a pharmaceu-tical enterprise in Apr. 2014 as an example. Influential factors (including staff,machine,material,method,environment) which could induce the deviation were analyzed by Fault tree analysis (FTA) method and Failure mode,effects and criticality analysis (FMECA) method. Both systematic drug quality deviation investigation and risk assessment model were established. RESULTS &CONCLUSIONS:The direct reason for deviation of pyrogen test is that the experimental interval does not conform to require-ments;root reason is that cost saving of laboratory leads to insufficient quantity of rabbits(i.e. there are loopholes in the manage-ment system of material element). In addition,it is found that preparation and injection process of test solution lack of check and have poor traceability;preparation process has pyrogen and concentration error risk,and injection process has operating errors risk (i.e. there are loopholes in the element management system). By revising Laboratory Animal Purchase and Management System, strengthening training and improving monitoring mechanism,adding recheck and video monitoring for preparation and injection steps of test solution by two persons,revising related documents and records,and other measures,this kind of deviation,which are caused by material not meeting the requirements,are effectively prevented from happening again. And,such deviations,which are caused by absence of recheck and other necessary operations in the process of inspection,are also effectively prevented from hap-pening again. FMECA and FTA can effectively enhance the directionality of deviation investigation so as to improve the systematic and scientific property of investigation process. This mode has practical value.%目的:为我国制药企

  2. Investigation of drug use of hospitalized patients with mental disorder for 3 years%医院2011-2013年精神障碍住院患者用药情况

    Institute of Scientific and Technical Information of China (English)

    程呈斌; 陈剑华

    2013-01-01

    Objective To observe the alteration of clinical application of psychotropic drug therapy in recent three years.Methods We used one day time point survey to investigate pharmacotherapy status of 1371 inpatient mental disorder patients at Shanghai Mental Health Center(Minhang campus).Results ① The use of typical antipsychotics was stable; among atypical antipsychotics,the use of risperidone was decreased from 21.1% in 2011 to 17.1% in 2013,while the use of aripiprazole was increased from 11.2% in 2011 to 14.9% in 2013.② Selective serotonin reuptake inhibitors(SSRI) was still the first choice among antidepressant agents(61.5%),while the new antidepressant mirtazapine dosage was increased year by year.③ Zopiclone became the top-rank medicine among the sedative-hypnotic.Conclusions The use of new drugs is increasing year by year.Diversity and safety have now become the trend in the selection of antipsychotics.%目的 分析2011-2013年精神障碍住院患者精神药物的使用情况及临床用药情况.方法 采用一日法对上海交通大学医学院附属精神卫生中心闵行院区2013年4月1日住院精神障碍患者1371例的精神药物应用状况进行调查,并与2012年4月1日和2011年4月1日的数据进行比较.结果 ①典型抗精神病药用量稳定,非典型抗精神病药中利培酮使用频率由2011年的21.1%降到至2013年的17.1%,而阿立派唑由2011年的11.2%升到至2013年的14.9%.②选择性5羟色胺再摄取抑制剂(SSRI)仍占据抗抑郁剂首位(61.5%),而新型抗抑郁剂米氮平用量逐年上升.③佐匹克隆在镇静催眠药使用中排名第一.结论 新型药物临床应用比例正逐年上升,多样性、安全性已成为目前精神疾病临床用药的趋势.

  3. 某医院儿科抗菌药物使用情况调查及分析%Investigation of pediatric medical records and analysis of antimicrobial drug application in a certain hospital

    Institute of Scientific and Technical Information of China (English)

    伍明初; 陈育光; 吴秀廉

    2014-01-01

    Objective To investigate the application of antibacterials in clinical pediatry , so as to provide evidence for ration-al application of antimicrobials clinically .Methods Two hundred and forty filed medical records from pediatric patients discharged from the hospital in 2012 were selected and analyzed .The medical data included gender , age, length of hospital stay , diagnosis upon admission and discharge , the application of antibiotics , compatibility and combination of drugs , microbial laboratory detection etc . Results (1) Respiratory diseases were the most common disorders among the pediatric patients , accounting for 31.18%, and were followed by nervous system diseases , accounting for 18.63%.(2) The application rate of antibacterials among the 227 pediatric pa-tients was 94.58%, and the percentage of antibacterial drug combination accounted for 56.83%.(3) The rate of microbial laboratory detection was 17.18%, and of the 52 samples sent for laboratory detection , 16 samples had pathogenic bacteria growth (30.77%). Conclusion Irrational use of antibacterials in the pediatric department of the hospital was quite common , which remained to be rectified .%目的:调查儿科临床抗菌药物使用情况,为临床合理使用抗菌药物提供参考。方法抽取某医院儿科2012年出院归档病历240份进行分析,内容包括患儿性别、年龄、住院时间、入(出)院诊断及转归,抗菌药物的用法、配伍、联合用药、微生物送检等情况。结果(1)本组患儿以呼吸系统疾病最多,占31.18%,神经系统疾病次之,占18.63%;(2)227例患儿使用了抗菌药物,使用率94.58%,抗菌药物联用比例占56.83%;(3)微生物检验样本送检率17.18%,送检的52份标本中16份有致病菌生长(30.77%)。结论该院儿科临床滥用、乱用抗菌药物的现象较普遍,有待进一步规范管理。

  4. Investigation of drug consumption with ABC analysis in our hospital in the first quarter of 2011%应用ABC分析法调查我院2011年第一季度药物消耗情况

    Institute of Scientific and Technical Information of China (English)

    徐艳敏; 李倩; 刘燕娟; 张洪峰

    2012-01-01

    目的 了解我院2011年第一季度药物使用情况,分析用药状况及用药趋势,对我院药房进行科学有效的管理,有效利用医疗资源,促进临床合理用药.方法 采用ABC分析法对药品使用数量、销售金额和品种数进行统计分析,并重点对A类药品进行药物学分类及用药分析.结果 统计药品共1 026种,其中A类药品共167种,占药品百分比为16.28%,金额53 647 730元,百分比为74.25%;B类药品共137种,占药品百分比为13.35%,金额12 074 116元,百分比为16.71%;C类药品共722种,占药品百分比为70.37%,金额6 535 319元,百分比为9.04%.其中A类药品主要集中在抗微生物和神经系统用药.结论 本院抗生素药存在使用不合理的情况,应加强抗生素类药品管理.%Objective To comprehend drug use and analyze situation and trends of drug use in our hospital in the first quarter of 2011, in order to manage our pharmacy scientifically and effectively, use medical resources effectively, and promote the rational drug use in clinical practice. Methods The ABC analysis was used to statistical analyze quantity, sales amount and variety of drugs used, with emphasis on pharmacology classification and drug use of class A drugs. Results 1 026 kinds of drugs were counted, including 167 kinds of class A drugs which accounted for 16.28%, and the expense amounted to 53 647 730 yuan which accounted for 74.25%. Class B drugs were 137 species, accounting for drug percentage of 13.35%, the expense amounted to 12 074 116 yuan which accounted for 16.71%. Class C drugs were 722 species, accounting for drug percentage of 70.37%, the expense amounted to 6 535 319 yuan which accounted for 9.04%. And class A drugs mainly concentrated in anti-microbial and nervous system drugs. Conclusion Antibiotics exists unreasonable using conditions sometimes in our hospital, so it is necessary to strengthen the management of antibiotics.

  5. [Emergent drugs (I): smart drugs].

    Science.gov (United States)

    Burillo-Putze, G; Díaz, B Climent; Pazos, J L Echarte; Mas, P Munné; Miró, O; Puiguriguer, J; Dargan, P

    2011-01-01

    In recent years, a series of new drugs, known as smart drugs or legal highs, have gaining in popularity. They are easily obtainable through online shops. This is happening amongst younger segments of the population and is associated with recreational consumption, at weekends. In general, they are synthetic derivatives of natural products. There has been hardly any clinical research into them and they are not detectable in hospital laboratories. Three of these products, BZP (1- benzylpiperazine), mefedrone (4-methylmethcathinone) and Spice are probably the most widely used in Europe. The first two are consumed as an alternative to ecstasy and cocaine and are characterized by their producing a clinical profile of a sympathetic mimetic type; on occasion, they have serious consequences, with convulsions and even death. Spice (a mixture of herbs with synthetic cannabinoids such as JWH-018, JWH-073 and CP 47497-C8) is giving rise to profiles of dependence and schizophrenia. Although the emergent drugs have an aura of safety, there is an increasing amount of experience on their secondary effects.

  6. Carbohydrate drugs: current status and development prospect.

    Science.gov (United States)

    Zhang, Yan; Wang, Fengshan

    2015-04-01

    In recent years, there has been a great effort devoted to the investigation of the roles of carbohydrates in various essential biological processes and the development of carbohydrates to therapeutic drugs. This review summarizes the carbohydrate drugs which have been recorded in several pharmacopoeias, marketed, and under development. A prospect of the future development of carbohydrate drugs is discussed as well.

  7. The potential drug-drug interaction between proton pump inhibitors and warfarin

    DEFF Research Database (Denmark)

    Henriksen, Daniel Pilsgaard; Stage, Tore Bjerregaard; Hansen, Morten Rix

    2015-01-01

    BACKGROUND: Proton pump inhibitors (PPIs) have been suggested to increase the effect of warfarin, and clinical guidelines recommend careful monitoring of international normalized ratio (INR) when initiating PPI among warfarin users. However, this drug-drug interaction is sparsely investigated...

  8. Drug resistance and antiretroviral drug development

    OpenAIRE

    Shafer, Robert W.; Jonathan M Schapiro

    2005-01-01

    As more drugs for treating HIV have become available, drug resistance profiles within antiretroviral drug classes have become increasingly important for researchers developing new drugs and for clinicians integrating new drugs into their clinical practice. In vitro passage experiments and comprehensive phenotypic susceptibility testing are used for the pre-clinical evaluation of drug resistance. Clinical studies are required, however, to delineate the full spectrum of mutations responsible fo...

  9. High throughput drug profiling

    OpenAIRE

    Entzeroth, Michael; Chapelain, Béatrice; Guilbert, Jacques; Hamon, Valérie

    2000-01-01

    High throughput screening has significantly contributed to advances in drug discovery. The great increase in the number of samples screened has been accompanied by increases in costs and in the data required for the investigated compounds. High throughput profiling addresses the issues of compound selectivity and specificity. It combines conventional screening with data mining technologies to give a full set of data, enabling development candidates to be more fully compared.

  10. Botanicals as "new" drugs: US development.

    Science.gov (United States)

    Hoffman, Freddie Ann

    2015-11-01

    Botanicals are ingredients that can be marketed as foods, drugs, cosmetics, and medical devices in the United States. When a botanical is intended to diagnose, treat, prevent, mitigate, or cure a disease, it is considered to be a "drug". This article reviews the US regulatory requirements for botanicals as "new" drugs. An overview of the regulatory principles used to determine product category and the basic elements of an Investigational New Drug application and New Drug Application with the US Food and Drug Administration are presented. This article is part of a Special Issue entitled "Botanicals for Epilepsy".

  11. Investigation on Antimicrobial Drug Resistance to Escherichia coli Isolates from A Farm in Tacheng Xinj iang%新疆塔城某规模化养殖场大肠埃希菌耐药性调查

    Institute of Scientific and Technical Information of China (English)

    南海辰; 夏利宁; 刘英玉; 翟少华; 底丽娜

    2014-01-01

    为了解新疆塔城某规模化养殖场分离的大肠埃希菌对临床常用抗菌药物的耐药情况,从该规模化养殖场中采集的水样、饲料样、牛粪样及羊粪样中分离大肠埃希菌。采用微量肉汤法检测其对抗菌药物的耐药情况。结果表明,采集牛源饮用水样35份,分离率100.0%(35/35),分离的大肠埃希菌仅对阿莫西林/克拉维酸(31.4%)和氨苄西林(20.0%)2种抗菌药物耐药;牛源饲料样15份,分离率86.7%(13/15),分离的大肠埃希菌对氨苄西林(30.8%)、阿莫西林/克拉维酸(23.1%)、安普霉素(15.4%)、诺氟沙星(7.7%)、恩诺沙星(7.7%)和庆大霉素(7.7%)6种抗菌药物耐药;牛粪样20份,分离率100.0%(20/20),分离的大肠埃希菌对氨苄西林(60.0%)、阿莫西林/克拉维酸(50.0%)、恩诺沙星(40.0%)、庆大霉素(40.0%)、头孢噻呋(35.0%)、阿米卡星(25.0%)、诺氟沙星(10.0%)和环丙沙星(10.0%)8种抗菌药物耐药;羊粪样55份,分离率100.0%(55/55),分离的大肠埃希菌对阿莫西林/克拉维酸(25.5%)、氨苄西林(12.7%)、庆大霉素(5.5%)、头孢噻呋(3.6%)、诺氟沙星(1.8%)、恩诺沙星(1.8%)和阿米卡星(1.8%)7种抗菌药物耐药。新疆塔城牛源大肠埃希菌对常用抗菌药物多药耐药情况较严重,临床用药需谨慎,且可能存在粪源菌污染水源和饲料的风险。%In order to investigate commonly used antimicrobial drug resistance to Escherichia coli isolates from a farm in Tacheng,Xinj iang,the minimal inhibitory concentrations (MIC)of the antimicrobial drugs to these isolates from drinking water,feed,bovine feces and ovine feces were determined by the broth mi-cro-dilution method.The results showed that:3 5 E.coli isolates were confirmed

  12. Drug delivery systems from nose to brain.

    Science.gov (United States)

    Misra, Ambikanandan; Kher, Gitanjali

    2012-09-01

    The treatment of brain disorders is particularly challenging due to the presence of a variety of formidable obstacles to deliver drugs selectively and effectively to the brain. Blood-brain-barrier (BBB) constitutes the major obstacle to the uptake of drugs into the brain following systemic administration. Intranasal delivery offers a non-invasive and convenient method to bypass the BBB and delivery of therapeutics directly to the brain. The review discusses the potential of intranasal route to deliver drugs to the brain, the mechanisms and pathways of direct nose to brain drug transport, the various factors influencing transnasal drug absorption, the conventional and novel intranasal drug delivery systems, the various intranasal drug delivery techniques and devices, and examples of brain drug transport that have been feasible in treating various brain disorders. Moreover, products on the market, investigational drugs, and the author's perceptions about the prospect of intranasal delivery for treating brain disorders are also been discussed.

  13. An investigation into the use of polymer blends to improve the printability of and regulate drug release from pharmaceutical solid dispersions prepared via fused deposition modeling (FDM) 3D printing.

    Science.gov (United States)

    Alhijjaj, Muqdad; Belton, Peter; Qi, Sheng

    2016-11-01

    FDM 3D printing has been recently attracted increasing research efforts towards the production of personalized solid oral formulations. However, commercially available FDM printers are extremely limited with regards to the materials that can be processed to few types of thermoplastic polymers, which often may not be pharmaceutically approved materials nor ideal for optimizing dosage form performance of poor soluble compounds. This study explored the use of polymer blends as a formulation strategy to overcome this processability issue and to provide adjustable drug release rates from the printed dispersions. Solid dispersions of felodipine, the model drug, were successfully fabricated using FDM 3D printing with polymer blends of PEG, PEO and Tween 80 with either Eudragit E PO or Soluplus. As PVA is one of most widely used polymers in FDM 3D printing, a PVA based solid dispersion was used as a benchmark to compare the polymer blend systems to in terms of processability. The polymer blends exhibited excellent printability and were suitable for processing using a commercially available FDM 3D printer. With 10% drug loading, all characterization data indicated that the model drug was molecularly dispersed in the matrices. During in vitro dissolution testing, it was clear that the disintegration behavior of the formulations significantly influenced the rates of drug release. Eudragit EPO based blend dispersions showed bulk disintegration; whereas the Soluplus based blends showed the 'peeling' style disintegration of strip-by-strip. The results indicated that interplay of the miscibility between excipients in the blends, the solubility of the materials in the dissolution media and the degree of fusion between the printed strips during FDM process can be used to manipulate the drug release rate of the dispersions. This brings new insight into the design principles of controlled release formulations using FDM 3D printing. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Drug Coverage (Part D)

    Science.gov (United States)

    ... insurance Find health & drug plans Drug coverage (Part D) How to get drug coverage Get Medicare prescription drug coverage either from a Part D plan or a Medicare Advantage Plan offering Medicare ...

  15. National Drug Code Directory

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Drug Listing Act of 1972 requires registered drug establishments to provide the Food and Drug Administration (FDA) with a current list of all drugs...

  16. National Drug Code Directory

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Drug Listing Act of 1972 requires registered drug establishments to provide the Food and Drug Administration (FDA) with a current list of all drugs manufactured,...

  17. Prescription Drug Abuse

    Science.gov (United States)

    ... over-the-counter medications. National Institute on Drug Abuse. http://www.drugabuse.gov/publications/drugfacts/prescription-over-counter- ... 2015. Prescription drug abuse. National Institute on Drug Abuse. http://www.drugabuse.gov/publications/research-reports/prescription-drugs/ ...

  18. Drugs Approved for Leukemia

    Science.gov (United States)

    This page lists cancer drugs approved by the FDA for use in leukemia. The drug names link to NCI's Cancer Drug Information summaries. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters.

  19. Drugs Approved for Retinoblastoma

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for retinoblastoma. The list includes generic names and brand names. The drug names link to NCI’s Cancer Drug Information summaries.

  20. Drugs Approved for Neuroblastoma

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for neuroblastoma. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  1. Urine drug screen

    Science.gov (United States)

    Drug screen -- urine ... detect the presence of illegal and some prescription drugs in your urine. Their presence indicates that you recently used these drugs. Some drugs may remain in your system for ...

  2. Medication/Drug Allergy

    Science.gov (United States)

    ... Science Education & Training Home Conditions Medication/Drug Allergy Medication/Drug Allergy Make an Appointment Find a Doctor ... immediate or delayed. What Is an Allergy to Medication/Drugs? Allergies to drugs/medications are complicated, because ...

  3. Amorphous drugs and dosage forms

    DEFF Research Database (Denmark)

    Grohganz, Holger; Löbmann, K.; Priemel, P.

    2013-01-01

    The transformation to an amorphous form is one of the most promising approaches to address the low solubility of drug compounds, the latter being an increasing challenge in the development of new drug candidates. However, amorphous forms are high energy solids and tend to recry stallize. New...... formulation principles are needed to ensure the stability of amorphous drug forms. The formation of solid dispersions is still the most investigated approach, but additional approaches are desirable to overcome the shortcomings of solid dispersions. Spatial separation by either coating or the use of micro......-containers has shown potential to prevent or delay recrystallization. Another recent approach is the formation of co-amorphous mixtures between either two drugs or one drug and one low molecular weight excipient. Molecular interactions between the two molecules provide an energy barrier that has to be overcome...

  4. Bioresponsive matrices in drug delivery

    Directory of Open Access Journals (Sweden)

    Ye George JC

    2010-11-01

    Full Text Available Abstract For years, the field of drug delivery has focused on (1 controlling the release of a therapeutic and (2 targeting the therapeutic to a specific cell type. These research endeavors have concentrated mainly on the development of new degradable polymers and molecule-labeled drug delivery vehicles. Recent interest in biomaterials that respond to their environment have opened new methods to trigger the release of drugs and localize the therapeutic within a particular site. These novel biomaterials, usually termed "smart" or "intelligent", are able to deliver a therapeutic agent based on either environmental cues or a remote stimulus. Stimuli-responsive materials could potentially elicit a therapeutically effective dose without adverse side effects. Polymers responding to different stimuli, such as pH, light, temperature, ultrasound, magnetism, or biomolecules have been investigated as potential drug delivery vehicles. This review describes the most recent advances in "smart" drug delivery systems that respond to one or multiple stimuli.

  5. Drug-mineral interactions

    Energy Technology Data Exchange (ETDEWEB)

    Kramer, L.

    1986-03-01

    The effect of drugs such as glucocorticoids and thyroid extract on calcium metabolism is unknown. However, several other medications affect the excretion and intestinal absorption of calcium. A controlled study was carried out to investigate these aspects. Urinary calcium was determined for 3 months during the long-term intake of the antituberculous drug isoniazid (INH) and of the antibiotic tetracycline. The effect of the diuretics furosemide and hydrochlorothiazide, of several aluminum-containing antacids, of thyroid extract and of corticosteroids was also studied. Metabolic balances of calcium, phosphorus, magnesium and zinc were determined, as well as the intestinal absorption of calcium using Ca 47. Plasma levels, urinary and fecal excretions of Ca 47 were determined. All drugs tested increased urinary calcium except for the diuretic hydrochlorothiazide. Regarding the effect of corticosteroids: the intestinal absorption of calcium was unchanged after the short-term use and was very high after long-term use. The studies have shown that several commonly used drugs induce an increase in urinary calcium excretion which may contribute to calcium loss, if this increase persists for prolonged periods of time. Urinary excretions of phosphorus, magnesium and zinc increased in some of the studies.

  6. 我院住院患儿超说明书用药情况调查%Investigation on Off-label Drug Use in Hospitalized Children of Our Hospital

    Institute of Scientific and Technical Information of China (English)

    陶兴茹; 裴保方; 段彦彦; 刘晓玲; 陈海燕; 曹松山

    2015-01-01

    OBJECTIVE:To provide baseline data for the formulation of the strategy for medical institutions in China. METH-ODS:3 600 discharged medical records were randomly collected from our hospital in 2013. According to drug package inserts,the judgment was carried out about whether off-label drug use existed in medical orders. The types of off-label drug use,off-label drug use of children in different age groups and of various drugs were all analyzed. RESULTS:A total of 3 268 hospitalized children were includ-ed,and 35 523 medical orders were analyzed,involving 468 types. Based on children,medical orders and drug types,the incidence of off-label drug use were 91.34%,35.72%and 48.72%,respectively. The types of off-label drug use mainly included pediatric medica-tion information(74.21%), exceeding route of administration(8.12%)and overage(8.45%). The top 3 age groups with respect to the incidence of off-label drug use were adolescents(42.42%),neonate(37.97%)and infant(35.48%). Top 4 drugs of off-label use in the list of medical orders were anti-infective drugs(23.65%),electrolytic,drugs for acid-base balance and nutrition(12.21%), drugs for respiratory system(36.84%)and cardiovascular drugs(63.21%). CONCLUSIONS:The off-label drug use of hospitalized children is common in our hospital. It is urgent to develop related laws and regulations or guidelines to regulate off-label drug use in or-der to ensure the safety of pediatric drug use.%目的:为制定超说明书用药政策提供基线数据。方法:随机抽取我院2013年出院患儿病历3600份,依据药品说明书判断其用药医嘱是否超说明书,分析各超说明书用药类型、各年龄段儿童及各类药品超说明书用药情况。结果:共纳入住院患儿3268例,分析用药医嘱35523条,涉及药品468种。按患儿、用药医嘱与药品品种计,超说明书用药发生率分别为91.34%、35.72%和48.72%。超说明书用药类型主要包括使用未提及

  7. DrugCentral: online drug compendium.

    Science.gov (United States)

    Ursu, Oleg; Holmes, Jayme; Knockel, Jeffrey; Bologa, Cristian G; Yang, Jeremy J; Mathias, Stephen L; Nelson, Stuart J; Oprea, Tudor I

    2017-01-04

    DrugCentral (http://drugcentral.org) is an open-access online drug compendium. DrugCentral integrates structure, bioactivity, regulatory, pharmacologic actions and indications for active pharmaceutical ingredients approved by FDA and other regulatory agencies. Monitoring of regulatory agencies for new drugs approvals ensures the resource is up-to-date. DrugCentral integrates content for active ingredients with pharmaceutical formulations, indexing drugs and drug label annotations, complementing similar resources available online. Its complementarity with other online resources is facilitated by cross referencing to external resources. At the molecular level, DrugCentral bridges drug-target interactions with pharmacological action and indications. The integration with FDA drug labels enables text mining applications for drug adverse events and clinical trial information. Chemical structure overlap between DrugCentral and five online drug resources, and the overlap between DrugCentral FDA-approved drugs and their presence in four different chemical collections, are discussed. DrugCentral can be accessed via the web application or downloaded in relational database format. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  8. Drug Preferences of Multiple Drug Abusers.

    Science.gov (United States)

    Harford, Robert J.

    1978-01-01

    Examined drug preferences of a group of active multiple drug abusers referred for treatment. Nearly half the respondents preferred drugs other than type they most frequently used. Preferences were related to method of administration. Results suggest preference is one among several determinants of drug use. (Author/BEF)

  9. Density functional and molecular docking studies towards investigating the role of single-wall carbon nanotubes as nanocarrier for loading and delivery of pyrazinamide antitubercular drug onto pncA protein

    Science.gov (United States)

    Saikia, Nabanita; Rajkhowa, Sanchaita; Deka, Ramesh C.

    2013-03-01

    The potential biomedical application of carbon nanotubes (CNTs) pertinent to drug delivery is highly manifested considering the remarkable electronic and structural properties exhibited by CNT. To simulate the interaction of nanomaterials with biomolecular systems, we have performed density functional calculations on the interaction of pyrazinamide (PZA) drug with functionalized single-wall CNT ( fSWCNT) as a function of nanotube chirality and length using two different approaches of covalent functionalization, followed by docking simulation of fSWCNT with pncA protein. The functionalization of pristine SWCNT facilitates in enhancing the reactivity of the nanotubes and formation of such type of nanotube-drug conjugate is thermodynamically feasible. Docking studies predict the plausible binding mechanism and suggests that PZA loaded fSWCNT facilitates in the target specific binding of PZA within the protein following a lock and key mechanism. Interestingly, no major structural deformation in the protein was observed after binding with CNT and the interaction between ligand and receptor is mainly hydrophobic in nature. We anticipate that these findings may provide new routes towards the drug delivery mechanism by CNTs with long term practical implications in tuberculosis chemotherapy.

  10. 我院儿科门诊超说明书用药调查%Investigation of Off-label Drug Use in Pediatric Outpatient Department of Our Hospital

    Institute of Scientific and Technical Information of China (English)

    李亚昙; 阿衣古丽·玉努斯; 滕亮

    2015-01-01

    目的:为促进儿科安全合理用药提供基线数据。方法:采用分层随机抽样法,抽取新疆医科大学第二附属医院2014年3月-2015年2月期间的儿科门诊处方,依据药品说明书内容,判断是否存在超说明书用药行为,对超说明书用药类型、患儿不同年龄段及各类药品之间的关系进行分析。结果:共抽取儿科门诊处方2400张,分析处方用药记录5115条,涉及用药品种171种。按照处方数、用药记录数和用药品种数分别计算,超说明书用药发生率分别为:59.08%、40.87%、80.70%。超说明书用药类型主要包括:超给药频次(43.03%)、超给药剂量(29.55%)、超适应证(18.83%)。门诊处方超说明书用药发生率居前2位的年龄段为:婴儿(67.58%)、青少年(63.10%%)。超说明书用药发生率居前4位的药物种类为:外用药(55.56%)、神经系统用药(54.12%)、呼吸系统用药(48.95%)、营养类药物(48.09%)。结论:儿科门诊处方中超说明书用药现象较为普遍。%OBJECTIVE:To provide baseline data of safe and rational drug use in pediatrics. METHODS:The pediatrics outpatient prescriptions were randomly selected from pediatric department of The Second Affiliated Hospital of Xinjiang Medi-cal University during Mar. 2014-Feb. 2015. The behavior of off-label drug use was determined according to the content of drug instruction. The type of off-label drug use,the relationship of different age groups with various drugs were analyzed. RE-SULTS:A total of 2400 outpatient prescriptions were collected from pediatric department,5115 medication records were ana-lyzed,involving 171 kinds of drugs. By the number of prescriptions,medication records and drug types,the incidence of off-la-bel drug use were 59.08%,40.87% and 80.70%,respectively. The main categories of drug off-label use were off-label dosing frequency(43.03%),off-label dosage

  11. Investigations with spectroscopy, zeta potential and molecular modeling of the non-cooperative behaviour between cyclophosphamide hydrochloride and aspirin upon interaction with human serum albumin: binary and ternary systems from multi-drug therapy.

    Science.gov (United States)

    Omidvar, Zahra; Parivar, Kazem; Sanee, Hamideh; Amiri-Tehranizadeh, Zeinab; Baratian, Ali; Saberi, Mohammad Reza; Asoodeh, Ahmad; Chamani, Jamshidkhan

    2011-08-01

    The interaction between cyclophosphamide hydrochloride (CYC) and aspirin (ASA) with human serum albumin (HSA) was studied by various kind of spectroscopic, ζ potential and molecular modeling under physiological conditions. The fluorescence data showed that the binding of drugs to proteins caused strong static fluorescence quenching. The analysis of the fluorescence quenching of HSA in the binary and ternary systems displayed that ASA was affected by the complex formed between CYC and HSA. Moreover, CYC was influenced by the HSA-ASA complex. The inherent binding information, including the quenching mechanism, binding constants, number of binding sites, effective quenching constant, fraction of the initial fluorescence and thermodynamic parameters were measured by the fluorescence quenching technique at various temperatures. In addition, according to the synchronous fluorescence spectra of HSA, the results showed that the fluorescence quenching of HSA originated from the Trp and Tyr residues, and indicated a conformational change of HSA with the addition of the drugs. Far-UV CD spectra of HSA were recorded before and after the addition of ASA and CYC as binary and ternary systems. An increase in intensity of the positive CD peak of HSA was observed in the presence of the drugs. The results were interpreted by excited interactions between the aromatic residues of the HSA binding sites and the drugs bound to them. The distance r between donor and acceptor was obtained by the Forster energy according to fluorescence resonance energy transfer (FRET) and found to be 2.35 nm and 1.78 nm for CYC and ASA, respectively. This confirmed the existence of static quenching for proteins in the presence of CYC and ASA. Furthermore, docking studies pointed at a reduction of the affinity of each of the drug compounds to the protein in the presence of the other in meaningful amounts. Pre-binding of any of the said compounds forced the second to bind in a non-optimized location and

  12. Investigation and analysis of personnel in Dalian oral hygiene a drug addiction treatment center%大连市某戒毒所吸毒人员口腔卫生情况的调查及分析

    Institute of Scientific and Technical Information of China (English)

    孙晶; 白晓峰

    2014-01-01

    目的:了解某戒毒所吸毒人员口腔卫生状况。方法检查大连市某强制戒毒所正在戒毒人员的龋病及简化口腔卫生指数情况,分析患龋率,龋均,简化口腔卫生指数(牙石指数,软垢指数)与吸毒时间的关系。结果本次共调查吸毒人员201人,患龋率89.7%,龋均4.65。均高于普通人群,且吸毒时间大于两年的吸毒人员,其龋均明显高于吸毒时间小于两年的人员,P<0.05。简化口腔卫生指数未发现与吸烟时间的长短有关系。结论吸毒人群更易罹患龋病,吸毒时间与龋均升高有正相关的联系。%Objective To understand an addiction treatment center staff oral health drugs. Dalian, a way to check is compulsory detoxification and rehabilitation personnel caries simplified oral hygiene index, analyze the prevalence of dental caries, caries, simplify oral hygiene index (calculus index, debris index) the relationship between drug use of time. The results of this survey were 201 drug users, caries prevalence of 89.7%, DMFT 4.65. Were higher than the general population, and drug addicts for longer than two years, which were significantly higher caries drug in less than two persons, P <0.05. Simplified oral hygiene index was not found and the length of time a relationship of smoking among drug users more likely to suffer from dental caries conclusion, drug abuse has increased time and caries were positively related links.

  13. Investigation of prevention and response of clinicians to disputes of adverse drug reactions%临床医师防范和应对药品不良反应纠纷的调查分析

    Institute of Scientific and Technical Information of China (English)

    阎仲珩; 黄登笑; 黄淇敏

    2011-01-01

    Objective To investigate the prevention and response of clinicians to disputes of adverse drug reactions ( ADR), and explore effective ways for medical institutions to deal with disputes of ADR.Methods Questionnaire survey was conducted in 370 clinicians selected from 10 affiliated hospitals of Shanghai Jiaotong University School of Medicine.The questionnaires were composed of two sections.The basic conditions of clinicians were included in one section, and the other section was about a specific survey concerned with the basic concept of ADR, and the recognition and application of prevention measures and methods dealing with ADR disputes.Results A total of 361 questionnaires ( 97.57% ) were recovered, with 347 effective questionnaires (96.12%).Most clinicians were in favor of the commonly adopted prevention measures and methods dealing with ADR disputes.More than 60% of clinicians believed that all the prevention measures to ADR disputes were effective.For the methods dealing with ADR disputes, 37.5% of clinicians were for the measure of “waiving charges”, and more than 60% of clinicians approved the other methods dealing with ADR disputes.Conclusion At present, “standard reporting cases”, “referring to drug manual”, “notification before treatment” and “guidance of clinical pharmacists” are commonly used in medical institutions for the prevention of disputes, and “establishing a uniform and standard process”, “dealing with ADR in the first time” and “making relevant records” are common responses to disputes, while “waiving charges” has a low recognition degree.%目的 调查临床医师对药品不良反应(ADR)纠纷的防范和应对情况,探索医疗机构防范和应对ADR纠纷较为有效的方法.方法 对上海交通大学及其医学院的10家附属医院中的370名临床医师进行问卷调查,问卷分为两部分:第一部分为被调查者的基本情况;第二部分为专题调查,包括ADR基本概

  14. Investigation on the Infection of HIV, HCV and Association High Risk Factors among Drug Users%大理州吸毒人群HIV、HCV感染及相关高危因素调查研究

    Institute of Scientific and Technical Information of China (English)

    李泽; 刘继政; 申元英

    2016-01-01

    目的:了解大理州吸毒人群HIV、HCV感染情况及评估相关的高危因素,为更大范围内更有效地推广和完善吸毒哨点监测工作提供科学依据。方法:采集2015年1月至2015年6月大理州戒毒所新入所的423名吸毒人员的血样,检测HIV和HCV的感染情况,结合问卷调查资料,运用统计学方法分析与感染相关的危险因素。结果:在423名吸毒人员中HIV感染率为19.4%(82/423),HCV感染率为46.3%(196/423),在82例HIV感染者中,有96.3%(79/82)感染了HCV。多因素分析结果表明,注射吸毒年限、有注射吸毒史、共用针具不仅是HIV感染的高危因素,也是HCV感染的高危因素;此外,HCV感染还与年龄、每天注射吸毒次数正相关。结论:大理州吸毒人员中由于存在各种高危行为,使得吸毒人群HIV,HCV感染的比例较高,加速了HIV,HCV在该人群中的流行。%Objective:To understand the prevalence of HIV, HCV and estimate high risk factors among drug users in Dali Prefecture, thereby to provide the scientific basis for promoting and perfecting the prevention work more accurately in a larger range. Methods:The blood samples of 423 new drug users in Dali Detoxification Center from January 2015 to June 2015 were collected to detect the infection status of HIV and HCV. Using the data in questionnaire survey and statistical methods, risk factors related to infection were analyzed. Results: The infection rates among total 423 drug users were 19.4%(82/423)for HIV, 46.3%(196/423)for HCV. It is found that 96.3%(79/82)of the 82 HIV positive had infected with HCV. Multiple factor analysis indicated that the prevalence of HIV and HCV among drug users were positively related to drug using time, injection drug use, sharing needles. In addition, HCV infection was associated positively with the age of drug users and the times and quantity of drug addicts using per day. Conclusion:All sorts of high risk

  15. 我院2010-2012年抗生素药物不良反应报告调查和分析%Investigation and analysis on antibiotics adverse drug reaction reports in our hospital, 2010-2012

    Institute of Scientific and Technical Information of China (English)

    傅伟兰; 朱晓河; 丘利珠

    2013-01-01

    Objective To investigate and analyze the adverse reaction of antibiotic use cases in recent years,summarizing adverse reaction involving the heating organs and different kinds of antibiotics with adverse reaction in our hospital.Methods From 2010 to 2012,among patients using antibiotics,we selected 130 cases with adverse reactions,every year the number of cases showing adverse reactions was observed,using antibiotic occurrence trend and adverse reaction of antibiotics in the organs and tissues.Results The adverse reaction incidence of antibiotics was increasing year by year in our hospital,which had risen from 20.1% in 2010 to 40.1% in 2012; the main drugs causing adverse reaction was cephalosporin antibiotics,the main involving organs included the skin,nervous system and cardiovascular system,the skin involving adverse reaction was the most,occupying the proportion of 29.2%,with all statistical difference showing in all data,P < 0.05.Conclusion The principle of medication needs to be strictly followed during antibiotics use.Abuse of antibiotics should be prohibited,the combination therapy,which can reduce adverse reaction and improve the curative effect,should be advocated.%目的 调查分析近年来我院抗生素使用的不良反应病例,总结抗生素不良反应累及器官组织以及不良反应的抗生素种类.方法 回顾我院2010年至2012年抗生素使用患者,选取出现不良反应的患者130例,统计每年出现不良反应病例数目,观察抗生素使用不良反应的发生趋势以及抗生素不良反应累及的器官组织.结果 研究结果发现抗生素在我院使用产生的不良反应逐年呈上升趋势,由2010年20.1%增长到2012年40.1%;主要引起不良反应的药物为头孢菌素类抗生素,主要累及器官有皮肤、神经系统、心血管系统等,其中累及皮肤的副作用最多,比例达29.2%,差异有统计学意义(P<0.05).结论 抗生素使用需要严格遵循用药原则,禁

  16. Investigation of Resources and Varieties of Coptis Crude Drug Original Plant on Chinese Market%黄连药材原植物资源和市场品种调查

    Institute of Scientific and Technical Information of China (English)

    柳鑫; 黄河; 黄璐琦; 吴和珍; 杨艳芳

    2014-01-01

    目的::调查我国现有黄连资源状况和近年来黄连药材市售品种情况,为黄连的资源保护和品种整理研究提供依据。方法:在文献调查的基础上,采用实地调查、委托调查和访问调查等相结合的方法。结果:由于多年来环境的变迁,以及20世纪末对黄连资源的掠夺式开发,黄连野生资源的生态环境发生了较大的变化,野生资源破坏严重,资源蕴藏量急剧减少,尤其是野生雅连、云连,资源已濒临灭绝。全国市场上的主流商品为味连,云连次之,云连在其分布区(云南)的小规模医疗诊所以及药材市场中常见,未见雅连商品药材。结论:为了稳定黄连市场的供求关系,确保药农利益;进一步提高黄连的生产技术,确定栽培区域和适宜栽培品种,确保黄连药材质量,国家应重视黄连资源的变化情况,应进一步加大野生黄连资源的保护力度,确保黄连资源的可持续发展;政府相关部门应合理指导黄连的生产。%Objective::To understand the resources distribution and varieties of crude drug Coptis chinensis Franch. on Chinese market to provide scientific basis for the resource conservation and variety collection and studies of the Chinese medicine. Methods:On the basis of literature survey, field investigation, mandatory survey and interview survey were conducted. Results:Due to the chan-ges in environment for many years and the predatory development in Coptis resources at the end of 20th century, the ecological environ-ment of wild Coptis resources changed significantly with destructed resources and decreased reserves, especially wild Yalian and Yun-lian were on the verge of extinction. The mainstream product on Chinese market was Weilian followed by Yunlian mainly used in small-scale medical clinic and medicine market in the distribution area, while Yalian commodity medicine could not found. Conclusion::The supply and

  17. Drugs and sexual behavior.

    Science.gov (United States)

    Bruno, Antonio; Scimeca, Giuseppe; Marino, Antonio G; Mento, Carmela; Micò, Umberto; Romeo, Vincenzo M; Pandolfo, Gianluca; Zoccali, Rocco; Muscatello, Maria R A

    2012-01-01

    This study investigated the association between drugs and sexual behavior in a sample of polydrug substance abusers recruited from several Italian therapeutic communities; participants were 90 polydrug substance abusers (opiates, cocaine, amphetamine, inhalants, marijuana/sedatives or hallucinogens abusers) who were compared with 90 nonsubstance-abusing individuals. Sexual behavior was measured by the Italian version of the Sex and the Average Woman (or Man; SAWM), a questionnaire that assesses different kind of sexual attitudes. Results showed that drug-abusing individuals are particularly inclined to search for sexual intercourse and are open to different kinds of sexual experiences; however, they have difficulties in establishing committed and deep relationships with their partners, showing signs of inhibition, affective detachment or anger. Their sexual lives are also surrounded by negative emotions, disturbing thoughts and maladjusted behaviors. The importance of integrating sexual problems into therapeutic strategies is discussed.

  18. Personality, Drug Preference, Drug Use, and Drug Availability

    Science.gov (United States)

    Feldman, Marc; Boyer, Bret; Kumar, V. K.; Prout, Maurice

    2011-01-01

    This study examined the relationship between drug preference, drug use, drug availability, and personality among individuals (n = 100) in treatment for substance abuse in an effort to replicate the results of an earlier study (Feldman, Kumar, Angelini, Pekala, & Porter, 2007) designed to test prediction derived from Eysenck's (1957, 1967)…

  19. Personality, Drug Preference, Drug Use, and Drug Availability

    Science.gov (United States)

    Feldman, Marc; Boyer, Bret; Kumar, V. K.; Prout, Maurice

    2011-01-01

    This study examined the relationship between drug preference, drug use, drug availability, and personality among individuals (n = 100) in treatment for substance abuse in an effort to replicate the results of an earlier study (Feldman, Kumar, Angelini, Pekala, & Porter, 2007) designed to test prediction derived from Eysenck's (1957, 1967)…

  20. 103份肝胆疾病辅助用药说明书的调查分析%Investigation and Analysis of 103 Package Inserts of Auxiliary Liver Disease Drug

    Institute of Scientific and Technical Information of China (English)

    潘一敏; 郑绯; 赵庆国; 朱姗薇; 徐娟

    2014-01-01

    Objective To provide reference for the complete inserts of auxiliary liver disease drug,improve the level of rational drug use. MethodsAccording to the standard issued by State Food and Drug Administration,103 package inserts of auxiliary liver disease drug were analyzed on the basis of clinical practice. Results The survey of 103 instructions,the project marked rate of the chemical medicine was higher than traditional Chinese medicine,imported drugs was higher than the domestic medicine.Description of the drug of chemical medicine content details,much better than the quality of traditional Chinese medicine. Imported drugs more detailed instructions. Special Populations project instructions and interaction marked lower rate,marked less proprietary in Chinese medicines instructions on the pharmacology and toxicology. ConclusionThe part of the contents of the auxiliary liver disease medication instructions are incomplete,especially Chinese patent medicine manual,so that it can not play the role of guide rational drug.Recommendations to strengthen management,to supplement and improve the content of the manual,and provide strong support for the rational use of clinical.%目的:完善肝胆疾病辅助用药的说明书,为合理使用肝胆疾病辅助用药提供参考。方法结合临床实际需要对103份肝胆疾病辅助用药说明书进行调查分析,进行综合分析。结果调查的103份说明书中,化学药品的项目标注率高于中药的项目标注率,进口药品的项目标注率高于国产药品的项目标注率。化学药品说明书项目较全,内容较详,质量明显优于中药说明书。而进口药品说明书更加详细。说明书中特殊人群用药项目及相互作用的标注率较低,中成药说明书中关于药理毒理标注少。结论肝胆疾病辅助用药说明书部分内容还不够完整,尤其是中成药说明书,使其不能发挥指导临床合理用药的作用。建议加强管理,

  1. Intravenous drug delivery in neonates: lessons learnt.

    Science.gov (United States)

    Sherwin, Catherine M T; Medlicott, Natalie J; Reith, David M; Broadbent, Roland S

    2014-06-01

    Intravenous drug administration presents a series of challenges that relate to the pathophysiology of the neonate and intravenous infusion systems in neonates. These challenges arise from slow intravenous flow rates, small drug volume, dead space volume and limitations on the flush volume in neonates. While there is a reasonable understanding of newborn pharmacokinetics, an appreciation of the substantial delay and variability in the rate of drug delivery from the intravenous line is often lacking. This can lead to difficulties in accurately determining the pharmacokinetic and pharmacodynamic relationship of drugs in the smallest patients. The physical variables that affect the passage of drugs through neonatal lines need to be further explored in order to improve our understanding of their impact on the delivery of drugs by this route in neonates. Through careful investigation, the underlying causes of delayed drug delivery may be identified and administration protocols can then be modified to ensure predictable, appropriate drug input kinetics.

  2. Use of drugs for ADHD among adults

    DEFF Research Database (Denmark)

    Karlstad, Øystein; Zoëga, Helga; Furu, Kari

    2016-01-01

    PURPOSE: The use of ADHD drugs among adults is controversial and has until recently not been approved for use in adults in most countries. The aim was to investigate use of ADHD drugs (stimulants and atomoxetine) among the entire adult population in the Nordic countries. METHODS: We conducted...... a multinational population-based prescription register study based on the entire adult population in the five Nordic countries (Denmark, Finland, Iceland, Norway and Sweden). All users of ADHD drugs aged 18-64 years during 2008-2012 were included, which for 2012 comprised 76,896 drug users among 15.8 million...... period. Methylphenidate was used by 88 % of drug users. Treatment was discontinued within the first year by 21 % of new drug users. Among all users of ADHD drugs, 53 % of men and 64 % of women concurrently used other psychotropic drugs, most frequently antidepressants and hypnotics. Psychotropic co...

  3. 创新药物临床试验不良事件赔付机制调查研究%Investigation and analysis on the innovation drug adverse event relief system

    Institute of Scientific and Technical Information of China (English)

    孙磊; 林晶; 尹鹏; 李月明

    2015-01-01

    目前我国创新药物临床试验中针对出现的不良事件没有可以遵循的相关法律法规,尚未形成统一的赔付标准。本研究选取国家科技重大专项“创新药物临床评价技术平台”课题中标单位为调研对象,探讨建立创新药物临床不良事件赔付机制和实现赔付机制的途径、方式和方法。%Because lack of the law and unified compensation standards about compensation of innovation drug adverse event in China, the sufferers cannot get any compensation from the correlative responsibility party. By choosing the ‘Significant Innovation Drugs Creation’ bid units , this research carry out survey to find out and discuss the optimization approach to establish innovation drug adverse event compensation system.

  4. Practice of the First Time Online Bidding for Drug Purchase in a Large-scale Hospital in Anhui Province:Investigation and Analysis%安徽省某大型医院首次药品网上招标采购执行情况调查分析

    Institute of Scientific and Technical Information of China (English)

    徐维恒

    2009-01-01

    OBJECTIVE: To investigate the implementation and the outcome of the first time online bidding for drug purchase so as to provide reference of further standardizing the online bidding for drug purchase. METHODS: The data of the first time online bidding for drug purchase of a large grade three class A comprehensive hospital were subjected to a retro-spective statistical analysis with the use of Shanghai Jinshida Weining THIS4.0 system and Excel software. RESULTS: 86.06% of the drug varieties in this hospital underwent online bidding for drug purchase. The mean drug cost, per capita drug cost of outpatients and inpatients were reduced by 6.95% , 10.61% , and 1.10%, respectively. CONCLUSION: The online bidding for drug purchase contributes to the standardization of hospital drug purchase behavior and relieving of the problem of "high cost in medication" . However, which is far from perfect and thus remains to be improved further.%目的:考查安徽省首次药品网上招标采购的执行情况及其效果,为进一步规范药品网上招标采购提供参考.方法:采用上海金仕达卫宁THIS4.0系统和Excel软件,对某三级甲等大型综合性医院首次药品网上招标采购的执行数据进行回顾性统计分析.结果:医院执行品种比例达86.06%,药品零售价平均降幅6.95%,门诊和住院患者人均药品费用分别下降10.61%和1.10%.结论:药品网上招标采购对规范医院药品购销行为、解决百姓"看病贵"问题有积极作用,但与预期效果还有较大差距.需进一步完善.

  5. Investigation on Methadone Maintenance Treatment of 196 Drug Addicts in Yancheng City%盐城市196例吸毒者美沙酮维持治疗情况的调查

    Institute of Scientific and Technical Information of China (English)

    朱凤刚; 李志勇; 纪康; 方娟; 高鸣; 袁中行

    2011-01-01

    目的 了解进入美沙酮维持治疗门诊吸毒人群的人口学、吸毒行为、性行为等特征,为今后开展综合干预提供依据.方法 采用修改后的调查表对门诊接受治疗的196例吸毒者进行抽样调查.结果 男性84.18%,女性15.82%;HIV无阳性;HCV阳性率56.90%;梅毒ELISA和RPR均阳性的6.12%;最近一次尿吗啡检测阳性率24.49%;入组前以静脉注射吸毒为主的占80.61%,共用注射器的占12.03%;最近一次性行为安全套使用率为55.09%.结论 接受治疗的吸毒人员存在感染HIV和HCV高危行为,建议加强预防艾滋病、丙型肝炎和梅毒等健康教育和行为干预活动.%[Objective] To understand the demography, drug addicts behavior, sexual behavior of drug addicts who received metha-done maintenance treatment in clinic, and provide evidence for carrying out comprehensive intervention in the future. [Methods]The modified questionnaire was used to survey 196 drug addicts who received methadone maintenance treatment in clinic. [Results] 84. 18% were male and female of 15. 82% , The positive rate of HIV antibody test, HCV antibody test, Syphilis ELBA and RPR test, the most recent detection of urinary morphine test were 0, 56. 90% , 6. 12% , 6. 12% and 24. 49% respectively. Before treatment , the ratio of intravenous drug addicts, needle-sharing and condom utilization in last sexual behavior were 72. 96% , 9. 69% and 55. 09% respectively. [Conclusion] Drug addicts, who received treatment have high-risk behaviors of HIV and HCV infection. It is proposed to strengthen health education and behavioral interventions in the prevention of HIV/AIDS, HCV, syphilis, etc.

  6. 抗癫疒间肽纳米粒的制备及体外释药性能的研究%Preparation of anti-epilepsy peptide nanoparticles and investigation of the drug re-leasing characteristic in vitro

    Institute of Scientific and Technical Information of China (English)

    王石健; 王彬辉; 章文红; 张晓芬; 吴敏

    2014-01-01

    Objective To prepare anti-epilepsy peptide nanoparticles and evaluate its release characteristics in vitr. Methods Anti-epilepsy peptide nanoparticles were prepared by emulsion/solvent evaporation method and poly (ethylene glycol)-poly(lactide acid)-poly(glycolic acid)copolymer was used as carrier material. Encapsulation effi-ciency and drug loading were used to optimize the technique and evaluate its release characteristics in vitro. Results The appearance of all anti-epilepsy peptide nanoparticles were round or similar. The mean particle size,encapsulation efficiency and drug loading of anti-epilepsy peptide nanoparticles were ( 100. 2 ± 2. 45 ) nm, ( 64. 46 ± 1. 34 )% and (4. 73 ± 0. 32)%respectively. The drug release from nanoparticles appeared consisting of two phases with initial burst release and sustained-release in vitro,and the release rule accorded with Weibull equation. Conclusion The preparation technics is simple and feasible,and the obtained anti-epilepsy peptide nanoparticles has high encapsulation efficiency, high drug loading,small mean diameter and the drug releasing characteristic is sustained in vitro.%目的:制备抗癫疒间肽纳米粒,并研究其体外释药性能。方法选用聚乙二醇-聚乳酸-聚乙醇酸嵌段共聚物为载体,采用复乳-溶剂挥发法制备抗癫疒间肽纳米粒,以包封率、载药量等指标优化制备工艺,并研究纳米粒体外释药性能。结果抗癫疒间肽纳米粒外观呈圆形或类圆形,平均粒径为(100.2±2.45)nm,包封率和载药量分别为(64.46±1.34)%和(4.73±0.32)%,体外释药呈现缓释和突释两个阶段,符合Weibull方程。结论建立的制备工艺简便可行,得到的抗癫疒间肽纳米粒包封率和载药量较高,粒径小,体外释药具有明显的缓释特征。

  7. 广州市1324名吸毒人员HIV、 HBV、 HCV及梅毒感染状况调查%Investigation on infection status of HIV, HBV, HCV and syphilis among 1324 drug addicts in Guangzhou City

    Institute of Scientific and Technical Information of China (English)

    钟秋林; 刘展翅

    2012-01-01

    [Objective] To understand the infection status of HIV, HBV, HCV and syphilis among drug addicts in Guangzhou City provide the basis for developing the prevention and control measures of common infectious diseases among drug addicts in Guanj zhou. [ Methods] From July 2009 to June 2011, the venous blood samples were collected from 1 324 drug addicts in a detoxificatk center of Guangzhou city, and the anti-HIV , anti-HCV, HBsAg and syphilis antibody were tested. [ Results] Among 1 324 dnifc addicts, 74 cases were positive for anti-HIV with the positive rate of 4,2% f the positive rate of HBsAg was 12.2% , that of anti-HCV was 40.5% , and that of treponema pallidum particle agglutination assay (TPPA) was 6. 1%. 21.8% of drug addicts were dectected with two infectious diseases, and 2,2% were detected with three infectious diseases. [ Conclusion]The infection rates of HIV, HBV, HCV and syphilis among drug addicts in Guangzhou city are high, and it is important to pay attention to supervision, monitoring and education in this population.%目的 了解广州市吸毒人群HIV 、HBV 、HCV及梅毒感染状况,为制定针对该地区吸毒人群常见传染病的防治措施提供依据.方法 于2009年7月-2011年6月,抽取广州市某戒毒所收入的1324例吸毒人员静脉血,检测HIV 、HCV和梅毒抗体以及HBV表面抗原.结果 1324例吸毒人群中,HIV抗体阳性74例,阳性率4.2%;乙肝表面抗原阳性率12.2%,丙肝抗体阳性率40.5%,梅毒螺旋体明胶颗粒凝集试验(TPPA)阳性率6.1%. 21.8%的吸毒人员同时检出2种传染病,2.2%的吸毒者同时检出3种传染病.结论 广州市吸毒人群中HCV、HBV、梅毒及HIV仍存在较高的感染率,应继续重视对该人群的监管监测及宣传教育.

  8. Food and Drug Administration Drug Approval Process: A History and Overview.

    Science.gov (United States)

    Williams, Christopher Ty

    2016-03-01

    In this article, the processing of investigational and new drug applications is described and the standard and expedited review processes are examined. The efforts of the US Food and Drug Administration to ensure greater agency transparency and fiscal responsibility and intensify oversight during the drug development and approval process are reviewed. Often attributed to a decrease in the number of uninsured adults, both the increase in prescription drug sales and the high costs associated with bringing a new drug to market highlight the necessity for a streamlined and cost-effective process to deliver these drugs safely and effectively.

  9. Behavioral economics of drug self-administration and drug abuse policy.

    Science.gov (United States)

    Hursh, S R

    1991-09-01

    The concepts of behavioral economics have proven useful for understanding the environmental control of overall levels of responding for a variety of commodities, including reinforcement by drug self-administration. These general concepts are summarized for application to the analysis of drug-reinforced behavior and proposed as the basis for future applications. This behavioral agenda includes the assessment of abuse liability, the assay of drug-reinforcer interactions, the design of drug abuse interventions, and the formulation of drug abuse public policy. These separate domains of investigation are described as part of an overall strategy for designing model projects to control drug use and testing public policy initiatives.

  10. Microemulsion Drug Delivery Systems for Radiopharmacy Studies

    Directory of Open Access Journals (Sweden)

    Emre Ozgenc

    2016-11-01

    Full Text Available Microemulsions have been used increasingly for last year’s because of ideal properties like favorable drug delivery, ease of preparation and physical stability. They have been improved the solubility and efficacy of the drug and reduce the side effects. Use of radiolabeled microemulsions plays an alternative role in drug delivery systems by investigating the formation, stability and application of microemulsions in radiopharmacy. Gama scintigraphic method is well recognized for developing and detecting the biodistribution of newly developed drugs or formulation. This review will focus on how radionuclides are able to play role with characterization studies of microemulsion drug delivery systems.

  11. AIDSinfo Drug Database

    Science.gov (United States)

    ... U V W X Y Z All Drugs Drug News Thursday, February 2, 2017 Sustiva Drug Label Updated ... Drug Label Updated Tuesday, January 31, 2017 Stribild Drug Label Updated More News Mobile Apps iPhone/iPad App Android App Back ...

  12. Drug Treatment

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008358 The effect of activating retinoid X receptor inhibiting hydrogen peroxide-induced apoptosis in cultured rat neonatal cardiomyocytes. SHAN Peiren(单培仁), et al. Cardiovasc Dept, Renji Hosp, Shanghai Jiaotong Univ Med Coll, Shanghai 200127. Chin J Emerg Med 2008;17(5):464-468. Objective To investigate the effect of 9-cis retinoid acid (c-RA), a retinoid X receptor (RXR)agonist, on hydrogen peroxide (H2O2) induced

  13. Managing Drug Use in Danish Club Settings: A normalized enterprise?

    DEFF Research Database (Denmark)

    Ravn, Signe

    2012-01-01

    The article analyzes Danish clubbers’ strategies for taking drugs in night clubs. This exploration is framed within the discussion of a possible normalization of youth drug use. Thus, the article investigates how young drug-users experience the level of acceptability of drug use in clubs and how...

  14. Characteristics and drug utilization patterns for heavy users of prescription drugs among the elderly

    DEFF Research Database (Denmark)

    Øymoen, Anita; Pottegård, Anton; Almarsdóttir, Anna Birna

    2015-01-01

    PURPOSE: The objectives of this study were to (1) identify and characterize heavy users of prescription drugs among persons aged 60 years and above; (2) investigate the association of demographic, socioeconomic, and health-related variables with being a heavy drug user; and (3) study the most...... frequently used drugs among heavy drug users and development in use over time. METHOD: This is a descriptive study. Heavy drug users were defined as the accumulated top 1 percentile who accounted for the largest share of prescription drug use measured in number of dispensed defined daily doses (DDDs......). The nationwide Danish registers were used to obtain data. Multivariable logistic binary regression was used to determine which factors were associated with being a heavy drug user. RESULTS: Heavy drug users among persons aged 60 years and above accounted for 6.8, 6.0, and 5.5% of prescription drug use in 2002...

  15. The empirical war on drugs.

    Science.gov (United States)

    Vitellone, Nicole

    2013-05-01

    In a special issue of the journal Addictions (1995) academics, researchers and health care professionals debated the status of the empirical in socially orientated drugs research. A number of researchers noted that our knowledge and understanding of drugs and drug users has changed significantly since the 1990s. Post AIDS this shift is identified as a consequence of the development of qualitative research methods. The qualitative turn in drugs research has involved a shift away form traditional epidemiological approaches and the pursuit of more socially focused methods. Whilst qualitative research has yielded important empirical data on risk behavior the pursuit of these methods has not been without controversy. In addressing the debate on methods in the drugs field this article investigates the effects of social science methods for research on injecting drug use. In so doing I examine what counts and what gets left out of research on injecting beaviour. Drawing on Actor Network Theory (ANT) I suggest Bruno Latour's methodological approach offers critical insights for addressing the empirical objects of injecting drug use. Copyright © 2013 Elsevier B.V. All rights reserved.

  16. 不同药物对兔耳缘静脉炎症及血栓形成的影响%Investigation on inflammation reaction and vein thrombosis on rabbit ear vein with different drugs

    Institute of Scientific and Technical Information of China (English)

    戴晴; 李伦兰; 陈学岚

    2016-01-01

    To observe local inflammation reaction and vein thrombosis on rabbit ear vein with methotrexate , ceftri-axone sodium and normal saline .With the extension use of drugs , the numbers of inflammation reaction and throm-bosis in each group were increased , and antibiotic and chemotherapy drug group had a higher rate than the normal saline group .There was a statistically significant difference of the inflammation reaction between the three test groups on the 3rd and 7th day (P<0.05), and a statistically significant difference of thrombosis between the three test groups on the 7 th day ( P<0.05 ) .The physical-chemical properties of drugs and use of time were factors in-fluencing inflammation reaction and thrombosis .%观察甲氨蝶呤、头孢曲松钠和生理盐水3种不同药物对兔耳缘静脉炎症反应及血栓形成的影响。随着药物使用时间的增加,3组静脉炎症反应和血栓形成数量均逐渐增加,化疗药组和抗生素组明显多于生理盐水组。3组在药物使用第3、7天时静脉炎症反应差异有统计学意义(P <0.05),在药物使用第7天血栓形成差异有统计学意义(P<0.05)。药物的理化性质及使用时间对静脉炎症反应及血栓的形成的影响有所差异。

  17. Writing Points of Review Data for Clinical Pharmaceutical Research of In-vestigational New Drug Application in TCM%中药新药申请临床药学研究综述资料的撰写要点

    Institute of Scientific and Technical Information of China (English)

    马秀瞡; 张永文; 阳长明

    2014-01-01

    Pharmaceutical research is the important component of the research and development of new drug in TCM and is the foundation of drug safety and effectiveness study as well as evaluation.The re-view data of pharmaceutical research is the summary,analysis and evaluation of the study work,which is sig-nificant for the applicants and reviewers to completely understand the situation of pharmaceutical research. With the constant improvements on the recognition of new drug study,in association of the review experi-ences,the writing points were introduced on the review data for the application of pharmaceutical research on clinical trial registration stage so as to provide the reference for the researchers and reviewers and improve the quality and efficiency of registration application.%药学研究是中药新药研发的重要组成部分,是进行药物安全性、有效性研究和评价的基础。药学研究综述资料是对药学研究工作的总结、分析与评价,对于申请人和审评者全面了解药学研究情况具有重要的意义。随着对新药研究认识的不断提高,结合审评体会,本文对申请临床试验注册阶段药学研究综述资料的撰写要点提出建议,供研究和评价者参考,以提高注册申请的质量和效率。

  18. 耐甲氧西林金黄色葡萄球菌的临床调查与耐药性分析%Clinical investigation of methicillin-resistant Staphylococcus aureus and drug resistance

    Institute of Scientific and Technical Information of China (English)

    崔金国; 孙景生; 邹万芹

    2012-01-01

    OBJECTIVE To explore the characteristics of clinical infections caused by methicillin-resistant Staphylococcus aureus (MRSA). and drug resistance. METHODS From Jan 2009 to Jun 2011, the distribution of the specimens and the departments from which 103 strains of MRSA as well as the drug resistance was analyzed. RESULTS MRSA infection mainly distributed in neurosurgery department (35. 9%) and ICU(20. 4%) ; totally the 103 strains of MRSA were mainly isolated from the sputum and the wound secretion, accounting for 43. 7% and 22.3%; MRSA varied in drug resistance to macrolides, aminoglycosides, quinolones, and sulfonamides except vancomycin. CONCLUSION Only we grasp the distribution and the characteristics of MRSA infections, monitor its drug resistance and reasonably use antibiotics can we effectively control the MRSA infections and its spread.%目的 探讨耐甲氧西林金黄色葡萄球菌(MRSA)临床感染的特点及对抗菌药物的耐药性.方法 对2009年1月-2011年6月医院临床送检各类标本中分离出的103株MRSA,按照标本种类、科室分布、药物耐药性等进行分析.结果 医院感染MRSA较多科室为神经外科及ICU,分别占35.9%、20.4%;103株MRSA主要标本来源为痰液、伤口分泌物,分别占43.7%、22.3%;MRSA除对万古霉素敏感外,对大环内酯类、氨基糖苷类、喹诺酮类及磺胺类药物呈不同耐药性,对青霉素和苯唑西林的耐药性为100.0%.结论 只有正确掌握MRSA感染的分布与特征、监测其耐药性,合理使用抗菌药物,才能有效控制MRSA感染及扩散.

  19. Quantitative investigation of the brain-to-cerebrospinal fluid unbound drug concentration ratio under steady-state conditions in rats using a pharmacokinetic model and scaling factors for active efflux transporters.

    Science.gov (United States)

    Kodaira, Hiroshi; Kusuhara, Hiroyuki; Fuse, Eiichi; Ushiki, Junko; Sugiyama, Yuichi

    2014-06-01

    A pharmacokinetic model was constructed to explain the difference in brain- and cerebrospinal fluid (CSF)-to-plasma and brain-to-CSF unbound drug concentration ratios (Kp,uu,brain, Kp,uu,CSF, and Kp,uu,CSF/brain, respectively) of drugs under steady-state conditions in rats. The passive permeability across the blood-brain barrier (BBB), PS1, was predicted by two methods using log(D/molecular weight(0.5)) for PS1(1) or the partition coefficient in octanol/water at