WorldWideScience

Sample records for veterinary drug bioequivalence

  1. Bioequivalence and other unresolved issues in generic drug substitution.

    Science.gov (United States)

    Meredith, Peter

    2003-11-01

    Substitution of generic drugs for brand-name products is highly controversial and often is met with suspicion by health care providers and patients. Historically, the debate has focused on the issue of bioequivalence, and clinical practice has identified a number of drug classes for which generic substitution should be approached with caution. Current bioequivalence requirements are based on a measure of average bioequivalence; however, there are fears that use of this measure may be inappropriate in the case of a drug with a narrow or wide therapeutic range or high intrasubject or intersubject variability. Under these circumstances, measures of individual and population bioequivalence are proposed to be more accurate than measures of average bioequivalence. This paper addresses issues of bioequivalence and other concerns with generic drug substitution. I conducted a MEDLINE search of the English-language literature containing the key terms generic, multisource, quality, and brand and published between 1973 and 2003. The names of branded pharmaceuticals whose patents had recently expired (eg, Ventolin HFA, Adalat, Capoten, Tagamet HB 200, and Valium) also were used to search for articles on generic substitution. Reference lists of relevant articles also were searched. Bioequivalence issues are presented together with more general concerns over generic drug substitution, such as consumer perception of risk, differences in product and packaging appearance, and differences in excipients. The literature reviewed act to highlight a number of different drug categories and patient subpopulations for which generic substitution can still prove to be problematic. I recommend that health care providers continue to exercise caution in the consideration of generic drug substitution under certain circumstances.

  2. Novel bioequivalence approach for narrow therapeutic index drugs.

    Science.gov (United States)

    Yu, L X; Jiang, W; Zhang, X; Lionberger, R; Makhlouf, F; Schuirmann, D J; Muldowney, L; Chen, M-L; Davit, B; Conner, D; Woodcock, J

    2015-03-01

    Narrow therapeutic index drugs are defined as those drugs where small differences in dose or blood concentration may lead to serious therapeutic failures and/or adverse drug reactions that are life-threatening or result in persistent or significant disability or incapacity. The US Food and Drug Administration proposes that the bioequivalence of narrow therapeutic index drugs be determined using a scaling approach with a four-way, fully replicated, crossover design study in healthy subjects that permits the simultaneous equivalence comparison of the mean and within-subject variability of the test and reference products. The proposed bioequivalence limits for narrow therapeutic index drugs of 90.00%-111.11% would be scaled based on the within-subject variability of the reference product. The proposed study design and data analysis should provide greater assurance of therapeutic equivalence of narrow therapeutic index drug products. © 2014 American Society for Clinical Pharmacology and Therapeutics.

  3. Rethinking bioequivalence and equivalence requirements of orally inhaled drug products

    Directory of Open Access Journals (Sweden)

    Dina Al-Numani

    2015-12-01

    Full Text Available Orally inhaled drug products (OIPs, such as corticosteroids and bronchodilators, are at the forefront of asthma and chronic obstructive pulmonary disease treatments, two diseases that afflict worldwide populations. Introducing generics of these products is essential, as the pricing of these medications remain a barrier to adequate patient care. Currently, there is no consensus between regulatory bodies as to the bioequivalence and equivalence requirements of OIPs that are intended for local action in the lungs. This manuscript critically reviews these requirements and presents future directions for clinicians, scientists, and regulators to consider to optimize the development and approval of OIPs.

  4. 21 CFR 201.105 - Veterinary drugs.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Veterinary drugs. 201.105 Section 201.105 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL LABELING Exemptions From Adequate Directions for Use § 201.105 Veterinary drugs. A drug subject to the...

  5. From antiretroviral originator to generic drugs: bioequivalence and pharmacovigilance.

    Science.gov (United States)

    Bagheri, H; Garraffo, R; Dellamonica, P

    2014-10-01

    Antiretroviral drugs have been available in generic form in developing countries, which has expanded access to treatment; they have also become available in developed countries more recently. The validation of generic drugs (GD) compared to originator drugs (OD) is mandatory to ensure that using generics will lead to a decreased cost of treatment. The results were obtained by analyzing published data as well as European Medicines Agency recommendations. The GD should have the same qualitative and quantitative active principle formula, the same pharmaceutical forms, and the same criteria in terms of quality, effectiveness, and safety. This equivalence is based on bioequivalence rules: comparison of the concentration/time curves (AUC); Cmax and Tmax (90%), for which the confidence intervals in the range of 80-125% should be included. Naturally, that does not mean that the concentrations can vary from 80 to 125%: this would indicate unacceptable deviations. Conforming to these criteria allows substituting an OD by a GD. Adverse effects should not be different from those observed for the OD. Adverse effects observed when the GD is used must be notified, as is the case for the OD. Accountability is established according to 4 essential pieces of information: a prescriber, a patient, a drug, and an adverse effect. It is sometimes difficult to identify the provider of the GD that has been delivered. The level of safety concerning effectiveness and tolerance required is identical for OD and GD, in Europe. Analyzing confirmed adverse effects and therapeutic failures is the only way to identify differences that could question a GD's effectiveness. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  6. Demonstrating comparative in vitro bioequivalence for animal drug products through chemistry and manufacturing controls and physicochemical characterization: a proposal.

    Science.gov (United States)

    Martinez, Marilyn N; Fahmy, Raafat

    2015-03-01

    The assessment of in vivo bioequivalence (BE) of nonsystemically absorbed drug products has been a longstanding challenge facing drug manufacturers and regulators of human or animal health products. Typically, in situations where blood level BE studies are not feasible, clinical endpoint BE trials have provided the only option for generating interproduct comparisons. Given the imprecision and logistic challenges associated with these studies, there has been an effort to identify alternative pathways that can reliably ensure the equivalence of product performance and quality. This commentary provides a proposal for an in vitro approach for evaluating the in vivo BE of veterinary drug products that are either nonsystemically absorbed or that act both locally and systemically but where the local site of action is proximal to the absorption window. The assumption underlying this approach is that equivalence in product physicochemical attributes and in vitro product performance translates to equivalence in product in vivo behavior. For sponsors with a right of reference to underlying safety and effectiveness data, this approach could be used to support pre and post-approval changes. When comparing a generic test product to the pioneer (reference listed new animal drug, RLNAD) product, a demonstration of sameness across a battery of in vitro test procedures could be used to confirm that the test and RLNAD products are bioequivalent.

  7. Comparison of veterinary drugs and veterinary homeopathy: part 1.

    Science.gov (United States)

    Lees, P; Pelligand, L; Whiting, M; Chambers, D; Toutain, P-L; Whitehead, M L

    2017-08-12

    For many years after its invention around 1796, homeopathy was widely used in people and later in animals. Over the intervening period (1796-2016) pharmacology emerged as a science from Materia Medica (medicinal materials) to become the mainstay of veterinary therapeutics. There remains today a much smaller, but significant, use of homeopathy by veterinary surgeons. Homeopathic products are sometimes administered when conventional drug therapies have not succeeded, but are also used as alternatives to scientifically based therapies and licensed products. The principles underlying the veterinary use of drug-based and homeopathic products are polar opposites; this provides the basis for comparison between them. This two-part review compares and contrasts the two treatment forms in respect of history, constituents, methods of preparation, known or postulated mechanisms underlying responses, the legal basis for use and scientific credibility in the 21st century. Part 1 begins with a consideration of why therapeutic products actually work or appear to do so. British Veterinary Association.

  8. 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.

  9. Quality of Reporting of Bioequivalence Trials Comparing Generic to Brand Name Drugs: A Methodological Systematic Review

    Science.gov (United States)

    van der Meersch, Amélie; Dechartres, Agnès; Ravaud, Philippe

    2011-01-01

    Background Generic drugs are used by millions of patients for economic reasons, so their evaluation must be highly transparent. Objective To assess the quality of reporting of bioequivalence trials comparing generic to brand-name drugs. Methodology/Principal Findings PubMed was searched for reports of bioequivalence trials comparing generic to brand-name drugs between January 2005 and December 2008. Articles were included if the aim of the study was to assess the bioequivalency of generic and brand-name drugs. We excluded case studies, pharmaco-economic evaluations, and validation dosage assays of drugs. We evaluated whether important information about funding, methodology, location of trials, and participants were reported. We also assessed whether the criteria required by the Food and Drug Administration (FDA) and the European Medicine Agency (EMA) to conclude bioequivalence were reported and that the conclusions were in agreement with the results. We identified 134 potentially relevant articles but eliminated 55 because the brand-name or generic drug status of the reference drug was unknown. Thus, we evaluated 79 articles. The funding source and location of the trial were reported in 41% and 56% of articles, respectively. The type of statistical analysis was reported in 94% of articles, but the methods to generate the randomization sequence and to conceal allocation were reported in only 15% and 5%, respectively. In total, 65 articles of single-dose trials (89%) concluded bioequivalence. Of these, 20 (31%) did not report the 3 criteria within the limits required by the FDA and 11 (17%) did not report the 2 criteria within the limits required by the EMA. Conclusions/Significance Important information to judge the validity and relevance of results are frequently missing in published reports of trials assessing generic drugs. The quality of reporting of such trials is in need of improvement. PMID:21858184

  10. Bioequivalence studies: need for the reability of generic drugs

    OpenAIRE

    Laosa, Olga; Centro de Farmacología Clínica, Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma de Madrid. Madrid, España. Médico especialista en Farmacología Clínica.; Guerra, Pedro; Centro de Farmacología Clínica, Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma de Madrid. Madrid, España. Médico especialista en Farmacología Clínica.; López-Durán, Jose Luis; Centro de Farmacología Clínica, Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma de Madrid. Madrid, España. Médico especialista en Farmacología Clínica.; Mosquera, Beatriz; Centro de Farmacología Clínica, Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma de Madrid. Madrid, España. Licenciada en Ciencias Químicas.; Frías, Jesús; Centro de Farmacología Clínica, Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma de Madrid. Madrid, España. Servicio de Farmacología Clínica, Hospital Universitario la Paz. Madrid, España. Médico especialista en Farmacología Clínica.

    2009-01-01

    A generic medicine is a pharmaceutical product containing an active ingredient already known and previously developed and invented by others. The cost of these generic or multisource products should be less than their counterparts original. The clinical effects and the risk-benefit balance of a medicine do not depend exclusively on the activity of a pharmacologically active substance. Demonstration of bioequivalence of generic medicine is of great importance. In Europe and the United States g...

  11. Distribution of veterinary drug residues among muscles

    Science.gov (United States)

    The U.S. Food and Drug Administration sets tolerances for veterinary drug residues in muscle, but does not specify which muscle should be sampled for analysis. The goal of this research was to determine if antibiotic residue levels are dependent on muscle type. In this study, penicillin G (Pen G) d...

  12. Bioequivalence study designs for generic solid oral anticancer drug products: scientific and regulatory considerations.

    Science.gov (United States)

    Kaur, Paramjeet; Chaurasia, Chandra S; Davit, Barbara M; Conner, Dale P

    2013-12-01

    The demonstration of bioequivalence (BE) between the test and reference products is an integral part of generic drug approval process. A sound BE study design is pivotal to the successful demonstration of BE of generic drugs to their corresponding reference listed drug product. Generally, BE of systemically acting oral dosage forms is demonstrated in a crossover, single-dose in vivo study in healthy subjects. The determination of BE of solid oral anticancer drug products is associated with its own unique challenges due to the serious safety risks involved. Unlike typical BE study in healthy subjects, the safety issues often necessitate conducting BE studies in cancer patients. Such BE studies of an anticancer drug should be conducted without disturbing the patients' therapeutic dosing regimen. Attributes such as drug permeability and solubility, pharmacokinetics, dosing regimen, and approved therapeutic indication(s) are considered in the BE study design of solid anticancer drug products. To streamline the drug approval process, the Division of Bioequivalence posts the Bioequivalence Recommendations for Specific Products guidances on the FDA public website. The objective of this article is to illustrate the scientific and regulatory considerations in the design of BE studies for generic solid oral anticancer drug products through examples. © 2013, The American College of Clinical Pharmacology.

  13. International guidelines for bioequivalence of systemically available orally administered generic drug products: a survey of similarities and differences.

    Science.gov (United States)

    Davit, Barbara; Braddy, April C; Conner, Dale P; Yu, Lawrence X

    2013-10-01

    The objective of this article is to discuss the similarities and differences among bioequivalence approaches used by international regulatory authorities when reviewing applications for marketing new generic drug products which are systemically active and intended for oral administration. We focused on the 13 jurisdictions and organizations participating in the International Generic Drug Regulators Pilot. These are Australia, Brazil, Canada, China, Chinese Taipei, the European Medicines Association, Japan, Mexico, Singapore, South Korea, Switzerland, the USA, and the World Health Organization. We began with a comparison of how the various jurisdictions and organizations define a generic product and its corresponding reference product. We then compared the following bioequivalence approaches: recommended bioequivalence study designs, method of pharmacokinetic calculations and bioequivalence acceptance limits, recommendations for modifying bioequivalence study designs and limits for highly variable drugs and narrow therapeutic index drugs, provisions for waiving bioequivalence study requirements (granting biowaivers), and implementation of the Biopharmaceutics Classification System. We observed that, overall, there are more similarities than differences in bioequivalence approaches among the regulatory authorities surveyed.

  14. Bioavailability and Bioequivalence Aspects of Oral Modified-Release Drug Products.

    Science.gov (United States)

    Wang, Rong; Conner, Dale P; Li, Bing V

    2017-03-01

    Oral modified-release (MR) products are dosage forms administered through the mouth and designed to release drug in a controlled manner to achieve maximum efficacy, minimal side effects, and better patient compliance. With significant progress in pharmaceutical technologies and favored therapeutic benefit, more and more oral MR products including the generic versions of these products are being developed, marketed, and used in the USA. Because different types of MR products may exhibit unique drug release modes and specific pharmacokinetic profiles, a better understanding of the regulation and evaluation of these generic MR products can help development and marketing of generic MR products that are therapeutically equivalent to the corresponding reference product. This review summarizes the general regulatory requirements for establishing bioequivalence between generic and reference oral MR products. In addition, some special regulatory considerations for bioequivalence evaluation are highlighted with examples of specific oral MR drug products.

  15. Comparing generic and innovator drugs: a review of 12 years of bioequivalence data from the United States Food and Drug Administration.

    Science.gov (United States)

    Davit, Barbara M; Nwakama, Patrick E; Buehler, Gary J; Conner, Dale P; Haidar, Sam H; Patel, Devvrat T; Yang, Yongsheng; Yu, Lawrence X; Woodcock, Janet

    2009-10-01

    In the US, manufacturers seeking approval to market a generic drug product must submit data demonstrating that the generic formulation provides the same rate and extent of absorption as (ie, is bioequivalent to) the innovator drug product. Thus, most orally administered generic drug products in the US are approved based on results of one or more clinical bioequivalence studies. To evaluate how well the bioequivalence measures of generic drugs approved in the US over a 12-year period compare with those of their corresponding innovator counterparts. This retrospective analysis compared the generic and innovator bioequivalence measures from 2070 single-dose clinical bioequivalence studies of orally administered generic drug products approved by the Food and Drug Administration (FDA) from 1996 to 2007 (12 y). Bioequivalence measures evaluated were drug peak plasma concentration (C(max)) and area under the plasma drug concentration versus time curve (AUC), representing drug rate and extent of absorption, respectively. The generic/innovator C(max) and AUC geometric mean ratios (GMRs) were determined from each of the bioequivalence studies, which used from 12 to 170 subjects. The GMRs from the 2070 studies were averaged. In addition, the distribution of differences between generic means and innovator means was determined for both C(max) and AUC. The mean +/- SD of the GMRs from the 2070 studies was 1.00 +/- 0.06 for C(max) and 1.00 +/- 0.04 for AUC. The average difference in C(max) and AUC between generic and innovator products was 4.35% and 3.56%, respectively. In addition, in nearly 98% of the bioequivalence studies conducted during this period, the generic product AUC differed from that of the innovator product by less than 10%. The criteria used to evaluate generic drug bioequivalence studies support the FDA's objective of approving generic drug formulations that are therapeutically equivalent to their innovator counterparts.

  16. Bioequivalence Evaluations of Generic Dry Powder Inhaler Drug Products: Similarities and Differences Between Japan, USA, and the European Union.

    Science.gov (United States)

    Kuribayashi, Ryosuke; Yamaguchi, Toru; Sako, Hanaka; Takishita, Tomoko; Takagi, Kazunori

    2017-03-01

    In Japan, the development of generic oral dry powder inhaler (DPI) drug products for marketing approval has recently increased. The Pharmaceuticals and Medical Devices Agency (PMDA) considers the required data for each drug product in the consultation meeting. However, guidelines for DPI drug products have been published by the US Food and Drug Administration and the European Medicines Agency. Recently, the basic principles of bioequivalence evaluations of generic DPI drug products were published in March 2016 by the Ministry of Health, Labour and Welfare. The document mainly outlines the current understanding regarding the bioequivalence evaluations of generic DPI drug products based on knowledge from PMDA consultation meetings. In this review, we compared the bioequivalence evaluations of DPI drug products among Japan, USA, and the European Union and discuss future development of generic DPI drug products in Japan.

  17. Regulatory framework on bioequivalence criteria for locally acting gastrointestinal drugs: the case for oral modified release mesalamine formulations.

    Science.gov (United States)

    Sferrazza, Gianluca; Siviero, Paolo D; Nicotera, Giuseppe; Turella, Paola; Serafino, Annalucia; Blandizzi, Corrado; Pierimarchi, Pasquale

    2017-09-01

    Bioequivalence testing for locally acting gastrointestinal drugs is a challenging issue for both regulatory authorities and pharmaceutical industries. The international regulatory framework has been characterized by the lack of specific bioequivalence tests that has generated a negative impact on the market competition and drug use in clinical practice. Areas covered: This review article provides an overview of the European Union and United States regulatory frameworks on bioequivalence criteria for locally acting gastrointestinal drugs, also discussing the most prominent scientific issues and advances that has been made in this field. A focus on oral modified release mesalamine formulations will be also provided, with practical examples of the regulatory pathways followed by pharmaceutical companies to determine bioequivalence. Expert commentary: The development of a scientific rationale to demonstrate bioequivalence in this field has been complex and often associated with uncertainties related to scientific and regulatory aspects. Only in recent years, thanks to advanced knowledge in this field, the criteria for bioequivalence assessment are undergoing substantial changes. This new scenario will likely result in a significant impact on pharmaceutical companies, promoting more competition through a clearer regulatory approach, conceived for streamlining the demonstration of therapeutic equivalence for locally acting gastrointestinal drugs.

  18. Antimicrobial drug use in veterinary medicine.

    Science.gov (United States)

    Morley, Paul S; Apley, Michael D; Besser, Thomas E; Burney, Derek P; Fedorka-Cray, Paula J; Papich, Mark G; Traub-Dargatz, Josie L; Weese, J Scott

    2005-01-01

    Recognizing the importance of antimicrobial resistance and the need for veterinarians to aid in efforts for maintaining the usefulness of antimicrobial drugs in animals and humans, the Board of Regents of the American College of Veterinary Internal Medicine charged a special committee with responsibility for drafting this position statement regarding antimicrobial drug use in veterinary medicine. The Committee believes that veterinarians are obligated to balance the well-being of animals under their care with the protection of other animals and public health. Therefore, if an animal's medical condition can be reasonably expected to improve as a result of treatment with antimicrobial drugs, and the animal is under a veterinarian's care with an appropriate veterinarian-client-patient relationship, veterinarians have an obligation to offer antimicrobial treatment as a therapeutic option. Veterinarians also have an obligation to actively promote disease prevention efforts, to treat as conservatively as possible, and to explain the potential consequences associated with antimicrobial treatment to animal owners and managers, including the possibility of promoting selection of resistant bacteria. However, the consequences of losing usefulness of an antimicrobial drug that is used as a last resort in humans or animals with resistant bacterial infections might be unacceptable from a public or population health perspective. Veterinarians could therefore face the difficult choice of treating animals with a drug that is less likely to be successful, possibly resulting in prolonged or exacerbated morbidity, to protect the good of society. The Committee recommends that voluntary actions be taken by the veterinary profession to promote conservative use of antimicrobial drugs to minimize the potential adverse effects on animal or human health. The veterinary profession must work to educate all veterinarians about issues related to conservative antimicrobial drug use and

  19. Veterinary Medicine Needs New Green Antimicrobial Drugs

    Directory of Open Access Journals (Sweden)

    Pierre-Louis TOUTAIN

    2016-08-01

    Full Text Available Given that: (1 the worldwide consumption of antimicrobial drugs (AMDs used in food-producing animals will increase over the coming decades; (2 the prudent use of AMDs will not suffice to stem the rise in human antimicrobial resistance (AMR of animal origin; (3 alternatives to AMD use are not available or not implementable, there is an urgent need to develop novel AMDs for food-producing animals. This is not for animal health reasons, but to break the link between human and animal resistomes. In this review we establish the feasibility of developing for veterinary medicine new AMDs, termed green antibiotics, having minimal ecological impact on the animal commensal and environmental microbiomes.We first explain why animal and human commensal microbiota comprise a turnstile exchange, between the human and animal resistomes. We then outline the ideal physico-chemical, pharmacokinetic and pharmacodynamic properties of a veterinary green antibiotic and conclude that they can be developed through a rational screening of currently used AMD classes. The ideal drug will be hydrophilic, of relatively low potency, slow clearance and small volume of distribution. It should be eliminated principally by the kidney as inactive metabolite(s. For oral administration, bioavailability can be enhanced by developing lipophilic pro-drugs. For parenteral administration, slow-release formulations of existing eco-friendly AMDs with a short elimination half-life can be developed. These new eco-friendly veterinary AMDs can be developed from currently used drug classes to provide alternative agents to those currently used in veterinary medicine and mitigate animal contributions to the human AMR problem.

  20. Veterinary Medicine Needs New Green Antimicrobial Drugs.

    Science.gov (United States)

    Toutain, Pierre-Louis; Ferran, Aude A; Bousquet-Melou, Alain; Pelligand, Ludovic; Lees, Peter

    2016-01-01

    Given that: (1) the worldwide consumption of antimicrobial drugs (AMDs) used in food-producing animals will increase over the coming decades; (2) the prudent use of AMDs will not suffice to stem the rise in human antimicrobial resistance (AMR) of animal origin; (3) alternatives to AMD use are not available or not implementable, there is an urgent need to develop novel AMDs for food-producing animals. This is not for animal health reasons, but to break the link between human and animal resistomes. In this review we establish the feasibility of developing for veterinary medicine new AMDs, termed "green antibiotics," having minimal ecological impact on the animal commensal and environmental microbiomes. We first explain why animal and human commensal microbiota comprise a "turnstile" exchange, between the human and animal resistomes. We then outline the ideal physico-chemical, pharmacokinetic, and pharmacodynamic properties of a veterinary green antibiotic and conclude that they can be developed through a rational screening of currently used AMD classes. The ideal drug will be hydrophilic, of relatively low potency, slow clearance and small volume of distribution. It should be eliminated principally by the kidney as inactive metabolite(s). For oral administration, bioavailability can be enhanced by developing lipophilic pro-drugs. For parenteral administration, slow-release formulations of existing eco-friendly AMDs with a short elimination half-life can be developed. These new eco-friendly veterinary AMDs can be developed from currently used drug classes to provide alternative agents to those currently used in veterinary medicine and mitigate animal contributions to the human AMR problem.

  1. 21 CFR 558.6 - Veterinary feed directive drugs.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Veterinary feed directive drugs. 558.6 Section 558.6 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS NEW ANIMAL DRUGS FOR USE IN ANIMAL FEEDS General Provisions...

  2. 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...

  3. Influence of a microemulsion vehicle on cutaneous bioequivalence of a lipophilic model drug assessed by microdialysis and pharmacodynamics

    DEFF Research Database (Denmark)

    Kreilgaard, Mads; Kemme, M J; Burggraaf, J

    2001-01-01

    The aim of the study was to investigate the cutaneous bioequivalence of a lipophilic model drug (lidocaine) applied in a novel topical microemulsion vehicle, compared to a conventional oil-in-water (O/W) emulsion, assessed by a pharmacokinetics microdialysis model and a pharmacodynamic method....

  4. A Bioequivalence Approach for Generic Narrow Therapeutic Index Drugs: Evaluation of the Reference-Scaled Approach and Variability Comparison Criterion

    OpenAIRE

    Jiang, Wenlei; Makhlouf, Fairouz; Schuirmann, Donald J.; Zhang, Xinyuan; Zheng, Nan; Conner, Dale; Yu, Lawrence X.; Lionberger, Robert

    2015-01-01

    Various health communities have expressed concerns regarding whether average bioequivalence (BE) limits (80.00–125.00%) for the 90% confidence interval of the test-to-reference geometric mean ratio are sufficient to ensure therapeutic equivalence between a generic narrow therapeutic index (NTI) drug and its reference listed drug (RLD). Simulations were conducted to investigate the impact of different BE approaches for NTI drugs on study power, including (1) direct tightening of average BE lim...

  5. 21 CFR 320.63 - Retention of bioequivalence samples.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Retention of bioequivalence samples. 320.63... (CONTINUED) DRUGS FOR HUMAN USE BIOAVAILABILITY AND BIOEQUIVALENCE REQUIREMENTS Procedures for Determining the Bioavailability or Bioequivalence of Drug Products § 320.63 Retention of bioequivalence samples...

  6. A Bioequivalence Approach for Generic Narrow Therapeutic Index Drugs: Evaluation of the Reference-Scaled Approach and Variability Comparison Criterion.

    Science.gov (United States)

    Jiang, Wenlei; Makhlouf, Fairouz; Schuirmann, Donald J; Zhang, Xinyuan; Zheng, Nan; Conner, Dale; Yu, Lawrence X; Lionberger, Robert

    2015-07-01

    Various health communities have expressed concerns regarding whether average bioequivalence (BE) limits (80.00-125.00%) for the 90% confidence interval of the test-to-reference geometric mean ratio are sufficient to ensure therapeutic equivalence between a generic narrow therapeutic index (NTI) drug and its reference listed drug (RLD). Simulations were conducted to investigate the impact of different BE approaches for NTI drugs on study power, including (1) direct tightening of average BE limits and (2) a scaled average BE approach where BE limits are tightened based on the RLD's within-subject variability. Addition of a variability comparison (using a one-tailed F test) increased the difficulty for generic NTIs more variable than their corresponding RLDs to demonstrate bioequivalence. Based on these results, the authors evaluate the fully replicated, 2-sequence, 2-treatment, 4-period crossover study design for NTI drugs where the test product demonstrates BE based on a scaled average bioequivalence criterion and a within-subject variability comparison criterion.

  7. Generic-reference and generic-generic bioequivalence of forty-two, randomly-selected, on-market generic products of fourteen immediate-release oral drugs.

    Science.gov (United States)

    Hammami, Muhammad M; De Padua, Sophia J S; Hussein, Rajaa; Al Gaai, Eman; Khodr, Nesrine A; Al-Swayeh, Reem; Alvi, Syed N; Binhashim, Nada

    2017-12-08

    The extents of generic-reference and generic-generic average bioequivalence and intra-subject variation of on-market drug products have not been prospectively studied on a large scale. We assessed bioequivalence of 42 generic products of 14 immediate-release oral drugs with the highest number of generic products on the Saudi market. We conducted 14 four-sequence, randomized, crossover studies on the reference and three randomly-selected generic products of amlodipine, amoxicillin, atenolol, cephalexin, ciprofloxacin, clarithromycin, diclofenac, ibuprofen, fluconazole, metformin, metronidazole, paracetamol, omeprazole, and ranitidine. Geometric mean ratios of maximum concentration (Cmax) and area-under-the-concentration-time-curve, to last measured concentration (AUCT), extrapolated to infinity (AUCI), or truncated to Cmax time of reference product (AUCReftmax) were calculated using non-compartmental method and their 90% confidence intervals (CI) were compared to the 80.00%-125.00% bioequivalence range. Percentages of individual ratios falling outside the ±25% range were also determined. Mean (SD) age and body-mass-index of 700 healthy volunteers (28-80/study) were 32.2 (6.2) years and 24.4 (3.2) kg/m2, respectively. In 42 generic-reference comparisons, 100% of AUCT and AUCI CIs showed bioequivalence, 9.5% of Cmax CIs barely failed to show bioequivalence, and 66.7% of AUCReftmax CIs failed to show bioequivalence/showed bioinequivalence. Adjusting for 6 comparisons, 2.4% of AUCT and AUCI CIs and 21.4% of Cmax CIs failed to show bioequivalence. In 42 generic-generic comparisons, 2.4% of AUCT, AUCI, and Cmax CIs failed to show bioequivalence, and 66.7% of AUCReftmax CIs failed to show bioequivalence/showed bioinequivalence. Adjusting for 6 comparisons, 2.4% of AUCT and AUCI CIs and 14.3% of Cmax CIs failed to show bioequivalence. Average geometric mean ratio deviation from 100% was ≤3.2 and ≤5.4 percentage points for AUCI and Cmax, respectively, in both generic

  8. Residues of veterinary drugs in milk in Brazil

    Directory of Open Access Journals (Sweden)

    Stefani Faro de Novaes

    Full Text Available ABSTRACT: Veterinary drugs are used in dairy cattle management mainly for therapy and prophylaxis of diseases, which chemicals may leave residues in milk. Human exposure and the unintentional consumption of residues of drugs can lead to side effects and development of resistant bacteria, representing a considerable concern to consumer health. This paper presents the occurrence of residues of veterinary drugs in milk from 2009 to 2011 in Brazil, monitored by the Official Program for Analysis of Residues of Veterinary Drugs in Foods of Animal Origin. A total of 961 samples were collected in the retail and evaluated for the main β-lactams, tetracyclines, amphenicol, aminoglycosides, quinolones, sulfonamides and avermectins. Residues of veterinary drugs did not exceed maximum residue limit (MRL; although, there is a considerable use of critically/highly important antimicrobials and avermectins in dairy cows, especially quinolones and tetracyclines. Doxycycline (9% and abamectin (1.6% were detected, even though these substances are not intended to be used in milk producing animals for human consumption. Norfloxacin (15% was observed; although, there are no MRL established, consequently, no residue level should have been detected. No residues of streptomycin, chloramphenicol and β-lactams were confirmed. Milk in Brazil contains low levels of veterinary drugs so that toxicological risk regarding milk consumption could not be considered as a public health concern. However, due to the nature of the samples, which correspond to milk from several farms, it could occur a dilution effect. The absence of MRL established for norfloxacin prevents suitable interpretation of the findings and makes tough the control of these chemical residues in food. Detection of some antimicrobials and avermectins may be linked to extra-label use or noncompliance withdrawal periods suggesting that good veterinary practices are not being followed, since residues of unauthorized

  9. Demonstrating Bioequivalence of Locally Acting Orally Inhaled Drug Products (OIPs): Workshop Summary Report.

    Science.gov (United States)

    Adams, Wallace P; Ahrens, Richard C; Chen, Mei-Ling; Christopher, David; Chowdhury, Badrul A; Conner, Dale P; Dalby, Richard; Fitzgerald, Kevin; Hendeles, Leslie; Hickey, Anthony J; Hochhaus, Günther; Laube, Beth L; Lucas, Paul; Lee, Sau L; Lyapustina, Svetlana; Li, Bing; O'Connor, Dennis; Parikh, Neil; Parkins, David A; Peri, Prasad; Pitcairn, Gary R; Riebe, Michael; Roy, Partha; Shah, Tushar; Singh, Gur Jai Pal; Sharp, Sandra Suarez; Suman, Julie D; Weda, Marjolein; Woodcock, Janet; Yu, Lawrence

    2010-02-01

    This March 2009 Workshop Summary Report was sponsored by Product Quality Research Institute (PQRI) based on a proposal by the Inhalation and Nasal Technology Focus Group (INTFG) of the American Association of Pharmaceutical Scientists (AAPS). Participants from the pharmaceutical industry, academia and regulatory bodies from the United States, Europe, India, and Brazil attended the workshop with the objective of presenting, reviewing, and discussing recommendations for demonstrating bioequivalence (BE) that may be considered in the development of orally inhaled drug products and regulatory guidances for new drug applications (NDAs), abbreviated NDAs (ANDAs), and postapproval changes. The workshop addressed areas related to in vitro approaches to demonstrating BE, biomarker strategies, imaging techniques, in vivo approaches to establishing local delivery equivalence and device design similarity. The workshop presented material that provided a baseline for the current understanding of orally inhaled drug products (OIPs) and identified gaps in knowledge and consensus that, if answered, might allow the design of a robust, streamlined method for the BE assessment of locally acting inhalation drugs. These included the following: (1) cascade impactor (CI) studies are not a good 2 predictor of the pulmonary dose; more detailed studies on in vitro/in vivo correlations (e.g., suitability of CI studies for assessing differences in the regional deposition) are needed; (2) there is a lack of consensus on the appropriate statistical methods for assessing in vitro results; (3) fully validated and standardized imaging methods, while capable of providing information on pulmonary dose and regional deposition, might not be applicable to the BE of inhaled products mainly due to the problems of having access to radiolabeled innovator product; (4) if alternatives to current methods for establishing local delivery BE of OIPs cannot be established, biomarkers (pharmacodynamic or clinical

  10. Prudent Use of Veterinary Drugs: Impact on Safe Animal Products ...

    African Journals Online (AJOL)

    Like any other therapeutic compounds, veterinary drugs are used to alleviate diseases in animals as either therapeutic or prophylactic compounds for specific disease entities. They can also be used as production aids in food producing animals to increase market sale of these animals whereby the producers save on the ...

  11. Assessment of veterinary drug use and determination of ...

    African Journals Online (AJOL)

    A cross-sectional study was conducted between October 2009 and January 2010 to assess veterinary drug usage by broiler chicken farmers and to determine antimicrobial residues in broiler meat in Urban district, Zanzibar, Tanzania. Fifty five smallholder farmers were interviewed on types of antimicrobials, reasons for use, ...

  12. In vitro bioequivalence approach for a locally acting gastrointestinal drug: lanthanum carbonate.

    Science.gov (United States)

    Yang, Yongsheng; Shah, Rakhi B; Yu, Lawrence X; Khan, Mansoor A

    2013-02-04

    A conventional human pharmacokinetic (PK) in vivo study is often considered as the "gold standard" to determine bioequivalence (BE) of drug products. However, this BE approach is not always applicable to the products not intended to be delivered into the systemic circulation. For locally acting gastrointestinal (GI) products, well designed in vitro approaches might be more practical in that they are able not only to qualitatively predict the presence of the active substance at the site of action but also to specifically assess the performance of the active substance. For example, lanthanum carbonate chewable tablet, a locally acting GI phosphate binder when orally administrated, can release free lanthanum ions in the acid environment of the upper GI tract. The lanthanum ions directly reach the site of action to bind with dietary phosphate released from food to form highly insoluble lanthanum-phosphate complexes. This prevents the absorption of phosphate consequently reducing the serum phosphate. Thus, using a conventional PK approach to demonstrate BE is meaningless since plasma levels are not relevant for local efficacy in the GI tract. Additionally the bioavailability of lanthanum carbonate is less than 0.002%, and therefore, the PK approach is not feasible. Therefore, an alternative assessment method is required. This paper presents an in vitro approach that can be used in lieu of PK or clinical studies to determine the BE of lanthanum carbonate chewable tablets. It is hoped that this information can be used to finalize an in vitro guidance for BE studies of lanthanum carbonate chewable tablets as well as to assist with "in vivo" biowaiver decision making. The scientific information might be useful to the pharmaceutical industry for the purpose of planning and designing future BE studies.

  13. A comparative analysis of biopharmaceutics classification system and biopharmaceutics drug disposition classification system: a cross-sectional survey with 500 bioequivalence studies.

    Science.gov (United States)

    Cristofoletti, Rodrigo; Chiann, Chang; Dressman, Jennifer B; Storpirtis, Silvia

    2013-09-01

    Although policies of waiving bioequivalence studies are part of the legal framework of various regulatory agencies, there is no harmonization with regard to extension of the biowaiver to drugs other than those with high solubility and high permeability, nor is there any consensus or official endorsement of the biopharmaceutics drug disposition classification system (BDDCS). To better understand the applicability of the biowaiver, we carried out a cross-sectional survey to estimate the relative risk of obtaining nonbioequivalent (non-BE) or bioinequivalent (BIE) results for drug products containing drugs belonging to each of the biopharmaceutics classification system (BCS) and BDDCS classes. Five hundred bioequivalence studies were randomly sampled from a database of the Brazilian Health Surveillance Agency (ANVISA). The drugs were classified according to the BCS and BDDCS, to evaluate how characteristics related to drug and dosage form influence the outcome of bioequivalence studies. The relative risk of obtaining a non-BE result was approximately four times lower for drugs in classes 1 and 3 of BCS or BDDCS when compared with class 2 drugs. Thus, it seems that the final outcome of a bioequivalence study is strongly influenced by the solubility of the drug, but not by its intestinal permeability or extent of metabolism. Copyright © 2013 Wiley Periodicals, Inc.

  14. Saliva Versus Plasma Bioequivalence of Azithromycin in Humans: Validation of Class I Drugs of the Salivary Excretion Classification System.

    Science.gov (United States)

    Idkaidek, Nasir; Arafat, Tawfiq; Hamadi, Hazim; Hamadi, Salim; Al-Adham, Ibrahim

    2017-03-01

    The aim of this study was to compare human pharmacokinetics and bioequivalence metrics in saliva versus plasma for azithromycin as a model class I drug of the Salivary Excretion Classification System (SECS). A pilot, open-label, two-way crossover bioequivalence study was done, and involved a single 500-mg oral dose of azithromycin given to eight healthy subjects under fasting conditions, followed by a 3-week washout period. Blood and unstimulated saliva samples were collected over 72 h and deep frozen until analysis by a validated liquid chromatography with mass spectroscopy method. The pharmacokinetic parameters and bioequivalence metrics of azithromycin were calculated by non-compartment analysis using WinNonlin V5.2. Descriptive statistics and dimensional analysis of the pharmacokinetic parameters of azithromycin were performed using Microsoft Excel. PK-Sim V5.6 was used to estimate the effective intestinal permeability of azithromycin. No statistical differences were shown in area under the concentration curves to 72 h (AUC 0-72 ), maximum measured concentration (C max ) and time to maximum concentration (T max ) between test and reference azithromycin products (P > 0.05) in the saliva matrix and in the plasma matrix. Due to the high intra-subject variability and low sample size of this pilot study, the 90% confidence intervals of AUC 0-72 and C max did not fall within the acceptance range (80-125%). However, saliva levels were higher than that of plasma, with a longer salivary T max . The mean saliva/plasma concentration of test and reference were 2.29 and 2.33, respectively. The mean ± standard deviation ratios of saliva/plasma of AUC 0-72 , C max and T max for test were 2.65 ± 1.59, 1.51 ± 0.49 and 1.85 ± 1.4, while for the reference product they were 3.37 ± 2.20, 1.57 ± 0.77 and 2.6 ± 1.27, respectively. A good correlation of R = 0.87 between plasma and saliva concentrations for both test and reference products was also observed

  15. Health concerns and management of select veterinary drug residues.

    Science.gov (United States)

    Baynes, Ronald E; Dedonder, Keith; Kissell, Lindsey; Mzyk, Danielle; Marmulak, Tara; Smith, Geof; Tell, Lisa; Gehring, Ronette; Davis, Jennifer; Riviere, Jim E

    2016-02-01

    The aim of this manuscript is to review the potential adverse health effects in humans if exposed to residues of selected veterinary drugs used in food-producing animals. Our other objectives are to briefly inform the reader of why many of these drugs are or were approved for use in livestock production and how drug residues can be mitigated for these drugs. The selected drugs include several antimicrobials, beta agonists, and phenylbutazone. The antimicrobials continue to be of regulatory concern not only because of their acute adverse effects but also because their use as growth promoters have been linked to antimicrobial resistance. Furthermore, nitroimidazoles and arsenicals are no longer approved for use in food animals in most jurisdictions. In recent years, the risk assessment and risk management of beta agonists, have been the focus of national and international agencies and this manuscript attempts to review the pharmacology of these drugs and regulatory challenges. Several of the drugs selected for this review can cause noncancer effects (e.g., penicillins) and others are potential carcinogens (e.g., nitroimidazoles). This review also focuses on how regulatory and independent organizations manage the risk of these veterinary drugs based on data from human health risk assessments. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. [Toxicological study of three veterinary drugs on Eisenia foetida].

    Science.gov (United States)

    Qu, Mengmeng; Xu, Yun; Chen, Haigang; Li, Zhaoli; Sun, Liwei; Xu, Dijin; Kong, Zhiming; Sugiura, Norio

    2005-06-01

    By the methods of acute toxicity test and single cell gel electrophoresis (comet assay), this paper evaluated the toxicological effects of three veterinary drugs olaquindox, arsanilic acid and oxytetracycline on earthworm (Eisenia foetida) coelomocytes in vivo. The results of acute toxicity test showed that only the highest dose of olaquidox caused the death of some earthworms, and none of the test drugs had any effects on earthworm at their environmentally relevant concentrations. The comet assay indicated that arsanilic acid had no genotoxicity to earthworm, while olaquindox and oxytetracycline induced significant DNA damage in earthworm coelomocytes (P .01).

  17. Bioequivalence Methodologies for Topical Drug Products: In Vitro and Ex Vivo Studies with a Corticosteroid and an Anti-Fungal Drug.

    Science.gov (United States)

    Leal, Leila Bastos; Cordery, Sarah F; Delgado-Charro, M Begoña; Bunge, Annette L; Guy, Richard H

    2017-04-01

    To examine whether in vitro and ex vivo measurements of topical drug product performance correlate with in vivo outcomes, such that more efficient experimental approaches can be reliably and reproducibly used to establish (in)equivalence between formulations for skin application. In vitro drug release through artificial membranes, and drug penetration into porcine skin ex vivo, were compared with published human in vivo studies. Two betamethasone valerate (BMV) formulations, and three marketed econazole nitrate (EN) creams were assessed. For BMV, the stratum corneum (SC) uptake of drug in 6 h closely matched data observed in vivo in humans, and distinguished between inequivalent formulations. SC uptake of EN from the 3 creams mirrored the in vivo equivalence in man (both clinically and via similar tape-stripping experiments). However, EN clearance from SC ex vivo did not parallel that in vivo, presumably due to the absence of a functioning microcirculation. In vitro release of BMV from the different formulations did not overlap with either ex vivo or in vivo tape-stripping data whereas, for EN, a good correlation was observed. No measurable permeation of either BMV or EN was detected in a 6-h in vitro skin penetration experiment. In vitro and ex vivo methods for topical bioequivalence determination can show correlation with in vivo outcomes. However, these surrogates have understandable limitations. A "one-size-fits-all" approach for topical bioequivalence evaluation may not always be successful, therefore, and the judicious use of complementary methods may prove a more effective and reliable strategy.

  18. Sex Effect on Average Bioequivalence.

    Science.gov (United States)

    Ibarra, Manuel; Vázquez, Marta; Fagiolino, Pietro

    2017-01-01

    Generic formulations are by far the most prescribed drugs. This scenario is highly beneficial for society because medication expenses are significantly reduced after expiration of the exclusivity period conceded to the branded name drug. Correspondingly, these formulations must be adequately evaluated to avoid drug inefficacy and toxicity in the overall patient population. Bioequivalence studies are the only in vivo evaluation that a generic drug must overcome to reach the market. These clinical trials have not been exempt from underrepresentation of female subjects and a lack of sex-based analysis. Frequently, conclusions obtained in men are extrapolated to women. Furthermore, the obtained results are not analyzed to determine sex differences. The aim of this study was to discuss the effect that male and female differences in gastrointestinal physiology can have on bioequivalence conclusions and to show why a sex-based analysis must be conducted in these studies to improve the evaluation of generic drugs. This discussion was based on observed sex differences in product bioavailability discrimination (sex-by-formulation interaction) and on residual variability through an analysis of average bioequivalence data previously reported by other researchers and data collected by our center. Bioequivalence studies of oral formulations, with a 2-period, 2-sequence, 2-treatment random crossover design performed in healthy subjects with at least 6 subjects of each sex, were included. In addition, the bioequivalence conclusion that would have been reached in each study if performed with only 1 sex was estimated. The data reveal that differences in both product bioavailability discrimination and residual variability occur with a significant incidence in bioequivalence studies. In either Cmax or AUC, a significant sex-by-formulation interaction was present in 1 of 3 reviewed studies, whereas differences in residual variability between sexes were significant for >50% of studies

  19. Effect of Truncating AUC at 12, 24 and 48 hr When Evaluating the Bioequivalence of Drugs with a Long Half-Life.

    Science.gov (United States)

    Moreno, Isabel; Ochoa, Dolores; Román, Manuel; Cabaleiro, Teresa; Abad-Santos, Francisco

    2016-01-01

    Bioequivalence studies of drugs with a long half-life require long periods of time for pharmacokinetic sampling. The latest update of the European guideline allows the area under the curve (AUC) truncated at 72 hr to be used as an alternative to AUC0-t as the primary parameter. The objective of this study was to evaluate the effect of truncating the AUC at 48, 24 and 12 hr on the acceptance of the bioequivalence criterion as compared with truncation at 72 hr in bioequivalence trials. The effect of truncated AUC on the within-individual coefficient of variation (CVw) and on the ratio of the formulations was also analysed. Twenty-eight drugs were selected from bioequivalence trials. Pharmacokinetic data were analysed using WinNonLin 2.0 based on the trapezoidal method. Analysis of variance (ANOVA) was performed to obtain the ratios and 90% confidence intervals for AUC at different time-points. The degree of agreement of AUC0-72 in relation to AUC0-48 and AUC0-24, according to the Landis and Koch classification, was 'almost perfect'. Statistically significant differences were observed when the CVw of AUC truncated at 72, 48 and 24 hr was compared with the CVw of AUC0-12. There were no statistically significant differences in the AUC ratio at any time-point. Compared to AUC0-72, Pearson's correlation coefficient for mean AUC, AUC ratio and AUC CVw was worse for AUC0-12 than AUC0-24 or AUC0-48. These preliminary results could suggest that AUC truncation at 24 or 48 hr is adequate to determine whether two formulations are bioequivalent. © 2015 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  20. Investigation of bioequivalence of a new fixed-dose combination of nifedipine and candesartan with the corresponding loose combination as well as the drug-drug interaction potential between both drugs under fasting conditions.

    Science.gov (United States)

    Brendel, Erich; Weimann, Boris; Dietrich, Hartmut; Froede, Christoph; Thomas, Dirk

    2013-09-01

    To determine the bioequivalence of a nifedipine and candesartan fixed-dose combination (FDC) with the corresponding loose combination, and to investigate the pharmacokinetic drug-drug interaction potential between both drugs. 49 healthy, white, male subjects received: 60 mg nifedipine and 32 mg candesartan FDC, the loose combination of 60 mg nifedipine GITS and 32 mg candesartan, 60 mg nifedipine GITS alone, or 32 mg candesartan alone in a randomized, non-blinded, 4-period, 4-way crossover design with each dosing following overnight fasting. Treatment periods were separated by washout periods of ≥ 5 days. Plasma samples were collected for 48 hours after dosing and assayed using a validated LC-MS/MS method. Bioequivalence between the FDC and the loose combination as well as the impact of combined treatment with both drugs on candesartan pharmacokinetics was evaluated in 47 subjects, while the corresponding impact of treatment with both drugs on nifedipine pharmacokinetics was assessed in 46 patients. For AUC(0-tlast) and Cmax the 90% confidence intervals (CIs) for the ratios of the FDC vs. the corresponding loose combination were within the acceptance range for bioequivalence of 80 - 125%. When comparing AUC(0-tlast) and Cmax of nifedipine and candesartan after dosing with the loose combination vs. each drug alone, the 90% CIs remained within the range of 80 - 125% indicating the absence of a clinically relevant pharmacokinetic drug-drug interaction. Nifedipine and candesartan as well as the combinations were well tolerated. The FDC containing 60 mg nifedipine and 32 mg candesartan was bioequivalent to the corresponding loose combination following single oral doses under fasting conditions. No clinically relevant pharmacokinetic drug-drug interaction between nifedipine and candesartan was observed.

  1. Complement activation as a bioequivalence issue relevant to the development of generic liposomes and other nanoparticulate drugs

    Energy Technology Data Exchange (ETDEWEB)

    Szebeni, Janos, E-mail: jszebeni2@gmail.com [Nanomedicine Research and Education Center, Semmelweis University, Budapest & SeroScience Ltd, Budapest (Hungary); Storm, Gert [Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Utrecht (Netherlands)

    2015-12-18

    Liposomes are known to activate the complement (C) system, which can lead in vivo to a hypersensitivity syndrome called C activation-related pseudoallergy (CARPA). CARPA has been getting increasing attention as a safety risk of i.v. therapy with liposomes, whose testing is now recommended in bioequivalence evaluations of generic liposomal drug candidates. This review highlights the adverse consequences of C activation, the unique symptoms of CARPA triggered by essentially all i.v. administered liposomal drugs, and the various features of vesicles influencing this adverse immune effect. For the case of Doxil, we also address the mechanism of C activation and the opsonization vs. long circulation (stealth) paradox. In reviewing the methods of assessing C activation and CARPA, we delineate the most sensitive porcine model and an algorithm for stepwise evaluation of the CARPA risk of i.v. liposomes, which are proposed for standardization for preclinical toxicology evaluation of liposomal and other nanoparticulate drug candidates. - Highlights: • Outlining of difficulties in generic development of liposomal drugs. • New regulatory requirements to evaluate CARPA in preclinical studies. • Review of complement activation by liposomes and its adverse consequences (CARPA). • Assays of C activation in vitro and CARPA in vivo, with the porcine test in focus. • Decision tree how to handle the risk of CARPA assessed by a battery of tests.

  2. Computer simulations of bioequivalence trials: selection of design and analyte in BCS drugs with first-pass hepatic metabolism: linear kinetics (I).

    Science.gov (United States)

    Fernández-Teruel, Carlos; Nalda Molina, Ricardo; González-Alvarez, Isabel; Navarro-Fontestad, Carmen; García-Arieta, Alfredo; Casabó, Vicente G; Bermejo, Marival

    2009-01-31

    Modeling and simulation approaches are useful tools to assess the potential outcome of different scenarios in bioequivalence studies. The aim of this study is to propose a new and improved semi-physiological model for bioequivalence trial simulations and apply it for all BCS (Biopharmaceutic Classification System) drug classes with non-saturated first-pass hepatic metabolism. The semi-physiological model was developed in NONMEM VI to simulate bioequivalence trials. Parent drug and metabolite levels for both reference and test were simulated. Eight types of drugs (with high or low permeability and high or low solubility (class I to IV) and high or low intrinsic clearance) were considered in two variability scenarios (high-low) and in six test products of decreasing biopharmaceutic quality. The scenarios were tested in single dose and steady state studies. In case of drugs with non-saturated hepatic first-pass effect (and no gut-wall metabolism) the parent drug is usually the most sensitive analyte and the single dose design is usually the most sensitive study design to detect the worsening of the biopharmaceutic quality of the test formulation. The only exception to this general conclusion was observed in class III drugs (high solubility, low permeability) with low intrinsic clearance for which the parent drug C(max) ratio in steady state shows higher sensitivity followed by the metabolite C(max) ratio in single dose. This exceptional behaviour is caused by a limited operative absorption time (or absorption window) in class III drugs that precludes complete absorption and produces a non-linear absorption. Therefore, it can be concluded that the metabolite does not need to be measured if the drug has no gut-wall metabolism and shows linear pharmacokinetics. Interestingly, a steady state study should be conducted in this exceptional case to compare with the highest possible sensitivity. Metabolite data in most of the scenarios either shows less sensitivity to the

  3. Survey of Veterinary Drug Residues in Raw Milk in Hebei Province, China.

    Science.gov (United States)

    Han, Rong-Wei; Yu, Zhong-Na; Zhen, Tian-Yuan; Wang, Jun

    2017-10-17

    The objective of this study was to investigate the occurrence of veterinary drug residues in raw milk from Hebei, the second-largest dairy production province in the People's Republic of China. A total of 192 raw milk samples were collected from 64 milk stations in seven districts. Twenty-eight veterinary drug residues were analyzed by ultraperformance liquid chromatography with tandem mass spectrometry based on a China National Standard. Raw milk samples with multiple residues of veterinary drugs were not found in the present study. Residues of four veterinary drugs, penicillin G, sulfacetamide, trimethoprim, and lincomycin, were detected in 12 (6.25%) raw milk samples, with detection ratios of 1.04, 0.52, 3.13, and 1.56%, respectively. All veterinary drug residues detected were under the maximum residue levels as regulated by China, the European Union, the United States, and the Codex Alimentarius Commission. In general, raw milk from Hebei province was considered relatively safe for human consumption because of the low prevalence of veterinary drug residues. However, stringent control measurements for veterinary drug residues in raw milk are required because some veterinary drugs were detected in milk from some areas of Hebei province.

  4. Stability during cooking of anthelmintic veterinary drug residues in beef.

    Science.gov (United States)

    Cooper, K M; Whelan, M; Danaher, M; Kennedy, D G

    2011-02-01

    Anthelmintic drugs are widely used for treatment of parasitic worms in livestock, but little is known about the stability of their residues in food under conventional cooking conditions. As part of the European Commission-funded research project ProSafeBeef, cattle were medicated with commercially available anthelmintic preparations, comprising 11 active ingredients (corresponding to 21 marker residues). Incurred meat and liver were cooked by roasting (40 min at 190°C) or shallow frying (muscle 8-12 min, liver 14-19 min) in a domestic kitchen. Raw and cooked tissues and expressed juices were analysed using a novel multi-residue dispersive solid-phase extraction method (QuEChERS) coupled with ultra-performance liquid chromatography-tandem mass spectrometry. After correction for sample weight changes during cooking, no major losses were observed for residues of oxyclozanide, clorsulon, closantel, ivermectin, albendazole, mebendazole or fenbendazole. However, significant losses were observed for nitroxynil (78% in fried muscle, 96% in roast muscle), levamisole (11% in fried muscle, 42% in fried liver), rafoxanide (17% in fried muscle, 18% in roast muscle) and triclabendazole (23% in fried liver, 47% in roast muscle). Migration of residues from muscle into expressed cooking juices varied between drugs, constituting 0% to 17% (levamisole) of total residues remaining after cooking. With the exception of nitroxynil, residues of anthelmintic drugs were generally resistant to degradation during roasting and shallow frying. Conventional cooking cannot, therefore, be considered a safeguard against ingestion of residues of anthelmintic veterinary drugs in beef.

  5. 21 CFR 320.22 - Criteria for waiver of evidence of in vivo bioavailability or bioequivalence.

    Science.gov (United States)

    2010-04-01

    ... bioavailability or bioequivalence. 320.22 Section 320.22 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE BIOAVAILABILITY AND BIOEQUIVALENCE REQUIREMENTS Procedures for Determining the Bioavailability or Bioequivalence of Drug Products § 320.22...

  6. 21 CFR 320.24 - Types of evidence to measure bioavailability or establish bioequivalence.

    Science.gov (United States)

    2010-04-01

    ... establish bioequivalence. 320.24 Section 320.24 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE BIOAVAILABILITY AND BIOEQUIVALENCE REQUIREMENTS Procedures for Determining the Bioavailability or Bioequivalence of Drug Products § 320.24 Types of evidence...

  7. 21 CFR 320.36 - Requirements for maintenance of records of bioequivalence testing.

    Science.gov (United States)

    2010-04-01

    ... bioequivalence testing. 320.36 Section 320.36 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE BIOAVAILABILITY AND BIOEQUIVALENCE REQUIREMENTS Procedures for Determining the Bioavailability or Bioequivalence of Drug Products § 320.36 Requirements for...

  8. 21 CFR 320.23 - Basis for measuring in vivo bioavailability or demonstrating bioequivalence.

    Science.gov (United States)

    2010-04-01

    ... demonstrating bioequivalence. 320.23 Section 320.23 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE BIOAVAILABILITY AND BIOEQUIVALENCE REQUIREMENTS Procedures for Determining the Bioavailability or Bioequivalence of Drug Products § 320.23 Basis for...

  9. 21 CFR 320.29 - Analytical methods for an in vivo bioavailability or bioequivalence study.

    Science.gov (United States)

    2010-04-01

    ... or bioequivalence study. 320.29 Section 320.29 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE BIOAVAILABILITY AND BIOEQUIVALENCE REQUIREMENTS Procedures for Determining the Bioavailability or Bioequivalence of Drug Products § 320.29...

  10. Implementation of a reference-scaled average bioequivalence approach for highly variable generic drug products of agomelatine in Chinese subjects

    Directory of Open Access Journals (Sweden)

    Fang Tang

    2016-01-01

    Full Text Available The aim of this study was to apply the reference-scaled average bioequivalence (RSABE approach to evaluate the bioequivalence of 2 formulations of agomelatine, and to investigate the pharmacokinetic properties of agomelatine in Chinese healthy male subjects. This was performed in a single-dose, randomized-sequence, open-label, four-way crossover study with a one-day washout period between doses. Healthy Chinese males were randomly assigned to receive 25 mg of either the test or reference formulation. The formulations were considered bioequivalent if 90% confidence intervals (CIs for the log-transformed ratios and ratio of geometric means (GMR of AUC and Cmax of agomelatine were within the predetermined bioequivalence range based on RSABE method. Results showed that both of the 90% CIs for the log-transformed ratios of AUC and Cmax of 7-desmethyl-agomelatine and 3-hydroxy-agomelatine were within the predetermined bioequivalence range. The 90% CIs for natural log-transformed ratios of Cmax, AUC0–t and AUC0–∞ of agomelatine (104.42–139.86, 101.33–123.83 and 97.90–117.94 were within the RSABE acceptance limits, and 3-hydroxy-agomelatine (105.55–123.03, 101.95–109.10 and 101.72–108.70 and 7-desmethyl-agomelatine (104.50–125.23, 102.36–111.50 and 101.62–110.64 were within the FDA bioequivalence definition intervals (0.80–1.25 for AUC and 0.75–1.33 for Cmax. The RSABE approach was successful in evaluating the bioequivalence of these two formulations.

  11. Current regulatory approaches of bioequivalence testing.

    Science.gov (United States)

    Karalis, Vangelis; Macheras, Panos

    2012-08-01

    Nowadays, reducing medication costs is vital for health care agencies. Prescription of generic drug products can help lower these expenses. A generally accepted assumption is that therapeutic equivalence, between a generic and a brand-name medication, can be claimed if bioequivalence is demonstrated. This article reviews the current regulatory procedures on bioequivalence testing. Special focus is placed on the guidelines recommended by the European Medicines Agency and the US Food and Drug administration. The authors also describe the evolution of these issues and the alternatives proposed in the literature. Defining bioequivalence, as the condition of no significant differences in the extent and rate of absorption between the generic and the brand-name medication, sounds simple. However, the scientific and regulatory basis of bioequivalence appears rather complicated in practice. Even though the regulatory authorities have elucidated many issues, several aspects of bioequivalence assessment are still unresolved. Examples, of these open questions, in bioequivalence, include the assessment of complex drugs, such as biologics and iron-carbohydrates, the assessment of immunosuppressive agents as well as the role that pharmacogenomics plays in bioequivalence.

  12. 78 FR 73199 - Draft Guidance for Industry on Bioequivalence Studies With Pharmacokinetic Endpoints for Drugs...

    Science.gov (United States)

    2013-12-05

    ... administered drug products in which reliance on systemic exposure measures is suitable for documenting BE. The... one self-addressed adhesive label to assist that office in processing your requests. See the... administered drug products in which reliance on systemic exposure measures is suitable for documenting BE (e.g...

  13. Flexing the PECs: Predicting environmental concentrations of veterinary drugs in Canadian agricultural soils.

    Science.gov (United States)

    Kullik, Sigrun A; Belknap, Andrew M

    2017-03-01

    Veterinary drugs administered to food animals primarily enter ecosystems through the application of livestock waste to agricultural land. Although veterinary drugs are essential for protecting animal health, their entry into the environment may pose a risk for nontarget organisms. A means to predict environmental concentrations of new veterinary drug ingredients in soil is required to assess their environmental fate, distribution, and potential effects. The Canadian predicted environmental concentrations in soil (PECsoil) for new veterinary drug ingredients for use in intensively reared animals is based on the approach currently used by the European Medicines Agency for VICH Phase I environmental assessments. The calculation for the European Medicines Agency PECsoil can be adapted to account for regional animal husbandry and land use practices. Canadian agricultural practices for intensively reared cattle, pigs, and poultry differ substantially from those in the European Union. The development of PECsoil default values and livestock categories representative of typical Canadian animal production methods and nutrient management practices culminates several years of research and an extensive survey and analysis of the scientific literature, Canadian agricultural statistics, national and provincial management recommendations, veterinary product databases, and producers. A PECsoil can be used to rapidly identify new veterinary drugs intended for intensive livestock production that should undergo targeted ecotoxicity and fate testing. The Canadian PECsoil model is readily available, transparent, and requires minimal inputs to generate a screening level environmental assessment for veterinary drugs that can be refined if additional data are available. PECsoil values for a hypothetical veterinary drug dosage regimen are presented and discussed in an international context. Integr Environ Assess Manag 2017;13:331-341. © 2016 Her Majesty the Queen in Right of Canada

  14. Comparative assessment of saliva and plasma for drug bioavailability and bioequivalence studies in humans

    Directory of Open Access Journals (Sweden)

    Nasir M. Idkaidek

    2017-07-01

    Conclusion: Our results suggest that there is a potential in BA/BE studies for saliva to be considered as a surrogate for plasma concentration, which goes along with drug regulations. The use of saliva instead of plasma in such studies makes them non-invasive, easy and with a lower clinical burden.

  15. Large-scale cross-species chemogenomic platform proposes a new drug discovery strategy of veterinary drug from herbal medicines.

    Science.gov (United States)

    Huang, Chao; Yang, Yang; Chen, Xuetong; Wang, Chao; Li, Yan; Zheng, Chunli; Wang, Yonghua

    2017-01-01

    Veterinary Herbal Medicine (VHM) is a comprehensive, current, and informative discipline on the utilization of herbs in veterinary practice. Driven by chemistry but progressively directed by pharmacology and the clinical sciences, drug research has contributed more to address the needs for innovative veterinary medicine for curing animal diseases. However, research into veterinary medicine of vegetal origin in the pharmaceutical industry has reduced, owing to questions such as the short of compatibility of traditional natural-product extract libraries with high-throughput screening. Here, we present a cross-species chemogenomic screening platform to dissect the genetic basis of multifactorial diseases and to determine the most suitable points of attack for future veterinary medicines, thereby increasing the number of treatment options. First, based on critically examined pharmacology and text mining, we build a cross-species drug-likeness evaluation approach to screen the lead compounds in veterinary medicines. Second, a specific cross-species target prediction model is developed to infer drug-target connections, with the purpose of understanding how drugs work on the specific targets. Third, we focus on exploring the multiple targets interference effects of veterinary medicines by heterogeneous network convergence and modularization analysis. Finally, we manually integrate a disease pathway to test whether the cross-species chemogenomic platform could uncover the active mechanism of veterinary medicine, which is exemplified by a specific network module. We believe the proposed cross-species chemogenomic platform allows for the systematization of current and traditional knowledge of veterinary medicine and, importantly, for the application of this emerging body of knowledge to the development of new drugs for animal diseases.

  16. Large-scale cross-species chemogenomic platform proposes a new drug discovery strategy of veterinary drug from herbal medicines.

    Directory of Open Access Journals (Sweden)

    Chao Huang

    Full Text Available Veterinary Herbal Medicine (VHM is a comprehensive, current, and informative discipline on the utilization of herbs in veterinary practice. Driven by chemistry but progressively directed by pharmacology and the clinical sciences, drug research has contributed more to address the needs for innovative veterinary medicine for curing animal diseases. However, research into veterinary medicine of vegetal origin in the pharmaceutical industry has reduced, owing to questions such as the short of compatibility of traditional natural-product extract libraries with high-throughput screening. Here, we present a cross-species chemogenomic screening platform to dissect the genetic basis of multifactorial diseases and to determine the most suitable points of attack for future veterinary medicines, thereby increasing the number of treatment options. First, based on critically examined pharmacology and text mining, we build a cross-species drug-likeness evaluation approach to screen the lead compounds in veterinary medicines. Second, a specific cross-species target prediction model is developed to infer drug-target connections, with the purpose of understanding how drugs work on the specific targets. Third, we focus on exploring the multiple targets interference effects of veterinary medicines by heterogeneous network convergence and modularization analysis. Finally, we manually integrate a disease pathway to test whether the cross-species chemogenomic platform could uncover the active mechanism of veterinary medicine, which is exemplified by a specific network module. We believe the proposed cross-species chemogenomic platform allows for the systematization of current and traditional knowledge of veterinary medicine and, importantly, for the application of this emerging body of knowledge to the development of new drugs for animal diseases.

  17. Regulatory verification on safe use of cytotoxic drugs in veterinary clinics and animal hospitals.

    Science.gov (United States)

    Fung, V; Seneviratne, M

    2016-11-01

    Veterinarians are increasingly being asked to provide chemotherapy for veterinary patients. However, chemotherapy agents have cytotoxic effects that can pose a health risk to workers from exposure. There are no published studies examining cytotoxic drug (CTD) contamination in veterinary practices in Australia. CTD use at 13 veterinary clinics and animal hospitals across New South Wales (NSW) was verified for compliance with Work, Health and Safety (WHS) legislation on the effectiveness of exposure control measures. Surface swab sampling was performed to detect the restricted carcinogen cyclophosphamide and seven other CTD. A total of 73 surface swab samples were collected from nine locations associated with CTD delivery, storage, treatment and waste disposal at four veterinary practices, with repeat sampling at two veterinary practices. Compliance with WHS legislation for systematic chemical management, including procedures for safe use of carcinogens, in veterinary practices was high: 4 of the 10 key clauses in WHS chemical management were complied with at all 13 verified workplaces. Surface contamination was detected in three locations, with levels of CTD contaminants ranging from 3.54 to 89 ng per sample. Results showed that, in general, there were safe systems in place to work with CTD in the veterinary practices that were verified in NSW. Areas for improvement were mainly in administrative measures related to hazardous chemical management. Particular attention should be given to raising awareness of the intrinsic hazards of CTD, through training and hazard information provision to staff. © 2016 Australian Veterinary Association.

  18. Veterinary drug prescriptions: to what extent do pet owners comply ...

    African Journals Online (AJOL)

    Separate questionnaires were designed for pet owners (clients) and veterinarians to ascertain the existence and extent of noncompliance in veterinary practice in lbadan and to elucidate the influence of such factors as logistics, education, economy, attitudes and veterinarian/client relationship on non-compliance. Analyses ...

  19. Development of Analytical Method and Monitoring of Veterinary Drug Residues in Korean Animal Products.

    Science.gov (United States)

    Song, Jae-Sang; Park, Su-Jeong; Choi, Jung-Yun; Kim, Jin-Sook; Kang, Myung-Hee; Choi, Bo-Kyung; Hur, Sun Jin

    2016-01-01

    This study was conducted to determine the residual amount of veterinary drugs such as meloxicam, flunixin, and tulathromycin in animal products (beef, pork, horsemeat, and milk). Veterinary drugs have been widely used in the rearing of livestock to prevent and treat diseases. A total of 152 samples were purchased from markets located in major Korean cities (Seoul, Busan, Incheon, Daegu, Daejeon, Gwangju, Ulsan and Jeju), including Jeju. Veterinary drugs were analyzed by liquid chromatography-tandem mass spectrometry according to the Korean Food Standards Code. The resulting data, which are located within 70-120% of recovery range and less than 20% of relative standard deviations, are in compliance with the criteria of CODEX. A total of five veterinary drugs were detected in 152 samples, giving a detection rate of approximately 3.3%; and no food source violated the guideline values. Our result indicated that most of the veterinary drug residues in animal products were below the maximum residue limits specified in Korea.

  20. Development of Analytical Method and Monitoring of Veterinary Drug Residues in Korean Animal Products

    Science.gov (United States)

    Song, Jae-Sang; Park, Su-Jeong; Choi, Jung-Yun; Kim, Jin-Sook; Kang, Myung-Hee; Choi, Bo-Kyung

    2016-01-01

    This study was conducted to determine the residual amount of veterinary drugs such as meloxicam, flunixin, and tulathromycin in animal products (beef, pork, horsemeat, and milk). Veterinary drugs have been widely used in the rearing of livestock to prevent and treat diseases. A total of 152 samples were purchased from markets located in major Korean cities (Seoul, Busan, Incheon, Daegu, Daejeon, Gwangju, Ulsan and Jeju), including Jeju. Veterinary drugs were analyzed by liquid chromatography-tandem mass spectrometry according to the Korean Food Standards Code. The resulting data, which are located within 70-120% of recovery range and less than 20% of relative standard deviations, are in compliance with the criteria of CODEX. A total of five veterinary drugs were detected in 152 samples, giving a detection rate of approximately 3.3%; and no food source violated the guideline values. Our result indicated that most of the veterinary drug residues in animal products were below the maximum residue limits specified in Korea. PMID:27433102

  1. Milk quality parameters associated with the occurrence of veterinary drug residues in bulk tank milk

    Directory of Open Access Journals (Sweden)

    Lidia Cristina Almeida Picinin

    Full Text Available ABSTRACT Veterinary drug residues in bulk tank milk are important to all sectors of the dairy chain because they are one of the major factors which determine the safety of the final product. This study attempted to identify milk quality parameters that are associated with the occurrence of veterinary drug residues using multivariate principal component analysis (PCA. A total of 132 raw milk samples were collected from 45 dairy farms in the state of Minas Gerais - Brazil and analyzed for 42 analytes, including pyrethroids, macrocyclic lactones and antibacterials, using liquid chromatography coupled with mass spectrometry in tandem mode and gas chromatography with electron capture detection. Out of the 132 milk samples, 40 samples tested positive for at least one analyte (above the detection limit. The milk parameters associated with the antimicrobial residues by confirmatory tests were lactose and nonfat concentrations, as revealed by PCA. This analysis showed that fat and total solid concentrations, as well as the somatic cell and total bacteria counts were associated with macrocyclic lactone residues in bulk tank milk. A PCA assessing pyrethroid residues in bulk tank milk revealed that the lactose and nonfat solid concentrations and titratable acidity were inversely associated with these residues. Thus, the data analysis indicated that the veterinary drug residues were associated with certain milk quality parameters that can be used to target farms at higher risk of veterinary drug residue contamination for testing programs in combination with incentives, education and training programs to improve mammary health, milk hygiene and safety.

  2. Database dedicated to information published during the Benelux conferences on hormone and veterinary drug residue analyses

    NARCIS (Netherlands)

    Impens, S.; Brabander, H.F. de; Bergwerff, A.A.; Ginkel, L.A. van; Schilt, R.; Stephany, R.W.; Wasch, K. de; Courtheyn, D.; Peteghem, C. van

    2002-01-01

    Every other year scientists working in the field of residue analysis participate the "International Symposium on Hormone and Veterinary Drug Residue Analysis" and "Euroresidue" conferences. In each symposium a lot of innovative information is presented. In order to obtain a retrieval system for this

  3. Residues of veterinary drugs in eggs and their distribution between yolk and white

    NARCIS (Netherlands)

    Kan, C.A.; Petz, M.

    2000-01-01

    Veterinary drugs and feed additives (especially some coccidiostats) can be absorbed by the digestive tract of laying hens and transferred to the egg. Physicochemical characteristics of these compounds determine their pharmacokinetic behavior and distribution to and within the egg. Traditionally the

  4. Investigating the impact of drug crystallinity in amorphous tacrolimus capsules on pharmacokinetics and bioequivalence using discriminatory in vitro dissolution testing and PBPK modeling and simulation.

    Science.gov (United States)

    Purohit, Hitesh S; Trasi, Niraj S; Sun, Dajun D; Chow, Edwin C Y; Wen, Hong; Zhang, Xinyuan; Gao, Yi; Taylor, Lynne S

    2017-12-28

    Delivering a drug in amorphous form in a formulated product is a strategy used to enhance the apparent solubility of a drug substance and its oral bioavailability. Drug crystallization in such products may occur during the manufacturing process or upon storage, reducing the solubility advantage of the amorphous drug. However, the impact of partial drug crystallization in the drug product on the resulting bioavailability and pharmacokinetics is unknown. In this study, dissolution testing of commercial tacrolimus capsules (which are formulated to contain amorphous drug), both fresh and those containing different amounts of crystalline drug, was conducted using both USP and non-compendial dissolution tests with different dissolution media and volumes. A physiologically based pharmacokinetic (PBPK) absorption model was developed to predict the impact of crystallinity extent on the oral absorption of the products and to evaluate the discriminatory ability of the different dissolution methods. Virtual bioequivalence simulations between partially crystallized tacrolimus capsules versus fresh Prograf or generic tacrolimus capsules were performed using the PBPK model and in vitro dissolution data of the various fresh and partially crystallized capsules under USP and non-compendial dissolution conditions. The results suggest that compendial dissolution tests may not be sufficiently discriminatory with respect to the presence of crystallinity in an amorphous formulation. Non-sink dissolution tests using lower dissolution volumes generate more discriminatory profiles that predict different pharmacokinetics of tacrolimus capsules containing different extents of drug crystallinity. In conclusion, the PBPK modeling approach can be used to assess the impact of partial drug crystallinity in the formulated product and to guide the development of appropriate dissolution methods. Copyright © 2017. Published by Elsevier Inc.

  5. Investigation of bioequivalence of a new fixed-dose combination of acarbose and metformin with the corresponding loose combination as well as the drug-drug interaction potential between both drugs in healthy adult male subjects.

    Science.gov (United States)

    Kim, S; Jang, I-J; Shin, D; Shin, D S; Yoon, S; Lim, K S; Yu, K-S; Li, J; Zhang, H; Liu, Y; Brendel, E; Blode, H; Wang, Y

    2014-08-01

    Both metformin and acarbose are recommended monotherapy and add-on therapy in type 2 diabetes mellitus (T2DM). A fixed-dose combination (FDC) of acarbose and metformin has been developed to reduce pill burden and potentially improve compliance. The current study investigated the bioequivalence of the acarbose/metformin FDC compared with the individual agents administered simultaneously (loose combination). Secondary endpoints were the safety and tolerability of the FDC and the potential for drug-drug interactions between acarbose and metformin. A single-centre, randomized, open-label, four-period crossover study was conducted in healthy male Korean subjects aged 18-45 years. Following one-period balanced Williams design, participants were randomized to receive four single oral treatments on different study days separated by ≥7 days' washout. Treatments were as follows: (i) acarbose/metformin 50/500 mg FDC (test); (ii) acarbose 50 mg and metformin 500 mg as loose combination (reference); (iii) acarbose 50 mg; and (iv) metformin 500 mg. Serial blood samples were taken for glucose and insulin levels for 4 h after a sucrose load on the day before and day of study drug administration. Additionally, serial blood samples were taken for analysis of metformin levels for 24 h after each drug containing metformin. The area under the curve for 4 h post-test (AUC0-4 h ) and the maximal serum concentration (Cmax ) of plasma glucose and serum insulin were primary pharmacodynamic (PD) parameters, and Cmax , AUC0-last and AUC for metformin levels were primary pharmacokinetic (PK) parameters. The bioequivalence of the FDC to the loose combination was considered established if the 90% confidence intervals (CIs) of the baseline-adjusted PD parameter ratios (test vs. reference) for plasma glucose and the PK parameter ratios for metformin fell completely within current acceptance limits (0·8-1·25). Thirty-three of 40 randomized subjects completed the study; five withdrew

  6. Xenobiotic-metabolizing enzymes in plants and their role in uptake and biotransformation of veterinary drugs in the environment.

    Science.gov (United States)

    Bártíková, Hana; Skálová, Lenka; Stuchlíková, Lucie; Vokřál, Ivan; Vaněk, Tomáš; Podlipná, Radka

    2015-08-01

    Many various xenobiotics permanently enter plants and represent potential danger for their organism. For that reason, plants have evolved extremely sophisticated detoxification systems including a battery of xenobiotic-metabolizing enzymes. Some of them are similar to those in humans and animals, but there are several plant-specific ones. This review briefly introduces xenobiotic-metabolizing enzymes in plants and summarizes present information about their action toward veterinary drugs. Veterinary drugs are used worldwide to treat diseases and protect animal health. However, veterinary drugs are also unwantedly introduced into environment mostly via animal excrements, they persist in the environment for a long time and may impact on the non-target organisms. Plants are able to uptake, transform the veterinary drugs to non- or less-toxic compounds and store them in the vacuoles and cell walls. This ability may protect not only plant themselves but also other organisms, predominantly invertebrates and wild herbivores. The aim of this review is to emphasize the importance of plants in detoxification of veterinary drugs in the environment. The results of studies, which dealt with transport and biotransformation of veterinary drugs in plants, are summarized and evaluated. In conclusion, the risks and consequences of veterinary drugs in the environment and the possibilities of phytoremediation technologies are considered and future perspectives are outlined.

  7. Drug resistance in nematodes of veterinary importance: a status report.

    Science.gov (United States)

    Kaplan, Ray M

    2004-10-01

    Reports of drug resistance have been made in every livestock host and to every anthelmintic class. In some regions of world, the extremely high prevalence of multi-drug resistance (MDR) in nematodes of sheep and goats threatens the viability of small-ruminant industries. Resistance in nematodes of horses and cattle has not yet reached the levels seen in small ruminants, but evidence suggests that the problems of resistance, including MDR worms, are also increasing in these hosts. There is an urgent need to develop both novel non-chemical approaches for parasite control and molecular assays capable of detecting resistant worms.

  8. Application of PK/PD Modeling in Veterinary Field: Dose Optimization and Drug Resistance Prediction

    Directory of Open Access Journals (Sweden)

    Ijaz Ahmad

    2016-01-01

    Full Text Available Among veterinary drugs, antibiotics are frequently used. The true mean of antibiotic treatment is to administer dose of drug that will have enough high possibility of attaining the preferred curative effect, with adequately low chance of concentration associated toxicity. Rising of antibacterial resistance and lack of novel antibiotic is a global crisis; therefore there is an urgent need to overcome this problem. Inappropriate antibiotic selection, group treatment, and suboptimal dosing are mostly responsible for the mentioned problem. One approach to minimizing the antibacterial resistance is to optimize the dosage regimen. PK/PD model is important realm to be used for that purpose from several years. PK/PD model describes the relationship between drug potency, microorganism exposed to drug, and the effect observed. Proper use of the most modern PK/PD modeling approaches in veterinary medicine can optimize the dosage for patient, which in turn reduce toxicity and reduce the emergence of resistance. The aim of this review is to look at the existing state and application of PK/PD in veterinary medicine based on in vitro, in vivo, healthy, and disease model.

  9. Application of PK/PD Modeling in Veterinary Field: Dose Optimization and Drug Resistance Prediction.

    Science.gov (United States)

    Ahmad, Ijaz; Huang, Lingli; Hao, Haihong; Sanders, Pascal; Yuan, Zonghui

    2016-01-01

    Among veterinary drugs, antibiotics are frequently used. The true mean of antibiotic treatment is to administer dose of drug that will have enough high possibility of attaining the preferred curative effect, with adequately low chance of concentration associated toxicity. Rising of antibacterial resistance and lack of novel antibiotic is a global crisis; therefore there is an urgent need to overcome this problem. Inappropriate antibiotic selection, group treatment, and suboptimal dosing are mostly responsible for the mentioned problem. One approach to minimizing the antibacterial resistance is to optimize the dosage regimen. PK/PD model is important realm to be used for that purpose from several years. PK/PD model describes the relationship between drug potency, microorganism exposed to drug, and the effect observed. Proper use of the most modern PK/PD modeling approaches in veterinary medicine can optimize the dosage for patient, which in turn reduce toxicity and reduce the emergence of resistance. The aim of this review is to look at the existing state and application of PK/PD in veterinary medicine based on in vitro, in vivo, healthy, and disease model.

  10. Stability during cooking of anthelmintic veterinary drug residues in beef

    OpenAIRE

    Cooper, Kevin Mark; Whelan, Michelle; Danaher, Martin; Kennedy, David Glenn

    2011-01-01

    Abstract Anthelmintic drugs are widely used for treatment of parasitic worms in livestock but little is known about the stability of their residues in food under conventional cooking conditions. As part of the European Commission-funded research project ProSafeBeef, cattle were medicated with commercially available anthelmintic preparations, comprising 11 active ingredients (corresponding to 21 marker residues). Incurred meat and liver were cooked by roasting (40 min at 190?C) or...

  11. [The use of pharmacological criteria in the toxicological evaluation of veterinary drugs].

    Science.gov (United States)

    van Leeuwen, F X

    1990-09-01

    The toxicological evaluation of residues of veterinary drugs in foods of animal origin, which is done within the framework of the Netherlands Veterinary Drugs Act, is based on an EEC guide line in which, in addition to the clinical and analytical criteria, the requirements regarding the pharmacological and toxicological evaluation are laid down. In principle, this evaluation is based on classical toxicological criteria. As veterinary drugs have a specific pharmacological action, it is essential that these pharmacological effects should be in included in the toxicological evaluation in view of an adequate protection of public health. The selected starting point is that a pharmacological effect desired in a target animal is regarded as an undesirable effect in consumers. In this presentation, two examples are referred to, viz. the bèta agonist clenbuterol and the bèta-blocking agent carazolol; the approach is compared with a 'classical' toxicological evaluation. This shows that the acceptable daily intake in human individuals (ADI), based on pharmacological criteria is lower by a factor of approximately 50 than is the ADI on the basis of 'classical' toxicological criteria. This clearly illustrates the value of this approach in protecting the health of consumers.

  12. 21 CFR 320.33 - Criteria and evidence to assess actual or potential bioequivalence problems.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Criteria and evidence to assess actual or potential bioequivalence problems. 320.33 Section 320.33 Food and Drugs FOOD AND DRUG ADMINISTRATION... Criteria and evidence to assess actual or potential bioequivalence problems. The Commissioner of Food and...

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

    Directory of Open Access Journals (Sweden)

    Chandan

    2010-10-01

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

  14. 77 FR 66621 - Draft Guidance for Industry on Bioequivalence Recommendation for Lenalidomide Capsules; Availability

    Science.gov (United States)

    2012-11-06

    ... draft guidance, when finalized, will represent the Agency's current thinking on the design of BE studies... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry on Bioequivalence Recommendation... design of bioequivalence (BE) studies to support abbreviated new drug applications (ANDAs) for...

  15. 77 FR 18827 - Draft Guidance for Industry on Bioequivalence Recommendations for Iron Sucrose Injection...

    Science.gov (United States)

    2012-03-28

    ... current thinking on the design of BE studies to support ANDAs for iron sucrose injection. It does not... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry on Bioequivalence... guidance on the design of bioequivalence (BE) studies to support abbreviated new drug applications (ANDAs...

  16. 78 FR 66743 - Draft Guidance for Industry on Bioequivalence Recommendations for Iron Sucrose; Availability

    Science.gov (United States)

    2013-11-06

    ..., will represent the Agency's current thinking on the design of BE studies to support ANDAs for iron... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry on Bioequivalence... on the design of bioequivalence (BE) studies to support abbreviated new drug applications (ANDAs) for...

  17. Antineoplastic drugs in veterinary oncology: excretion in dogs, contamination of the environment and exposure assessment of people at risk

    NARCIS (Netherlands)

    Janssens, T.

    2012-01-01

    Anticancer drugs themselves can cause adverse health effects when administered to human patients. In addition, it has become apparent that personnel in human medicine, occupationally exposed to these anticancer drugs, may also be at risk. The past decades, the use of chemotherapy in veterinary

  18. Target screening of 105 veterinary drug residues in milk using UHPLC/ESI Q-Orbitrap multiplexing data independent acquisition.

    Science.gov (United States)

    Wang, Jian; Leung, Daniel; Chow, Willis; Chang, James; Wong, Jon W

    2018-02-05

    This paper presents a multi-class target screening method for the detection of 105 veterinary drug residues from 11 classes in milk using ultra-high performance liquid chromatography electrospray ionization quadrupole Orbitrap mass spectrometry (UHPLC/ESI Q-Orbitrap). The method is based on a non-target approach of full mass scan and multiplexing data-independent acquisition (Full MS/mDIA). The veterinary drugs include endectocides, fluoroquinolones, ionophores, macrolides, nitroimidazole, NSAIDs, β-lactams, penicillins, phenicols, sulfonamides, and tetracyclines. Veterinary drug residues were extracted from milk using a salting-out and solid-phase extraction (SOSPE) procedure, which entailed the precipitation of milk proteins by an extraction buffer (oxalic acid and EDTA, pH 3) and acetonitrile, a salting-out acetonitrile/water phase separation using ammonium sulfate, and solid-phase extraction for clean-up using polymeric reversed-phase sorbent cartridges. The Q-Orbitrap Full MS/dd-MS2 (data-dependent acquisition) was used to acquire product-ion spectra of individual veterinary drugs to build a compound database and a mass spectral library, whereas its Full MS/mDIA was utilized to acquire sample data from milk for target screening of veterinary drugs fortified at 1.0 or 10.0 μg/kg. The in-spectrum mass correction or solvent background lock-mass correction was used to minimize mass error when building the compound database from experimental dd-MS2 accurate mass data. Retention time alignment and response threshold adjustment were used to eliminate or reduce false negatives and/or false positive rates. The validated method was capable of screening 58% and 96% of 105 veterinary drugs at 1.0 and 10.0 μg/kg, respectively, without manually evaluating every compound during data processing, which will reduce the workload in routine practice.

  19. 76 FR 26307 - Guidance for Industry on the Submission of Summary Bioequivalence Data for Abbreviated New Drug...

    Science.gov (United States)

    2011-05-06

    ... Applications.'' The guidance is intended to assist abbreviated new drug application (ANDA) applicants in... the Federal Register in January 2009 (74 FR 2849, January 16, 2009). The final rule requires ANDA... subjects: Types of ANDA submissions covered by the regulations on BE studies; Recommended format for...

  20. 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 develop...

  1. Organizational aspects of conducting of bioequivalence study

    Directory of Open Access Journals (Sweden)

    Khokhlov A.L.

    2014-03-01

    Full Text Available Aim: to evaluate the organizational aspects of conducting bioequivalence study in Russia on the example of one of the clinical centers, Yaroslavl. Material and methods. On the basis of the Municipal Autonomous institution of health care of the Yaroslavl region Clinical hospital №2 (CH, clinical base of the Department of clinical pharmacology of YSMA was held 93 bioequivalence studies and pharmacokinetics in the period from 2011 to 2014, of which 15 studies of foreign sponsors and 78 of domestic producers. Result.: The studies involved 48 volunteers of both sexes from the database of clinical center CH №2. There were 698 females (48.6% and 739 males (51.4%. The average age of the volunteers was 26,37 years. In each study there were from 18 to 103 volunteers, depending on the design of the research Protocol. At the same time Russian studies ranged about 18-24 volunteers, about 30-103 volunteers abroad. The number of doubles in domestic studies ranged from 2 to 6 persons, and foreign — from 6 to 12 people. 10-15% from the whole number of subjects were not included into the study. Conclusion. In Russia bioequivalence of medicines for more than ten years is the main requirement of medico-biological control generic drugs. Regardless of the manufacturer to the generic drugs are exactly the same as the original drugs, must meet the following requirements: quality efficiency and safety. In connection with the increase in recent years of bioequivalence studies of medicines, require close monitoring of the quality of these studies on the territory of the Russian Federation.

  2. Assessment of veterinary drug retail outlets in two rural areas of ...

    African Journals Online (AJOL)

    Saharan Africa requires significant improvements in animal health with adequate access to veterinary services. Since the 1980s, veterinary services in developing countries including Nigeria has witnessed a decline in government involvement and ...

  3. Generics and cost-effective prescribing in Belgium: does bioequivalence always translate in therapeutic equivalence?

    Science.gov (United States)

    Dupont, A G; Heller, F

    2009-01-01

    As many other countries, Belgium has a policy to promote the use of generic pharmaceutical products. In order to protect consumers, these generic products must be demonstrated to be essentially similar to the previously approved product, typically an innovator product. The therapeutic equivalence of a generic and an innovator product is most commonly based on the demonstration of bioequivalence, i.e. clinically insignificant differences in the rate and extent of drug absorption usually assessed from pharmacokinetic measurements, in a normal and healthy population. This article reviews the bioequivalence requirements for generic products and examines whether bioequivalence always adequately substantiates therapeutic equivalence and interchangeability. Clinical practice has identified a number of drug classes for which generic substitution should be approached with caution. Current bioequivalence requirements are based on a measure of average bioequivalence. There are fears that use of this measure may be inappropriate in the case of a drug with a narrow therapeutic range or high intrasubject or intersubject variability. Under these circumstances, measures of individual and population bioequivalence are proposed to be more accurate than measures of average bioequivalence. Bioequivalence issues are discussed together more general concerns about generic drug substitution, such as differences in product and packaging appearance and differences in excipients.

  4. 77 FR 58399 - Draft Guidance for Industry on Bioequivalence Recommendations for Pentosan Polysulfate Sodium...

    Science.gov (United States)

    2012-09-20

    ... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry on Bioequivalence... recommendations provide specific guidance on the design of bioequivalence (BE) studies to support abbreviated new... regulation (21 CFR 10.115). The draft guidance, when finalized, will represent the Agency's current thinking...

  5. Comparison of veterinary drug residue results in animal tissues by ultrahigh-performance liquid chromatography coupled to triple quadrupole ... use of a commercial lipid removal product

    Science.gov (United States)

    Veterinary drug residues in animal-derived foods must be monitored to ensure food safety, verify proper veterinary practices, enforce legal limits in domestic and imported foods, and other purposes. A common goal in drug residue analysis in foods is to achieve acceptable monitoring results for as m...

  6. Assessment of veterinary drug retail outlets in two rural areas of ...

    African Journals Online (AJOL)

    ADEYEYE

    2017-07-07

    Jul 7, 2017 ... Department of Veterinary Public Health and Preventive Medicine, University of Ilorin, Kwara state,. Nigeria ... Lafiagi rural areas of Kwara state, to asses the owners', sales persons' and business characteristics of veterinary retail outlets with the aid of ... patronise veterinary hospitals. Furthermore, there.

  7. Immunology-Based Techniques for the Detection of Veterinary Drug Residues in Foods

    Science.gov (United States)

    Reig, Milagro; Toldrá, Fidel

    Veterinary drugs are used in farm animals, via the feed or the drinking water, to prevent the outbreak of diseases or even for the treatment of diseases. However, the growth of animals may be promoted through the use of hormones and antibiotics. Depending on the type of residue and the application and washing conditions, these substances or its metabolites may remain in meat and other foods of animal origin and may cause adverse effects on consumers’ health. This is the main reason why its use is strictly regulated or even banned (case of the European Union) in different countries. Antibiotics typically used for growth promotion include chloramphenicol, nitrofurans, and enrofloxacin but others like sulphonamides, macrolides etc. may also be used (Reig & Toldrá, 2007).

  8. Mobility of veterinary drugs in soil with application of manure compost.

    Science.gov (United States)

    Kwon, Jin-Wook

    2011-07-01

    Sulfonamides and tetracyclines are pharmaceuticals widely used to treat human and animal diseases. They are of considerable concern in Korea because of the potential risk of residues in aquatic and terrestrial environments. This study investigated the mobility of veterinary drugs in the soil column with the application of manure compost to assess the risk of groundwater contamination by leaching in the Korean agricultural environment. The degree of sulfonamides and tetracyclines mobility, measured by the concentration of leachates from silty loam soil for 9 days, was observed being on the first day of this study, in the order sulfathiazole, sulfamethazine > sulfamethoxazole > chlortetracycline > oxytetracycline, and the sulfonamides concentrations were about ten times higher than the tetracyclines concentrations with continuous leaching. The results indicate that sulfonamides pose a high risk of ground and surface water contamination and tetracyclines have the potential to persist in soils with bioactive epimers.

  9. Aquatic toxicity of four veterinary drugs commonly applied in fish farming and animal husbandry.

    Science.gov (United States)

    Kołodziejska, Marta; Maszkowska, Joanna; Białk-Bielińska, Anna; Steudte, Stephanie; Kumirska, Jolanta; Stepnowski, Piotr; Stolte, Stefan

    2013-08-01

    Doramectin (DOR), metronidazole (MET), florfenicol (FLO), and oxytetracycline (OXT) are among the most widely used veterinary drugs in animal husbandry or in aquaculture. Contamination of the environment by these pharmaceuticals has given cause for concern in recent years. Even though their toxicity has been thoroughly analyzed, knowledge of their ecotoxicity is still limited. We investigated their aquatic toxicity using tests with marine bacteria (Vibrio fischeri), green algae (Scenedesmus vacuolatus), duckweed (Lemna minor) and crustaceans (Daphnia magna). All the ecotoxicological tests were supported by chemical analyses to confirm the exposure concentrations of the pharmaceuticals used in the toxicity experiments, since deviations from the nominal concentration can result in underestimation of biological effects. It was found that OXT and FLO have a stronger adverse effect on duckweed (EC50=3.26 and 2.96mgL(-1) respectively) and green algae (EC50=40.4 and 18.0mgL(-1)) than on bacteria (EC50=108 and 29.4mgL(-1)) and crustaceans (EC50=114 and 337mgL(-1)), whereas MET did not exhibit any adverse effect in the tested concentration range. For DOR a very low EC50 of 6.37×10(-5)mgL(-1) towards D. magna was determined, which is five orders of magnitude lower than values known for the toxic reference compound K2Cr2O7. Our data show the strong influence of certain veterinary drugs on aquatic organisms and contribute to a sound assessment of the environmental hazards posed by commonly used pharmaceuticals. Copyright © 2013. Published by Elsevier Ltd.

  10. Veterinary drugs and growth promoting agents in animal products : annual report 2012 of the National Reference Laboratory

    NARCIS (Netherlands)

    Stolker, A.A.M.; Sterk, S.S.

    2013-01-01

    This report if the National Reference Laboratory (NRL) for residues of veterinary drugs and growth promoting agents in products of animal origin according to Council Directive 96/23/EC describes the activities employed in 2012. The main tasks of the NRL are communication with Official Laboratories

  11. 75 FR 48928 - Codex Alimentarius Commission: Meeting of the Codex Committee on Residues of Veterinary Drugs in...

    Science.gov (United States)

    2010-08-12

    ....hhs.gov For further information about the public meeting, contact: Ken Lowery, ] International Issues... determination of veterinary drug residues in foods. The Committee is hosted by the United States. Issues To Be... all its programs and activities on the basis of race, color, national origin, gender, religion, age...

  12. Veterinary drugs and growth promoting agents in animal products : annual report 2010 of the National Reference Laboratory

    NARCIS (Netherlands)

    Stolker, A.A.M.; Sterk, S.S.

    2011-01-01

    This report of the National Reference Laboratory (NRL) for residues of veterinary drugs in products of animal origin according to 96/23/EC describes the activities employed in 2010. The main tasks of the NRL are the communication with Routine Field Laboratories (RFL), the preparation of quality

  13. Veterinary drugs and growth promoting agents in animal products : annual report 2011 of the National Reference Laborator

    NARCIS (Netherlands)

    Stolker, A.A.M.; Sterk, S.S.

    2012-01-01

    This report of the National Reference Laboratory (NRL) for residues of veterinary drugs and growth promoting agents in products of animal origin according to Council Directive 96/23/EC describes the activities employed in 2011. The main tasks of the NRL are the communication with Routine Field

  14. 77 FR 16806 - Codex Alimentarius Commission: Meeting of the Codex Committee on Residues of Veterinary Drugs in...

    Science.gov (United States)

    2012-03-22

    ... accessible via the World Wide Web at the following address: http://www.codexalimentarius.org/ . Kevin... Science & Policy, Office of New Animal Drug Evaluation, HFV-100, FDA, Center for Veterinary Medicine, 7520... World Health Organization (WHO). Through adoption of food standards, codes of practice, and other...

  15. [Relative bioavailability and bioequivalence of the antimycotics ketoconazole and fluconazole].

    Science.gov (United States)

    Ptitsina, S N; Bobrov, V I; Borisov, M M

    2006-01-01

    Pharmacokinetics and bioavailability of the antimycotics ketoconazole FPO and fluconazole (Russia) and the analogous drugs nizoral (Belgium) and diflucan (France) were comparatively studied on animals and in clinical trials. The pharmacokinetic parameters of the drugs were determined and their bioequivalence was shown (90-110%) that is evident of their therapeutic equality.

  16. [Simultaneous determination of residual veterinary drugs in livestock products and fish by liquid chromatography with tandem mass spectrometry].

    Science.gov (United States)

    Kajita, Hiroko; Hatakeyama, Eriko

    2008-01-01

    A rapid multiresidue method was developed for determination of 98 veterinary drugs in livestock products and fish by LC/MS/MS. The drugs were extracted with methanol, and the extracted solution was diluted with water. The methanol concentration was adjusted to 50%, and finally the diluted solution was filtered through a microfiltration membrane (0.02 microm diameter pore size) prior to LC/MS/MS. Recoveries of 87 drugs from 4 foods (milk, egg, rainbow trout and cattle muscle) fortified at 0.2 microg/g were in the range of 50-150% with a coefficient of variation (%) of less than 20%. The values obtained by this method from livestock products containing antibiotics were similar to those obtained by the official methods. This proposed method is expected to be useful as a multiresidue analysis method for screening of veterinary drugs in livestock products and fish.

  17. Multiplicity adjustments in testing for bioequivalence.

    Science.gov (United States)

    Hua, Steven Y; Xu, Siyan; D'Agostino, Ralph B

    2015-01-30

    Bioequivalence of two drugs is usually demonstrated by rejecting two one-sided null hypotheses using the two one-sided tests for pharmacokinetic parameters: area under the concentration-time curve (AUC) and maximum concentration (Cmax). By virtue of the intersection-union test, there is no need for multiplicity adjustment in testing the two one-sided null hypotheses within each parameter. However, the decision rule for bioequivalence often requires equivalence to be achieved simultaneously on both parameters that contain four one-sided null hypotheses together; without adjusting for multiplicity, the family wise error rate (FWER) could fail to be controlled at the nominal type-I error rate α. The multiplicity issue for bioequivalence in this regard is scarcely discussed in the literature. To address this issue, we propose two approaches including a closed test procedure that controls FWER for the simultaneous AUC and Cmax bioequivalence and requires no adjustment of the type-I error, and an alpha-adaptive sequential testing (AAST) that controls FWER by pre-specifying the significance level on AUC (α1) and obtaining it for Cmax (α2) adaptively after testing of AUC. While both methods control FWER, the closed test requires testing of eight intersection null hypotheses each at α, and AAST is at times accomplished through a slight deduction in α1 and no deduction in α2 relative to α. The latter considers equivalence reached in AUC a higher importance than that in Cmax. Illustrated with published data, the two approaches, although operate differently, can lead to the same substantive conclusion and are better than a traditional method like Bonferroni adjustment. Copyright © 2014 John Wiley & Sons, Ltd.

  18. A Survey of the Likelihood Approach to Bioequivalence Trials

    Science.gov (United States)

    Choi, Leena; Caffo, Brian; Rohde, Charles

    2009-01-01

    SUMMARY Bioequivalence trials are abbreviated clinical trials whereby a generic drug or new formulation is evaluated to determine if it is “equivalent” to a corresponding previously approved brand-name drug or formulation. In this manuscript, we survey the process of testing bioequivalence and advocate the likelihood paradigm for representing the resulting data as evidence. We emphasize the unique conflicts between hypothesis testing and confidence intervals in this area - which we believe are indicative of the existence of the systemic defects in the frequentist approach - that the likelihood paradigm avoids. We suggest the direct use of profile likelihoods for evaluating bioequivalence. We discuss how the likelihood approach is useful to present the evidence for both average and population bioequivalence within a unified framework. We also examine the main properties of profile likelihoods and estimated likelihoods under simulation. This simulation study shows that profile likelihoods offer a viable alternative to the (unknown) true likelihood for a range of parameters commensurate with bioequivalence research. PMID:18618422

  19. NIGERIAN VETERINARY JOURNAL

    African Journals Online (AJOL)

    ADEYEYE

    Nigerian Veterinary Journal 38(3). 2017. Gberindyer et al. 250. NIGERIAN VETERINARY JOURNAL. ISSN 0331-3026. Nig. Vet. J., September 2017. Vol 38 (3): 250-259. ORIGINAL ARTICLE. Drugs Prescription Pattern in Dogs Diagnosed with Parvovirus Enteritis in Some Veterinary Clinics in Nigeria. Gberindyer, F. A.. 1.

  20. Biomarkers in Veterinary Medicine.

    Science.gov (United States)

    Myers, Michael J; Smith, Emily R; Turfle, Phillip G

    2017-02-08

    This article summarizes the relevant definitions related to biomarkers; reviews the general processes related to biomarker discovery and ultimate acceptance and use; and finally summarizes and reviews, to the extent possible, examples of the types of biomarkers used in animal species within veterinary clinical practice and human and veterinary drug development. We highlight opportunities for collaboration and coordination of research within the veterinary community and leveraging of resources from human medicine to support biomarker discovery and validation efforts for veterinary medicine.

  1. New approach to assess bioequivalence parameters using generalized gamma mixed-effect model (model-based asymptotic bioequivalence test).

    Science.gov (United States)

    Chen, Yuh-Ing; Huang, Chi-Shen

    2014-02-28

    In the pharmacokinetic (PK) study under a 2x2 crossover design that involves both the test and reference drugs, we propose a mixed-effects model for the drug concentration-time profiles obtained from subjects who receive different drugs at different periods. In the proposed model, the drug concentrations repeatedly measured from the same subject at different time points are distributed according to a multivariate generalized gamma distribution, and the drug concentration-time profiles are described by a compartmental PK model with between-subject and within-subject variations. We then suggest a bioequivalence test based on the estimated bioavailability parameters in the proposed mixed-effects model. The results of a Monte Carlo study further show that the proposed model-based bioequivalence test is not only better on maintaining its level but also more powerful for detecting the bioequivalence of the two drugs than the conventional bioequivalence test based on a non-compartmental analysis or the one based on a mixed-effects model with a normal error variable. The application of the proposed model and test is finally illustrated by using data sets in two PK studies. Copyright © 2013 John Wiley & Sons, Ltd.

  2. Bioequivalence evaluation of epinephrine autoinjectors with attention to rapid delivery.

    Science.gov (United States)

    Sclar, David Alexander

    2013-01-01

    Timely and proper injection of epinephrine is critical to prevent serious consequences relating to anaphylaxis. In a recent bioavailability study comparing epinephrine delivery from the Auvi-Q™ and EpiPen(®) epinephrine autoinjectors, the Auvi-Q failed to meet the bioequivalence threshold when using partial area under the curve (AUC) analyses based on zero to Tmax recommended for highly variable drugs such as epinephrine. Peak plasma epinephrine concentrations for the EpiPen occurred 10 minutes (median Tmax) after dosing, while peak concentrations for the Auvi-Q occurred 20 minutes after dosing. Though bioequivalence may be concluded for Cmax, AUCinf, and AUC0-t, for fast-acting therapeutics used to treat life-threatening conditions, such as epinephrine, additional pharmacokinetic parameters such as AUC zero to Tmax may be important to evaluate when assessing bioequivalence.

  3. Screening of veterinary drug residues in milk from individual farms in Macedonia

    Directory of Open Access Journals (Sweden)

    Dimitrieska-Stojkovic Elizabeta

    2011-05-01

    Full Text Available A total of 497 raw milk samples collected at individual farms and collection tanks for milk from eight regions from Macedonia were examined for chloramphenicol, sulfonamides, quinolones and tetracyclines from October 2008 until April 2011. Immunoassay methods were used for the determination of chloramphenicol, sulfonamides and quinolones, and high performance liquid chromatography with Diode Array detection was applied for screening of tetracyclines. The methods were validated according to the recommendations laid down by European Commission Decision 2002/657/EC. The obtained data confirmed that the methods were appropriate for detection of antibiotics determined, at the concentration level of interest. Measured range of concentrations (in μg/kg was 13.5-147.9 for sulfonamides, 0.6-22.0 for quinolones and 17.4-149.1 for tetracyclines, with calculated mean values (in μg/kg 24.7 for sulfonamides, 12.6 for qinolones and 41.9 for tetracyclines. None of the analyzed samples showed presence of chloramphenicol over the minimum required performance level value of the screening method. The calculated estimated daily intakes for the average daily consumption of 200 mL of milk for an adult in Macedonia, for the examined antimicrobials, obtained levels 2 to 100 times lower than the values of the acceptable daily intakes fixed by World Health Organization. This indicates that toxicological risk associated with the consumption of analyzed milk could not be considered as a public health issue with regards to these veterinary drugs.

  4. 78 FR 73200 - Draft Guidance for Industry on Bioequivalence Recommendations for Paliperidone Palmitate Extended...

    Science.gov (United States)

    2013-12-05

    ...). The draft guidance, when finalized, will represent the Agency's current thinking on the design of BE... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry on Bioequivalence... for Paliperidone Palmitate.'' The guidance provides specific recommendations on the design of...

  5. 78 FR 55263 - Draft Guidance for Industry on Bioequivalence Recommendations for Fluticasone Propionate...

    Science.gov (United States)

    2013-09-10

    ....115). The draft guidance, when finalized, will represent the Agency's current thinking on the design... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry on Bioequivalence... Propionate; Salmeterol Xinafoate.'' The recommendations provide specific guidance on the design of...

  6. Bioequivalence study on two brands of 10% enrofloxacin oral ...

    African Journals Online (AJOL)

    A bioequivalence of two brands of 10% enrofloxacin was tested in broiler chickens using a parallel design at 20 mg/kg bodyweight orally. Blood was sampled before and after drug administration for 24 hours. Plasma enrofloxacin concentrations were analyzed using microbiological assay. Peak plasma concentrations ...

  7. Interspecies allometric meta-analysis of the comparative pharmacokinetics of 85 drugs across veterinary and laboratory animal species.

    Science.gov (United States)

    Huang, Q; Gehring, R; Tell, L A; Li, M; Riviere, J E

    2015-06-01

    Allometric scaling is widely used for the determination of first dosage regimen and the interpolation or extrapolation of pharmacokinetic parameters across many animal species during drug development. In this article, 85 drugs used in veterinary medicine obtained from the Food Animal Residue Avoidance Databank database were selected for allometric scaling analysis. Outlier species were identified by statistical methods. The results showed that 77% and 88% of drugs displayed significant correlations between total systemic clearance (CL) and volume of distribution at steady status (Vss) vs. body weight (P allometric exponent b for CL and Vss displays approximate normal distribution, with means (0.87 and 0.99) and standard deviations (0.143 and 0.157) for CL and Vss, respectively. Twelve drugs were identified to have at least one outlier species for CL and ten drugs for Vss. The human CL and Vss were predicted for selected drugs by the obtained allometric equations. The predicted CL and Vss were within a threefold error compared to observed values, except the predicted CL values for antipyrine, warfarin and diazepam. The results can be used to estimate cross-species pharmacokinetic profiles for predicting drug dosages in veterinary species, and to identify those species for which interpolation or extrapolation of pharmacokinetics properties may be problematic. © 2014 John Wiley & Sons Ltd.

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

    Science.gov (United States)

    Reig, Milagro; Toldrá, Fidel

    2008-01-01

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

  9. Analysis of veterinary drugs and metabolites in milk using quadrupole time-of-flight liquid chromatography-mass spectrometry.

    Science.gov (United States)

    Turnipseed, Sherri B; Storey, Joseph M; Clark, Susan B; Miller, Keith E

    2011-07-27

    A quadrupole time-of-flight (Q-TOF) liquid chromatography-mass spectrometry (LC-MS) method was developed to analyze veterinary drug residues in milk. Milk samples were extracted with acetonitrile. A molecular weight cutoff filter was the only cleanup step in the procedure. Initially, a set of target compounds (including representative sulfonamides, tetracyclines, β-lactams, and macrolides) was used for validation. Screening of residues was accomplished by collecting TOF (MS(1)) data and comparing the accurate mass and retention times of found compounds to a database containing information for veterinary drugs. The residues included in the study could be detected in samples fortified at the levels of concern with this procedure 97% of the time. Although the method was intended to be qualitative, an evaluation of the MS data indicated a linear response and acceptable recoveries for a majority of target compounds. In addition, MS/MS data were also generated for the [M + H](+) ions. Product ions for each compound were identified, and their mass accuracy was compared to theoretical values. Finally, incurred milk samples from cows dosed with veterinary drugs, including sulfamethazine, flunixin, cephapirin, or enrofloxacin, were analyzed with Q-TOF LC-MS. In addition to monitoring for the parent residues, several metabolites were detected in these samples by TOF. Proposed identification of these residues could be made by evaluating the MS and MS/MS data. For example, several plausible metabolites of enrofloxacin, some not previously observed in milk, are reported in this study.

  10. 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.

  11. Structural characterization of product ions of regulated veterinary drugs by electrospray ionization and quadrupole time-of-flight mass spectrometry (part 3) Anthelmintics, thyreostats, and flukicides

    Science.gov (United States)

    RATIONALE: Previously we have reported a liquid chromatography tandem mass spectrometry method for the identification and quantification of regulated veterinary drugs. The methods used three selected transition ions but most of these ions lacked structural characterization. The work presented here ...

  12. Characterizing chronic and acute health risks of residues of veterinary drugs in food: latest methodological developments by the joint FAO/WHO expert committee on food additives.

    Science.gov (United States)

    Boobis, Alan; Cerniglia, Carl; Chicoine, Alan; Fattori, Vittorio; Lipp, Markus; Reuss, Rainer; Verger, Philippe; Tritscher, Angelika

    2017-11-01

    The risk assessment of residues of veterinary drugs in food is a field that continues to evolve. The toxicological end-points to be considered are becoming more nuanced and in light of growing concern about the development of antimicrobial resistance, detailed analysis of the antimicrobial activity of the residues of veterinary drugs in food is increasingly incorporated in the assessment. In recent years, the Joint FAO/WHO Expert Committee on Food Additives (JECFA) has refined its approaches to provide a more comprehensive and fit-for-purpose risk assessment. This publication describes in detail the consideration of acute and chronic effects, the estimation of acute and chronic dietary exposure, current approaches for including microbiological endpoints in the risk assessment, and JECFA's considerations for the potential effects of food processing on residues from veterinary drugs. JECFA now applies these approaches in the development of health-based guidance values (i.e. safe exposure levels) for residues of veterinary drugs. JECFA, thus, comprehensively addresses acute and chronic risks by using corresponding estimates for acute and chronic exposure and suitable correction for the limited bioavailability of bound residues by the Gallo-Torres model. On a case-by-case basis, JECFA also considers degradation products that occur from normal food processing of food containing veterinary drug residues. These approaches will continue to be refined to ensure the most scientifically sound basis for the establishment of health-based guidance values for veterinary drug residues.

  13. Residues of veterinary drugs in eggs and possible explanations for their distribution between egg white and yolk

    OpenAIRE

    Kan,Cornelis Adriaan

    2003-01-01

    Veterinary drugs are therapeutically used for laying hens but may also reach them unintentionally via the feed e.g. as a result of cross-contamination during premix manufacture, feed preparation in the feed mill or during feed transport. When these compounds reach the bloodstream, they will occur in the ovary with growing follicles and the oviduct, where the egg white is formed and secreted. The deposition of drugs in either yolk or white or both phases determines where one should look fo...

  14. Bioequivalence of three florfenicol preparations in broilers

    Directory of Open Access Journals (Sweden)

    Husamettin Ekici

    2014-12-01

    Full Text Available This study was aimed to determine the bioequivalence of three different preparations of florfenicol using non-drugged broiler chickens. A total of 28 broiler chickens aging 30-day were divided into four equal groups; these were Group I, II, III, and IV. The birds of Group I (for effective substance were given intravenous (i.v. administration of florfenicol dosed at 40 mg/kg body weight (b.wt.. The birds of Group II (for reference drug, Group III (for test-1 drug, and Group IV (for test-2 drug received florfenicol preparations with water (dosed at 40 mg/kg b.wt. through intracrop administration. Blood samples were collected periodically from the birds of all four groups, and blood plasma was separated. Levels of florfenicol and its metabolite (florfenicol amine in the plasma were measured by High Performance Liquid Chromatography (HPLC. In this study, the limit of detection (LOD for florfenicol and florfenicol amine were recorded as 0.017 and 0.78 µg/mL, respectively. On the other hand, the recovery of florfenicol and florfenicol amine were 83.4-84.6 and 82.2-83.8%, respectively. Based on the values of area under the curve (AUC, maximum concentration (Cmax, and time to maximum concentration (Tmax, test-1 drug was found to be acceptable, whereas test-2 drug was remained below the acceptable limits (80-125% of AUC and Cmax. Thus, it was concluded that test-1 drug was bioequivalent as compared to the reference drug.

  15. Veterinary Drugs and Growth Promoters Residues in Meat and Processed Meats

    Science.gov (United States)

    Reig, Milagro; Toldrá, Fidel

    Veterinary drugs, which comprise a large number of different types of substances, are generally intended for therapeutic (to control infectious diseases) and prophylactic (to prevent against infections) purposes in farm animals. Other substances with growth promoting effect may exert antimicrobial effect against the microbial flora in the gut to take maximum profit of nutrients in the feed or by affecting the animal’s metabolism. Most of these substances are orally active and can be administered either in the feed or in the drinking water. Other active hormones are applied in the form of small implants into the subcutaneous tissue of the ears. These are slow release (several weeks or months) devices and the ears are discarded at the slaughter. Growth promoters allow a better efficiency in the feed conversion rate. The net effect is an increased protein deposition, partly due to muscle proteases inhibition (Fiems, Buts, Boucque, Demeyer, & Cottyn, 1990), usually linked to fat utilization (Brockman & Laarveld, 1986). The result is a leaner meat (Lone, 1997) with some toughness derived from the production of connective tissue and collagen crosslinking (Miller, Judge, Diekman, Hudgens, & Aberle, 1989; Miller, Judge, & Schanbacher, 1990). Some recent fraudulent practices, consisting of the use of a kind of “cocktails” or mixtures of several substances like β-agonists and corticosteroids at very low amounts (Monsón et al., 2007), are difficult to detect with modern analytical instrumentation. They try to obtain a synergistic effect for a similar growth promotion with lower probability of detection by official control laboratories (Reig & Toldrá, 2007).

  16. Bioequivalence of ciprofloxacin tablet formulations assessed in Indonesian volunteers.

    Science.gov (United States)

    Harahap, Y; Prasaja, B; Indriati, E; Lusthom, W; Lipin

    2007-06-01

    Determination of the bioequivalence of two ciprofloxacin tablet formulations (test formulation manufactured by Novell Pharmaceutical Laboratories, Indonesia, reference formulation from Quimica Farmaceutica Bayer, Spain). 24 healthy volunteers received each of the two ciprofloxacin formulations at a dose of 500 mg in a 2-way crossover design. Blood samples were obtained prior to dosing and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and24h after drug administration. Plasma concentrations of ciprofloxacin were monitored using high-performance liquid chromatography over a period of 24 h after administration. The pharmacokinetics parameter AUC0-24h, AUC0-infinity and Cmax were tested for bioequivalence after log-transformation of data and ratios of tmax were evaluated non-parametrically. The point estimates and 90% confidence intervals for AUC0-24h, AUC0-infinity and Cmax were 97.55% (92.71 - 102.6%), 97.63% (92.90 - 102.59%) and 95.84% (89.95 - 102.10%), respectively, satisfying the bioequivalence criteria of the European Committee for Proprietary Medicinal Products and the US Food and Drug Administration guidelines. These results indicate that two medications of ciprofloxacin are bioequivalent and, thus, may be prescribed interchangeably.

  17. Workshop report: the 2012 antimicrobial agents in veterinary medicine: exploring the consequences of antimicrobial drug use: a 3-D approach.

    Science.gov (United States)

    Martinez, M; Blondeau, J; Cerniglia, C E; Fink-Gremmels, J; Guenther, S; Hunter, R P; Li, X-Z; Papich, M; Silley, P; Soback, S; Toutain, P-L; Zhang, Q

    2014-02-01

    Antimicrobial resistance is a global challenge that impacts both human and veterinary health care. The resilience of microbes is reflected in their ability to adapt and survive in spite of our best efforts to constrain their infectious capabilities. As science advances, many of the mechanisms for microbial survival and resistance element transfer have been identified. During the 2012 meeting of Antimicrobial Agents in Veterinary Medicine (AAVM), experts provided insights on such issues as use vs. resistance, the available tools for supporting appropriate drug use, the importance of meeting the therapeutic needs within the domestic animal health care, and the requirements associated with food safety and food security. This report aims to provide a summary of the presentations and discussions occurring during the 2012 AAVM with the goal of stimulating future discussions and enhancing the opportunity to establish creative and sustainable solutions that will guarantee the availability of an effective therapeutic arsenal for veterinary species. © Published (2014). This article is a U.S. Government work and is in the public domain in the USA.

  18. Determination of pesticides and veterinary drug residues in food by liquid chromatography-mass spectrometry: A review

    Energy Technology Data Exchange (ETDEWEB)

    Masiá, Ana [Food and Environmental Safety Research Group, Department of Preventive Medicine and Public Health, Food Science, Toxicology and Legal Medicine, University of Valencia, Valencia (Spain); Research Center on Desertification (CIDE, UV-CSIC-GV), Carretera Moncada-Náquera, Moncada (Spain); Suarez-Varela, Maria Morales; Llopis-Gonzalez, Agustin [Unit of Public Health, Hygiene and Environmental Health, Department of Preventive Medicine and Public Health, Food Science, Toxicology and Legal Medicine, University of Valencia, Valencia (Spain); CIBER Epidemiología y Salud Pública (CIBERESP), Madrid (Spain); Center for Advanced Research in Public Health (CSISP-FISABIO), Valencia (Spain); Picó, Yolanda, E-mail: Yolanda.Pico@uv.es [Food and Environmental Safety Research Group, Department of Preventive Medicine and Public Health, Food Science, Toxicology and Legal Medicine, University of Valencia, Valencia (Spain); Research Center on Desertification (CIDE, UV-CSIC-GV), Carretera Moncada-Náquera, Moncada (Spain); CIBER Epidemiología y Salud Pública (CIBERESP), Madrid (Spain)

    2016-09-14

    Monitoring of pesticides and veterinary drug residues is required to enforce legislation and guarantee food safety. Liquid chromatography-mass spectrometry (LC-MS) is the prevailing technique for assessing both types of residues because LC offers a versatile and universal separation mechanism suitable for non-gas chromatography (GC) amenable and the majority of GC-amenable compounds. This characteristic becomes more relevant when LC is coupled to MS because the high sensitivity and specificity of the detector allows to apply generic sample preparation procedures, which simultaneously extract a wide variety of residues with different physico-chemical properties. Determination of metabolites and degradation products, non-target suspected screening of an increasing number of residues, and even unknowns identification are also becoming inherent LC-MS advantages thanks to the latest advances. For routine analysis and, in particular, for official surveillance purposes in food control, analytical methods properly validated following strict guidelines are needed. After a brief introduction and an outline of the legislation applicable around the world, aspects such as improvement of specificity of high-throughput methods, resolution and mass accuracy of identification strategies and quantitative accuracy are critically reviewed in this article. In them, extraction, separation and determination are emphasized. The main objective is to offer an assessment of the state of the art and identify research needs and future trends in determining pesticide and veterinary drug residues in food by LC-MS. - Highlights: • An overview of status and future trends in this field. • Analytical method's compliance with guidelines to ensure reliability. • QuEChERS platform is a referent to extract both, pesticides and veterinary drugs in food. • The progress that liquid chromatography has shown in recent years is revised. • Determination of target, non-target and unknowns is

  19. Quantitative analysis of veterinary drugs in bovine muscle and milk by liquid chromatography quadrupole time-of-flight mass spectrometry.

    Science.gov (United States)

    Saito-Shida, Shizuka; Sakai, Takatoshi; Nemoto, Satoru; Akiyama, Hiroshi

    2017-07-01

    A simple and reliable multiresidue method for quantitative determination of veterinary drugs in bovine muscle and milk using liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) was developed. Critical MS parameters such as capillary voltage, cone voltage, collision energy, desolvation gas temperature and extraction mass window were carefully optimised to obtain the best possible sensitivity. Analytical samples were prepared using extraction with acetonitrile and hexane in the presence of anhydrous sodium sulphate and acetic acid, followed by ODS cartridge clean-up. The developed method was validated for 82 veterinary drugs in bovine muscle and milk at spike levels of 0.01 and 0.1 mg kg(-)(1). With the exception of cefoperazone and phenoxymethylpenicillin, all these compounds exhibited sufficient signal intensity at 0.01 μg ml(-1) (equivalent to 0.01 mg kg(-)(1)), indicating the high sensitivity of the developed method. For most targets, the determined accuracies were within 70-120%, with repeatability and reproducibility being below 20% at both levels. Except for sulfathiazole in bovine muscle, no interfering peaks at target compound retention times were detected in the blank extract, indicating that the developed method is highly selective. The absence of sulfathiazole in bovine muscle was confirmed by simultaneous acquisition at low and high collision energies to afford exact masses of molecular adduct and fragment ions. Satisfactory linearity was observed for all compounds, with matrix effects being negligible for most targets in bovine muscle and milk at both spike levels. Overall, the results suggest that the developed LC-QTOF-MS method is suitable for routine regulatory-purpose analysis of veterinary drugs in bovine muscle and milk.

  20. Generic lamotrigine versus brand-name Lamictal bioequivalence in patients with epilepsy: A field test of the FDA bioequivalence standard.

    Science.gov (United States)

    Ting, Tricia Y; Jiang, Wenlei; Lionberger, Robert; Wong, Jessica; Jones, Jace W; Kane, Maureen A; Krumholz, Allan; Temple, Robert; Polli, James E

    2015-09-01

    To test the current U.S. Food and Drug Administration (FDA) bioequivalence standard in a comparison of generic and brand-name drug pharmacokinetic (PK) performance in "generic-brittle" patients with epilepsy under clinical use conditions. This randomized, double-blind, multiple-dose, steady-state, fully replicated bioequivalence study compared generic lamotrigine to brand-name Lamictal in "generic-brittle" patients with epilepsy (n = 34) who were already taking lamotrigine. Patients were repeatedly switched between masked Lamictal and generic lamotrigine. Intensive PK blood sampling at the end of each 2-week treatment period yielded two 12-h PK profiles for brand-name and generic forms for each patient. Steady-state area under the curve (AUC), peak plasma concentration (Cmax ), and minimum plasma concentration (Cmin ) data were subjected to conventional average bioequivalence (ABE) analysis, reference-scaled ABE analysis, and within-subject variability (WSV) comparisons. In addition, generic-versus-brand comparisons in individual patients were performed. Secondary clinical outcomes included seizure frequency and adverse events. Generic demonstrated bioequivalence to brand. The 90% confidence intervals of the mean for steady-state AUC, Cmax , and Cmin for generic-versus-brand were 97.2-101.6%, 98.8-104.5%, and 93.4-101.0%, respectively. The WSV of generic and brand were also similar. Individual patient PK ratios for generic-versus-brand were similar but not identical, in part because brand-versus-brand profiles were not identical, even though subjects were rechallenged with the same product. Few subjects had seizure exacerbations or tolerability issues with product switching. One subject, however, reported 267 focal motor seizures, primarily on generic, although his brand and generic PK profiles were practically identical. Some neurologists question whether bioequivalence in healthy volunteers ensures therapeutic equivalence of brand and generic antiepileptic drugs

  1. Sample-based reporting of official national control of veterinary drug residues

    DEFF Research Database (Denmark)

    Andersen, Jens Hinge; Jensen, Louise Grønhøj Hørbye; Madsen, Helle L.

    Data collection is an essential prerequisite for assessing compliance of chemical residues in food and for risk assessment. The present system for collecting aggregated data of residues of veterinary medicinal products and other substances in animals and animal products has limitations for risk...

  2. [Development of the databases for ADI (acceptable daily intake) and relevant information on food additives, pesticides and veterinary drugs].

    Science.gov (United States)

    Sugita, Takiko; Sasaki, Shiho; Tanaka, Keiko; Toda, Miou; Uneyama, Chikako; Yamamoto, Miyako; Morikawa, Kaoru

    2006-01-01

    Databases for ADI (Acceptable Daily Intake) and relevant information on food additives, pesticides and veterinary drugs were developed. The databases we developed are easily accessible on the web, and contain ADIs, latest evaluation year, classification and use, as well as synonym and CAS registry number. The databases are designed to be easily updated by researchers as ADI and relevant information are updated or added without delay. The database for food additives has already provided from the homepage of NIHS, and the access log of the web site was 1325/month in December 2005 and 2179/month in March 2006.

  3. Model-based analyses of bioequivalence crossover trials using the stochastic approximation expectation maximisation algorithm.

    Science.gov (United States)

    Dubois, Anne; Lavielle, Marc; Gsteiger, Sandro; Pigeolet, Etienne; Mentré, France

    2011-09-20

    In this work, we develop a bioequivalence analysis using nonlinear mixed effects models (NLMEM) that mimics the standard noncompartmental analysis (NCA). We estimate NLMEM parameters, including between-subject and within-subject variability and treatment, period and sequence effects. We explain how to perform a Wald test on a secondary parameter, and we propose an extension of the likelihood ratio test for bioequivalence. We compare these NLMEM-based bioequivalence tests with standard NCA-based tests. We evaluate by simulation the NCA and NLMEM estimates and the type I error of the bioequivalence tests. For NLMEM, we use the stochastic approximation expectation maximisation (SAEM) algorithm implemented in monolix. We simulate crossover trials under H(0) using different numbers of subjects and of samples per subject. We simulate with different settings for between-subject and within-subject variability and for the residual error variance. The simulation study illustrates the accuracy of NLMEM-based geometric means estimated with the SAEM algorithm, whereas the NCA estimates are biased for sparse design. NCA-based bioequivalence tests show good type I error except for high variability. For a rich design, type I errors of NLMEM-based bioequivalence tests (Wald test and likelihood ratio test) do not differ from the nominal level of 5%. Type I errors are inflated for sparse design. We apply the bioequivalence Wald test based on NCA and NLMEM estimates to a three-way crossover trial, showing that Omnitrope®; (Sandoz GmbH, Kundl, Austria) powder and solution are bioequivalent to Genotropin®; (Pfizer Pharma GmbH, Karlsruhe, Germany). NLMEM-based bioequivalence tests are an alternative to standard NCA-based tests. However, caution is needed for small sample size and highly variable drug. Copyright © 2011 John Wiley & Sons, Ltd.

  4. Considerations on the aquaculture development and on the use of veterinary drugs: special issue for fluoroquinolones--a review.

    Science.gov (United States)

    Quesada, Silvia Pilco; Paschoal, Jonas Augusto Rizzato; Reyes, Felix Guillermo Reyes

    2013-09-01

    Aquaculture has become an important source of fish available for human consumption. In order to achieve greater productivity, intensive fish cultivation systems are employed, which can cause greater susceptibility to diseases caused by viruses, bacteria, fungi, and parasites. Antimicrobial substances are compounds used in livestock production with the objectives of inhibiting the growth of microorganisms and treatment or prevention of diseases. It is well recognized that the issues of antimicrobial use in food animals are of global concern about its impact on food safety. This paper present an overview of the aquaculture production in the whole world, raising the particularities in Brazil, highlighting the importance of the use of veterinary drugs in this system of animal food production, and address the potential risks arising from their indiscriminate use and their impacts on aquaculture production as they affect human health and the environment. The manuscript also discusses the analytical methods commonly used in the determination of veterinary drug residues in fish, with special issue for fluroquinolones residues and with emphasis on employment of LC-MS/MS analytical technique. © 2013 Institute of Food Technologists®

  5. Desorption electrospray ionization-high resolution mass spectrometry for the screening of veterinary drugs in cross-contaminated feedstuffs.

    Science.gov (United States)

    Seró, Raquel; Núñez, Oscar; Bosch, Jaume; Grases, José M; Rodríguez, Pilar; Moyano, Encarnacion; Galceran, Martia Teresa

    2015-09-01

    In this study, a desorption electrospray ionization-high resolution mass spectrometry (DESI-HRMS) screening method was developed for fast identification of veterinary drugs in cross-contaminated feedstuffs. The reliable detection was performed working at high resolution (70,000 full width half maximum, FWHM) using an orbitrap mass analyzer. Among the optimized DESI parameters, the solvent (acetonitrile/water, 80:20, v/v) and the sample substrate (poly-tetrafluoroethylene, PTFE) were critical to obtain the best sensitivity. To analyze the solid feed samples, different approaches were tested and a simple solid-liquid extraction and the direct analysis of an aliquot (2 μL) of the extract after letting it dry on the PTFE printed spot provided the best results. The identification of the veterinary drugs (target and non-target) in the cross-contaminated feedstuffs based on the accurate mass measurement and the isotopic pattern fit was performed automatically using a custom-made database. The positive cross-contaminated feed samples were quantified by ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The results obtained demonstrate that DESI-HRMS can be proposed as a fast and suitable screening method to identify positive cross-contaminated feedstuffs reducing the number of samples to be subsequently quantified by UHPLC-MS/MS, thus improving the productivity in quality control laboratories.

  6. Open questions on bioequivalence: some problems and some solutions.

    Science.gov (United States)

    Marzo, A

    1999-10-01

    This paper focuses on some specific situations where bioequivalence requires careful attention and tailored protocols in order to overcome intrinsic difficulties either marginally covered or fully neglected by operating guidelines. Some problems congregate with serious difficulties, namely high variability, very poorly absorbed drugs and endogenous substances with their own baseline. With endogenous substances, the dilemma faced is whether to subtract baseline from post-dose values in assessing bioequivalence. Either approach has intrinsic problems and is somewhat puzzling. In an attempt to resolve other existing problems, the most appropriate approach should be selected on a case-by-case basis, ensuring that the adopted procedure does not conflict with operating guidelines and scientific literature on the matter. Problematic cases include the management of trials with a predominant active metabolite, the absence of a reliable analytical bioassay, the availability of various strengths of the same drug on the market, a wide acceptability titre range, the management of studies on topical drugs that are devoid of systemic activity, the management of drugs that cannot be given for ethical reasons to healthy subjects or that may cause adverse events, especially when a steady state design is required. The parallel group study design appears to be more appropriate than the cross-over or the individual bioequivalence design in assessing drugs with a long half-life. Some pharmacokinetic and statistical analysis-related issues are also discussed such as the sequence/period interaction sometimes encountered in these trials, which, in the absence of the carry-over effect, does not bias the bioequivalence results and the need to process data with non-compartmental pharmacokinetic analysis. Copyright 1999 Academic Press.

  7. Veterinary drug usage and antimicrobial resistance in bacteria of animal origin

    DEFF Research Database (Denmark)

    Aarestrup, Frank Møller

    2005-01-01

    In the production of food animals, large amounts of antimicrobial agents are used for therapy and prophylaxis of bacterial infections and in feed to promote growth. There are large variations in the amounts of antimicrobial agents used to produce the same amount of meat among the different Europe...... monitoring the occurrence and development of resistance and consumption of antimicrobial agents are strongly desirable, as is research into the most appropriate ways to use antimicrobial agents in veterinary medicine....

  8. "Assessment of different bioequivalent metrics in Rifampin bioequivalence study "

    Directory of Open Access Journals (Sweden)

    "Rouini MR

    2002-08-01

    Full Text Available The use of secondary metrics has become special interest in bioequivalency studies. The applicability of partial area method, truncated AUC and Cmax/AUC has been argued by many authors. This study aims to evaluate the possible superiority of these metrics to primary metrics (i.e. AUCinf, Cmax and Tmax. The suitability of truncated AUC for assessment of absorption extent as well as Cmax/AUC and partial AUC for the evaluation of absorption rate in bioequivalency determination was investigated following administration of same product as test and reference to 7 healthy volunteers. Among the pharmacokinetic parameters obtained, Cmax/AUCinf was a better indicator or absorption rate and the AUCinf was more sensitive than truncated AUC in evaluation of absorption extent.

  9. 78 FR 69991 - Advisory Committee; Veterinary Medicine Advisory Committee; Termination

    Science.gov (United States)

    2013-11-22

    ... HUMAN SERVICES Food and Drug Administration 21 CFR Part 14 Advisory Committee; Veterinary Medicine... Food and Drug Administration (FDA) is announcing the termination of the Veterinary Medicine Advisory... [email protected] . SUPPLEMENTARY INFORMATION: The Veterinary Medicine Committee was...

  10. 75 FR 52605 - Veterinary Medicine Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2010-08-26

    ... HUMAN SERVICES Food and Drug Administration Veterinary Medicine Advisory Committee; Notice of Meeting... the public. Name of Committee: Veterinary Medicine Advisory Committee. General Function of the...-1100. Contact Person: Aleta Sindelar, Center for Veterinary Medicine (HFV-3), Food and Drug...

  11. Targeted Multiresidue Analysis of Veterinary Drugs in Milk-Based Powders Using Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS).

    Science.gov (United States)

    Wittenberg, James B; Simon, Kelli A; Wong, Jon W

    2017-08-30

    An analytical method was developed and validated for the determination of 40 veterinary drugs in various milk-based powders. The method involves acetonitrile/water extraction, solid-phase filtration for lipid removal in fat-containing matrices, and analysis using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The limits of quantitation (LOQ) ranged from 0.02 to 82 ng/g. Acceptable recoveries (70-120%, RSD powder. Similar results were obtained for whole milk powder, milk protein concentrate, whey protein concentrate, and whey protein isolate. This new method will allow for better monitoring of a wide range of veterinary drugs in milk-based powders.

  12. Effectiveness of action in India to reduce exposure of Gyps vultures to the toxic veterinary drug diclofenac.

    Directory of Open Access Journals (Sweden)

    Richard Cuthbert

    Full Text Available Contamination of their carrion food supply with the non-steroidal anti-inflammatory drug diclofenac has caused rapid population declines across the Indian subcontinent of three species of Gyps vultures endemic to South Asia. The governments of India, Pakistan and Nepal took action in 2006 to prevent the veterinary use of diclofenac on domesticated livestock, the route by which contamination occurs. We analyse data from three surveys of the prevalence and concentration of diclofenac residues in carcasses of domesticated ungulates in India, carried out before and after the implementation of a ban on veterinary use. There was little change in the prevalence and concentration of diclofenac between a survey before the ban and one conducted soon after its implementation, with the percentage of carcasses containing diclofenac in these surveys estimated at 10.8 and 10.7%, respectively. However, both the prevalence and concentration of diclofenac had fallen markedly 7-31 months after the implementation of the ban, with the true prevalence in this third survey estimated at 6.5%. Modelling of the impact of this reduction in diclofenac on the expected rate of decline of the oriental white-backed vulture (Gyps bengalensis in India indicates that the decline rate has decreased to 40% of the rate before the ban, but is still likely to be rapid (about 18% year(-1. Hence, further efforts to remove diclofenac from vulture food are still needed if the future recovery or successful reintroduction of vultures is to be feasible.

  13. Multiresidue Screening of Veterinary Drugs in Meat, Milk, Egg, and Fish Using Liquid Chromatography Coupled with Ion Trap Time-of-Flight Mass Spectrometry.

    Science.gov (United States)

    Kang, JeongWoo; Park, Su-Jeong; Park, Hae-Chul; Hossain, Md Akil; Kim, Myeong-Ae; Son, Seong-Wan; Lim, Chae-Mi; Kim, Tae-Wan; Cho, Byung-Hoon

    2017-06-01

    New approaches to veterinary drug screening based on liquid chromatography-mass spectrometry (LC-MS/MS) and time-of-flight mass spectrometry (ToF/MS) are rapid and have high selectivity and sensitivity. In this study, we developed a multiresidue method for screening over 100 veterinary drug residues using ion trap (IT)-ToF/MS. The screened compounds comprised major drug classes used in veterinary practice, representing the following: amphenicols, anthelmintics, benzimidazoles, β-lactams, coccidiostats, ionophores, macrolides, non-steroidal anti-inflammatory drugs, quinolones, sulfonamides, tetracyclines, and tranquilizers. The method was developed based on chromatographic retention time, specific accurate mass, isotope distribution, and fragment data. Each compound was validated at three levels, and the mass accuracy, accuracy, and repeatability were calculated. All parameters showed acceptable values and conformed to the Commission Decision 2002/657/EC criteria. This screening method can simultaneously analyze over 100 veterinary drugs in meat, milk, eggs, and fish in a single analytical run.

  14. Identification of transformation products of pesticides and veterinary drugs in food and related matrices: use of retrospective analysis.

    Science.gov (United States)

    Gómez-Pérez, María Luz; Romero-González, Roberto; Vidal, José Luis Martínez; Frenich, Antonia Garrido

    2015-04-10

    Retrospective analysis has been applied in different samples, including honey, meat, feed and nutraceutical products from ginkgo biloba, soya, royal jelly and green tea, with the aim of searching transformation products of pesticides and veterinary drugs, which were not included in an initial analysis. Generic extraction and analytical procedures based on high resolution mass spectrometry (Exactive-Orbitrap analyser was used) have been applied. All obtained data have been reprocessed and some compounds as anhydroerythromycin in honey and 3,5,6-trichloro-2-pyridinol in feed have been detected, demonstrating the applicability and the utility of the procedure. Advantages and disadvantages of retrospective approach have been highlighted. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. 75 FR 15387 - Veterinary Feed Directive

    Science.gov (United States)

    2010-03-29

    ... HUMAN SERVICES Food and Drug Administration 21 CFR Parts 510, 514, and 558 Veterinary Feed Directive... relating to veterinary feed directive (VFD) drugs. FDA's VFD regulation, which became effective on January... CONTACT: Neal Bataller, Center for Veterinary Medicine (HFV-230), Food and Drug Administration, 7500...

  16. Development of starch based mucoadhesive vaginal drug delivery systems for application in veterinary medicine.

    Science.gov (United States)

    Gök, Mehmet Koray; Özgümüş, Saadet; Demir, Kamber; Cirit, Ümüt; Pabuccuoğlu, Serhat; Cevher, Erdal; Özsoy, Yıldız; Bacınoğlu, Süleyman

    2016-01-20

    The aim of this study was to prepare and evaluate the mucoadhesive, biocompatible and biodegradable progesterone containing vaginal tablets based on modified starch copolymers for the estrus synchronization of ewes. Starch-graft-poly(acrylic acid) copolymers (S-g-PAA) were synthesized and characterized. The vaginal tablets were fabricated with S-g-PAA and their equilibrium swelling degree (Qe) and matrix erosion (ME%) were determined in lactate buffer solution. In vitro, mucoadhesive properties of the tablets were investigated by using ewe vaginal mucosa and in vivo residence time were also investigated. In vitro and in vivo progesterone release profiles from the tablets were compared with two commercial products. Tablet formulation containing wheat starch based grafted copolymer (WS-g-PAA)gc indicated promising results and might be convenient as an alternative product to the commercial products in veterinary medicine. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Bioequivalence of two lansoprazole delayed release capsules 30 mg in healthy male volunteers under fasting, fed and fasting-applesauce conditions: a partial replicate crossover study design to estimate the pharmacokinetics of highly variable drugs.

    Science.gov (United States)

    Thota, S; Khan, S M; Tippabhotla, S K; Battula, R; Gadiko, C; Vobalaboina, V

    2013-11-01

    An open-label, 2-treatment, 3-sequence, 3-period, single-dose, partial replicate crossover studies under fasting (n=48), fed (n=60) and fasting-applesauce (n=48) (sprinkled on one table spoonful of applesauce) modalities were conducted in healthy adult male volunteers to evaluate bioequivalence between 2 formulations of lansoprazole delayed release capsules 30 mg. In all the 3 studies, as per randomization, either test or reference formulations were administered in a crossover manner with a required washout period of at least 7 days. Blood samples were collected adequately (0-24 h) to determine lansoprazole plasma concentrations using a validated LC-MS/MS analytical method. To characterize the pharmacokinetic parameters (Cmax, AUC0-t, AUC0-∞, Tmax, Kel and T1/2) of lansoprazole, non-compartmental analysis and ANOVA was applied on ln-transformed values. The bioequivalence was tested based on within-subject variability of the reference formulation. In fasting and fed studies (within-subject variability>30%) bioequivalence was evaluated with scaled average bioequivalence, hence for the pharmacokinetic parameters Cmax, AUC0-t and AUC0-∞, the 95% upper confidence bound for (μT-μR)2-θσ2 WR was ≤0, and the point estimates (test-to-reference ratio) were within the regulatory acceptance limit 80.00-125.00%. In fasting-applesauce study (within-subject variabilitybioequivalence was evaluated with average bioequivalence, the 90% CI of ln-transformed data of Cmax, AUC0-t and AUC0-∞ were within the regulatory acceptance limit 80.00-125.00%. Based on these aforesaid statistical inferences, it was concluded that the test formulation is bioequivalent to reference formulation. © Georg Thieme Verlag KG Stuttgart · New York.

  18. 78 FR 52777 - Draft Guidance for Industry on Bioequivalence Recommendations for Risperidone Injection...

    Science.gov (United States)

    2013-08-26

    ... on Bioequivalence Recommendations for Risperidone Injection; Availability AGENCY: Food and Drug... availability of a revised draft guidance for industry entitled ``Draft Guidance on Risperidone.'' The guidance... drug applications (ANDAs) for risperidone injection. DATES: Although you can comment on any guidance at...

  19. The veterinary drug ivermectin influences immune response in the yellow dung fly (Scathophaga stercoraria)

    Energy Technology Data Exchange (ETDEWEB)

    West, Helen M. [Division of Agricultural and Environmental Sciences, School of Biosciences, University of Nottingham, University Park, Nottingham, NG7 2RD (United Kingdom)], E-mail: helen.west@nottingham.ac.uk; Tracy, Saoirse R. [Division of Agricultural and Environmental Sciences, School of Biosciences, University of Nottingham, University Park, Nottingham, NG7 2RD (United Kingdom)

    2009-03-15

    Phenoloxidase (PO) is a key enzyme involved in the immune response of insects. We show that egg-to-adult exposure to residues of 0.001, but not 0.0005 mg kg{sup -1} ivermectin elevated PO activity in yellow dung flies (Scathophaga stercoraria) developing in cattle dung. Fly fat content was unaffected by the treatments. Therefore, the response of PO was a direct effect of ivermectin and not an indirect one caused by an alteration in body 'condition'. This supports the non-intuitive conclusion that flies surviving exposure to faecal residues may have enhanced immune function. To our knowledge, this is the first study to assess the effects on PO activity of insecticidal residues in livestock dung. The non-target effects of such residues are of wide interest, given the global use of veterinary products. - Phenoloxidase activity in Scathophaga stercoraria is enhanced by ivermectin and that effect is transferred to the adult fly from the larval stage.

  20. Bioequivalence evaluation of epinephrine autoinjectors with attention to rapid delivery

    Directory of Open Access Journals (Sweden)

    Sclar DA

    2013-04-01

    Full Text Available David Alexander Sclar Department of Pharmacy Practice, College of Pharmacy, Midwestern University, Glendale, AZ, USA Abstract: Timely and proper injection of epinephrine is critical to prevent serious consequences relating to anaphylaxis. In a recent bioavailability study comparing epinephrine delivery from the Auvi-Q™ and EpiPen® epinephrine autoinjectors, the Auvi-Q failed to meet the bioequivalence threshold when using partial area under the curve (AUC analyses based on zero to Tmax recommended for highly variable drugs such as epinephrine. Peak plasma epinephrine concentrations for the EpiPen occurred 10 minutes (median Tmax after dosing, while peak concentrations for the Auvi-Q occurred 20 minutes after dosing. Though bioequivalence may be concluded for Cmax, AUCinf, and AUC0–t, for fast-acting therapeutics used to treat life-threatening conditions, such as epinephrine, additional pharmacokinetic parameters such as AUC zero to Tmax may be important to evaluate when assessing bioequivalence. Keywords: anaphylaxis, therapy, pharmacokinetics, bioavailability, EpiPen, Tmax

  1. The importance of bioequivalence study: focus on clopidogrel

    Directory of Open Access Journals (Sweden)

    Arini Setiawati

    2011-05-01

    Full Text Available Bioequivalence (BE study is required to show whether a generic copy product can be interchangeable with the brand innovator product. The aim of this article is to provide the rationale for conducting BE studies, the main products requiring BE studies, the design and conduct of BE studies in general, with focus on clopidogrel. All of the clopidogrel generic products in Indonesia have been shown to be BE to the innovator product Plavix® and they contain API (active pharmaceutical ingredient clopidogrel form 1 that complies with USP 30, 1997 requirements: the R-enantiomer content is not more than 1%. A proof that bioequivalence (BE means therapeutic equivalence (TE is also provided for cardiovascular drugs. Clopidogrel has 2 polymorphic forms, form 1 and form 2, which have the same indications. At least one pivotal study of clopidogrel, CAPRIE, used clopidogrel form 1. An atherothrombotic event may be associated with clopidogrel resistance, which occur in about 4 to 30% of patients treated with conventional doses of clopidogrel. (Med J Indones 2011; 20:149-53Keywords: bioequivalent, clopidogrel

  2. Ion-exchange solid-phase extraction combined with liquid chromatography-tandem mass spectrometry for the determination of veterinary drugs in organic fertilizers.

    Science.gov (United States)

    Zhao, Zhiyong; Zhang, Yanmei; Xuan, Yanfang; Song, Wei; Si, Wenshuai; Zhao, Zhihui; Rao, Qinxiong

    2016-06-01

    The analysis of veterinary drugs in organic fertilizers is crucial for an assessment of potential risks to soil microbial communities and human health. We develop a robust and sensitive method to quantitatively determine 19 veterinary drugs (amantadine, sulfonamides and fluoroquinolones) in organic fertilizers. The method involved a simple solid-liquid extraction step using the combination of acetonitrile and McIlvaine buffer as extraction solvent, followed by cleanup with a solid-phase extraction cartridge containing polymeric mixed-mode anion-exchange sorbents. Ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was used to separate and detect target analytes. We particularly focused on the optimization of sample clean-up step: different diluents and dilution factors were tested. The developed method was validated in terms of linearity, recovery, precision, sensitivity and specificity. The recoveries of all the drugs ranged from 70.9% to 112.7% at three concentration levels, with the intra-day and inter-day relative standard deviation lower than 15.7%. The limits of quantification were between 1.0 and 10.0μg/kg for all the drugs. Matrix effect was minimized by matrix-matched calibration curves. The analytical method was successfully applied for the survey of veterinary drugs contamination in 20 compost samples. The results indicated that fluoroquinolones had higher incidence rate and mean concentration levels ranging from 31.9 to 308.7μg/kg compared with other drugs. We expect the method will provide the basis for risk assessment of veterinary drugs in organic fertilizers. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Bioequivalence of generic and branded amoxicillin capsules in healthy human volunteers.

    Science.gov (United States)

    Pathak, Priyanka; Pandit, Vijaya A; Dhande, Priti P

    2017-01-01

    The Medical Council of India urges doctors to prescribe generic drugs as far as possible. The Indian Medical Association had responded earlier saying that it requires guarantees on the quality of generic forms of drugs. Although no published scientific reports are available on the issue of therapeutic inequivalence, unconfirmed clinician accounts and newspaper reports of therapeutic inequivalence exist. This study was planned to ascertain whether bioequivalence of branded and generic amoxicillin capsule is comparable. An open-label, randomized, single-dose, two-treatment, two-sequence, two-period crossover oral bioequivalence study was conducted in 12 healthy, adult human subjects under fasting condition. Serum samples, collected at 8 time points, were analyzed by a validated ultraviolet spectrophotometer method. Pharmacokinetic (PK) parameters such as area under the curve (AUC)0-t, AUC0-∞, Cmax, and Tmax were determined along with time above minimum inhibitory concentration (MIC). The log-transformed PK parameters (Cmax, AUC0-t, AUC0-∞) were analyzed using a Two One-Sided Test ANOVA in SAS for each parameter. Tmax and MIC were analyzed by Wilcoxon rank-sum test in GraphPad Prism. Geometric mean ratio of Cmax fell within bioequivalence criteria. The upper and lower confidence limits of both AUC0-t and AUC0-∞ geometric mean ratio fell below bioequivalence criteria. Time above MIC of generic preparation was significantly lower than that of branded version. The generic capsule was not bioequivalent to the branded amoxicillin capsule.

  4. The utility of in vitro trials that use Caco-2 cell systems as a replacement for animal intestinal permeability and human bioequivalence measurements in drug development

    Directory of Open Access Journals (Sweden)

    Margarida Estudante

    2015-04-01

    Full Text Available Caco-2 cells have been widely used for in vitro intestinal permeability screening of new molecules in drug development but with some pitfalls. Limiting the application of Caco-2 permeability screening to passive compounds is difficult as the majority of approved drugs include both passive diffusion and active transport. The aim of this study was to evaluate Caco-2 cells utility in assessing effects of P-gp mediated efflux. For that purpose the study design included the highly soluble, highly permeable (class 1, verapamil and diltiazem, the highly soluble and poorly permeable drug (class 3 digoxin and the P-gp inhibitor GG918. The apparent permeability and efflux ratio (ER were calculated. Digoxin, a positive control for P-gp, presented an ER of 4, which decreased to around 1 by GG918 addition, consistent with a P-gp effect in Caco-2 cells. ER for verapamil and diltiazem was nearly 1 and the presence of GG918 resulted in no ERs changes. These results suggest that P-gp apparently plays a minimal role in transport of class 1 drugs across Caco-2 cells while class 3 drugs should be significantly affected by P-gp. It is suggested that Caco-2 cells may be useful to determine whether P-gp plays a relevant role in intestinal absorption.

  5. In Vitro Research Tools in the Field of Human Immediate Drug Hypersensitivity and Their Present Use in Small Animal Veterinary Medicine

    Science.gov (United States)

    Lavergne, Lavergne S.

    2016-01-01

    Drug hypersensitivity reactions (DHR) are immune-mediated idiosyncratic adverse drug events. Type I DHR are often referred to as “immediate” and involve B lymphocyte-secreted IgE that bind to the membrane of basophils and mast cells, inducing their degranulation. This review presents various in vitro tests that were developed in the field of human type I HS and implemented as clinical diagnostic tools in human cases of immediate DHR. The respective strengths and weaknesses of each test will be discussed in parallel of validation data such as specificity and sensitivity whenever available. Some of them have also been used as diagnostic tools in veterinary medicine, but not in cases of immediate DHR. Most of these diagnostic tools can be categorized into humoral and cellular tests. The former tests measure serum concentrations of factors, such as histamine, tryptase, and drug-specific IgE. The latter assays quantify markers of drug-induced basophil activation or drug-specific lymphocyte proliferation. Pharmacogenetic markers have also been investigated in immediate DHR, but not as extensively as in non-immediate ones. Throughout, practical aspects and limitations of the tests, as well as sensitivity and specificity parameters, will be presented. In addition, the experience of veterinary medicine with these diagnostic tools will be summarized. However, to date, none of them has ever been reported in a veterinary case of type I DHR. PMID:29056660

  6. VETSTAT - the Danish system for surveillance of the veterinary use of drugs for production animals

    DEFF Research Database (Denmark)

    Stege, H.; Bager, Flemming; Jacobsen, Erik

    2003-01-01

    The Danish Ministry of Food, Agriculture and Fisheries funds a monitoring system based on drug usage information collected at the herd level: VETSTAT. VETSTAT is constructed as a relational database and data originates from three sources: pharmacies, veterinarians and feed mills. All administration...

  7. 21 CFR 530.5 - Veterinary records.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Veterinary records. 530.5 Section 530.5 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS EXTRALABEL DRUG USE IN ANIMALS General Provisions § 530.5 Veterinary records...

  8. Adjusted indirect treatment comparisons of bioequivalence studies

    NARCIS (Netherlands)

    Gwaza, L

    2016-01-01

    Generic medicines are approved by regulatory authorities based on demonstration of bioequivalence with the innovator, however, current regulatory systems do not require direct comparison between all available generics of the same innovator to ensure interchangeability. As such, interchangeability

  9. 77 FR 7585 - Draft Guidance for Industry on Bioequivalence Recommendations for Rifaximin Tablets; Availability

    Science.gov (United States)

    2012-02-13

    ... represent the Agency's current thinking on the design of BE studies to support ANDAs for rifaximin-200 and... specific guidance on the design of bioequivalence (BE) studies to support abbreviated new drug applications... the process that would be used to make product-specific BE recommendations available to the public on...

  10. 78 FR 46965 - Draft Guidance for Industry on Bioequivalence Recommendations for Mesalamine Rectal Suppositories...

    Science.gov (United States)

    2013-08-02

    ..., will represent the Agency's current thinking on the design of BE studies to support ANDAs for... provide specific guidance on the design of bioequivalence (BE) studies to support abbreviated new drug...,'' which explained the process that would be used to make product-specific BE recommendations available to...

  11. Simultaneous determination of multi-class veterinary drugs in chicken processed foods and muscle using solid-supported liquid extraction clean-up.

    Science.gov (United States)

    Yoshikawa, Souichi; Nagano, Chieko; Kanda, Maki; Hayashi, Hiroshi; Matsushima, Yoko; Nakajima, Takayuki; Tsuruoka, Yumi; Nagata, Marie; Koike, Hiroshi; Sekimura, Kotaro; Hashimoto, Tsuneo; Takano, Ichiro; Shindo, Tetsuya

    2017-07-01

    We developed a simultaneous determination method for 37 veterinary drugs in two chicken processed foods (deep-fried chicken and non-fried chicken cutlet) and muscle via liquid chromatography-mass spectrometry. The veterinary drugs belong to 7 different classes, including 4 antifolics, 4 benzimidazoles, 5 macrolides, 7 polyethers, 2 quinolones, 7 sulfonamides, and 8 other classes. The samples were extracted with ethyl acetate followed by acetonitrile with salt and buffers extraction. The two-step extraction enabled analyte extraction from highly lipid samples. The clean-up procedure, a solid-supported liquid extraction clean-up using a diatomaceous earth mini-cartridge, eliminated lipid co-extraction. The prepared sample matrix did not have an effect on the 36 analytes. The method was validated in accordance with the requirements of Japanese validation guidelines. Almost all targeted veterinary drugs successfully satisfied the guideline criteria in the three types of food matrices. The method exhibited recoveries of 70-105%, and the precision of repeatability and within-laboratory reproducibility ranged from 1 to 11% and 1 to 15%, respectively. The limits of quantification were estimated to range from 0.2 to 1.0μg/kg. Applying this method to samples commercially available in Tokyo, residues were detected in 3 out of 26 deep-fried chickens, 5 out of 20 non-fried chicken cutlets, and 17 out of 39 chicken muscles. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Bioequivalence assessment of two formulations of ibuprofen

    KAUST Repository

    Al-Talla, Zeyad

    2011-10-19

    Background: This study assessed the relative bioavailability of two formulations of ibuprofen. The first formulation was Doloraz , produced by Al-Razi Pharmaceutical Company, Amman, Jordan. The second forumulation was Brufen , manufactured by Boots Company, Nottingham, UK. Methods and results: A prestudy validation of ibuprofen demonstrated long-term stability, freeze-thaw stability, precision, and accuracy. Twenty-four healthy volunteers were enrolled in this study. After overnight fasting, the two formulations (test and reference) of ibuprofen (100 mg ibuprofen/5 mL suspension) were administered as a single dose on two treatment days separated by a one-week washout period. After dosing, serial blood samples were drawn for a period of 14 hours. Serum harvested from the blood samples was analyzed for the presence of ibuprofen by high-pressure liquid chromatography with ultraviolet detection. Pharmacokinetic parameters were determined from serum concentrations for both formulations. The 90% confidence intervals of the ln-transformed test/reference treatment ratios for peak plasma concentration and area under the concentration-time curve (AUC) parameters were found to be within the predetermined acceptable interval of 80%-125% set by the US Food and Drug Administration. Conclusion: Analysis of variance for peak plasma concentrations and AUC parameters showed no significant difference between the two formulations and, therefore, Doloraz was considered bioequivalent to Brufen. 2011 Al-Talla et al, publisher and licensee Dove Medical Press Ltd.

  13. Assessing the bioequivalence of analogues of endogenous substances (‘endogenous drugs’): considerations to optimize study design

    Science.gov (United States)

    Dissanayake, Sanjeeva

    2010-01-01

    BACKGROUND Assessment of the bioequivalence of generic versions of certain reference drugs is complicated by the presence of endogenous levels of said compounds which cannot be distinguished from externally derived compound levels following drug administration. If unaccounted for, the presence of endogenous compound biases towards equivalence in bioequivalence studies of these drugs. Bioequivalence assessments may be complicated further as disposition of the exogenous analogue can be subject to various endogenous processes resulting in nonlinear pharmacokinetics. To overcome these inherent biases a number of different strategies have been employed. AIMS To critically review methods used to overcome confounding biases in bioequivalence studies of ‘endogenous’ drugs. METHODS A literature search of the EMBASE and PubMed databases was performed. RESULTS The following strategies were identified: ablation/modulation of baseline endogenous substance levels; recruitment of ‘substance-deficient’ populations; restriction of dietary intake of the relevant substance; standardization of conditions with the potential to affect relevant homeostatic mechanisms; correction for baseline substance levels; and administration of supra-therapeutic drug doses. CONCLUSIONS On the basis of this review key study design concepts, intended to optimize the design of future bioequivalence studies of these so-called ‘endogenous drugs’, are described. The dual stable isotope method, which could be used in a specific context, is also discussed. PMID:20233194

  14. Molecular Target Homology as a Basis for Species Extrapolation to Assess the Ecological Risk of Veterinary Drugs

    Science.gov (United States)

    Increased identification of veterinary pharmaceutical contaminants in aquatic environments has raised concerns regarding potential adverse effects of these chemicals on non-target organisms. The purpose of this work was to develop a method for predictive species extrapolation ut...

  15. Studies of human and veterinary drugs' fate in environmental solid samples--analytical problems.

    Science.gov (United States)

    Wilga, Joanna; Kot-Wasik, Agata; Namieśnik, Jacek

    2008-08-01

    The improvement of medical care worldwide is one of the reasons for the increasing production of pharmaceutical products. Human medicines are affordable to a greater proportion of the world's population. But a significant amount of used pharmaceuticals can create problems--accessibility to high volume production pharmaceuticals contributes to an increased contamination in the environment and the possibility of adverse effects on humans and animals. Many of these substances and their metabolites end up in the soil, sediments, and sludge. Knowledge regarding the environmental occurrence of pharmaceutical products is increasing, but information in the peer-reviewed literature regarding the fate and effects of most pharmaceuticals is limited. One of the reasons for this lack of data is that, until now, there have been few analytical methods capable of detecting these compounds at the low levels, which might be expected in the environment. This review article covers recent developments in the analysis of pharmaceuticals in environmental solid matrices (including soil, sediments, and sludge). We will report applications of different solid sample extraction methods, and current advances in liquid chromatography coupled with mass spectrometry for detection and identification of selected drugs in sludge, soils, manure, and sediments.

  16. Bioequivalence evaluation of glibenclamide 5-mg tablets: diabenil® and daonil® (in 24 healthy volunteers).

    Science.gov (United States)

    Ghozzi, Hanen; Hammami, Serria; Affes, Hanen; Ksouda, Kamilia; Sahnoun, Zouheir; Hakim, Ahmed; Abid, Mohamed

    2015-02-01

    Prescription of generic products is a way to reduce health expense. Bioequivalence is the most appropriate procedure to evaluate the quality and therapeutic efficacy of a generic product. Generic prescriptions are a strategic choice in Tunisia. We expose in this work, a bioequivalence study witch compare a generic (test) product: DIABENIL* manufactured by a Tunisian pharmaceutical industry Dar Essaidaly to the innovative (reference) product: DAONIL* of Aventis pharma laboratories. The bioequivalence of two glibenclamide 5-mg tablets was determined in healthy human, adult volunteers after a single dose in a randomized cross-over in double blind study. Test and reference were administered to twenty-four healthy volunteers of both sexes after overnight fasting. In total, 15 Blood samples were collected before and following the administration of the drug. Serum concentrations of glibenclamide were determined by validated HPLC method. The pharmacokinetic parameters AUC0t, AUC0 , Cmax and tmax were tested for bioequivalence. All parameters showed bioequivalence between both formulations as their confidence intervals were within the bioequivalence acceptable range of 0.80-1.25 limits. We conclude that the two formulations exhibited comparable pharmacokinetic profiles and that the two products can be considered interchangeable in medical practice.

  17. Activities and influence of veterinary drug marketers on antimicrobial usage in livestock production in Oyo and Kaduna States, Nigeria

    Directory of Open Access Journals (Sweden)

    Olufemi Ernest Ojo

    2017-09-01

    Full Text Available Antimicrobial usage in animals contributes to the emergence of antimicrobial resistant bacterial strains. Investigations were carried out on how the characteristics, knowledge, attitude and practices of antimicrobial marketers influenced antimicrobials usage in animal production in Oyo and Kaduna States, Nigeria. Focus group discussions, in-depth interviews and structured questionnaires were used to gather information about the characteristics and activities of antimicrobial marketers. Overall, 70 (56.9 % of 123 marketers had post-secondary education while 76 (61.8 % were trained on the use of antimicrobials. Eighteen (14.6 % of the marketers were licensed veterinarians. Only 51 (41.5 % marketers displayed adequate knowledge about antimicrobials and antimicrobial usage. Sixty-seven (54.6 % marketers requested a prescription before selling antimicrobials while 113 (91.9 % marketer recommended antimicrobials for use in animals. Two-third of the marketers (66.7 % prescribed antimicrobials without physically examining sick animals but based their prescriptions on verbal reports of clinical signs by farmers and on their personal experience. Marketers with higher educational qualification displayed more adequate knowledge of antimicrobials and antimicrobial usage than those with basic education background only. More years of experience in antimicrobial marketing did not translate to better knowledge on antimicrobial usage. Only 45 (36.6 % respondents were aware of the existence of regulatory agencies monitoring the use of antimicrobials in animals. Farmers ignored the services of veterinarians in the diagnosis and control of animal diseases but resorted to drug marketers for help. Effective communication of existing legislations on antimicrobial usage, improved access to veterinary services and strict enforcement of regulatory policies are recommended for checking non-judicious use of antimicrobial agents in animal production. Sales of

  18. bioequivalence study on two 10% enrofloxacin oral formulations in ...

    African Journals Online (AJOL)

    AONDOVER

    Ratios of Cmax, and AUC0-24(T/R) were 0.91 and 1.29 respectively. These are within the bioequivalence acceptance range. conflox. ®. -vet and kenflox. ® are therefore bioequivalent and interchangeable. Key words: Antibacterial, Bioequivalence, Enrofloxacin, Plasma. INTRODUCTION. Enrofloxacin is a third generation,.

  19. Carryover negligibility and relevance in bioequivalence studies.

    Science.gov (United States)

    Ocaña, Jordi; Sanchez O, Maria P; Carrasco, Josep L

    2015-01-01

    The carryover effect is a recurring issue in the pharmaceutical field. It may strongly influence the final outcome of an average bioequivalence study. Testing a null hypothesis of zero carryover is useless: not rejecting it does not guarantee the non-existence of carryover, and rejecting it is not informative of the true degree of carryover and its influence on the validity of the final outcome of the bioequivalence study. We propose a more consistent approach: even if some carryover is present, is it enough to seriously distort the study conclusions or is it negligible? This is the central aim of this paper, which focuses on average bioequivalence studies based on 2 × 2 crossover designs and on the main problem associated with carryover: type I error inflation. We propose an equivalence testing approach to these questions and suggest reasonable negligibility or relevance limits for carryover. Finally, we illustrate this approach on some real datasets. Copyright © 2015 John Wiley & Sons, Ltd.

  20. Efficiency of the Clinical Veterinary Diagnostic Practices and Drug Choices for Infectious Diseases in Livestock in Bangladesh

    DEFF Research Database (Denmark)

    Haider, Najmul; Khan, S. U.; Islam, A.

    2017-01-01

    As in most low-income countries, adequate laboratory facilities are not available in Bangladesh to assist veterinarians in diagnosing animal diseases. We aimed to determine the efficiency of veterinary diagnoses for two common ruminant diseases in Bangladesh: Peste des petits ruminants (PPR......) and foot-and-mouth disease (FMD). We conducted the study from May 2009 to August 2010 in three government veterinary hospitals where veterinarians collected samples from sick livestock and recorded the presumptive diagnosis on the basis of clinical presentations. Samples were tested for PPR and FMD using...

  1. Development, validation and different approaches for the measurement uncertainty of a multi-class veterinary drugs residues LC-MS method for feeds.

    Science.gov (United States)

    Valese, Andressa Camargo; Molognoni, Luciano; de Souza, Naielly Coelho; de Sá Ploêncio, Leandro Antunes; Costa, Ana Carolina Oliveira; Barreto, Fabiano; Daguer, Heitor

    2017-05-15

    A sensitive method for the simultaneous residues analysis of 62 veterinary drugs in feeds by liquid chromatography-tandem mass spectrometry has been developed and validated in accordance to Commission Decision 657/2002/EC. Additionally, limits of detection (LOD), limits of quantitation (LOQ), matrix effects and measurement uncertainty were also assessed. Extraction was performed for all analytes and respective internal standards in a single step and chromatographic separation was achieved in only 12min. LOQ were set to 0.63-5.00μgkg-1 (amphenicols), 0.63-30.00μgkg-1 (avermectins), 0.63μgkg-1 (benzimidazoles), 0.25-200.00μgkg-1 (coccidiostats), 0.63-200.00μgkg-1 (lincosamides and macrolides), 0.25-5.00μgkg-1 (nitrofurans), 0.63-20.00μgkg-1 (fluoroquinolones and quinolones), 15.00μgkg-1 (quinoxaline), 0.63-7.50μgkg-1 (sulfonamides), 0.63-20.00μgkg-1 (tetracyclines), 0.25μgkg-1 (β-agonists), and 30.00μgkg-1 (β-lactams). The top-down approach was adequate for the calculation of measurement uncertainty for all analytes, except the banned substances, which should be rather assessed by the bottom-up approach. Routine analysis of different types of feeds was then carried out. An interesting profile of residues of veterinary drugs among samples was revealed, enlightening the need for stricter control in producing animals. Among the total of 27 feed samples, 20 analytes could be detected/quantified, ranging from trace levels to very high concentrations. A high throughput screening/confirmatory method for the residue analysis of several veterinary drugs in feeds was proposed as a helpful control tool. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Simultaneous detection for three kinds of veterinary drugs: Chloramphenicol, clenbuterol and 17-beta-estradiol by high-throughput suspension array technology

    Energy Technology Data Exchange (ETDEWEB)

    Liu Nan; Su Pu [Institute of Hygiene and Environmental Medicine, Tianjin 300050 (China); Gao Zhixian [Institute of Hygiene and Environmental Medicine, Tianjin 300050 (China)], E-mail: gaozhx@163.com; Zhu Maoxiang; Yang Zhihua; Pan Xiujie [Institute of Radiation Medicine, Beijing 100850 (China); Fang Yanjun; Chao Fuhuan [Institute of Hygiene and Environmental Medicine, Tianjin 300050 (China)

    2009-01-19

    Suspension array technology for simultaneous detection of three kinds of veterinary drugs, chloramphenicol (CAP), clenbuterol and 17-beta-estradiol has been developed. Conjugates of chloramphenicol and clenbuterol coupled with bovine serum albumin were synthesized and purified. Probes of suspension array were constituted by coupling the three conjugates on the fluorescent microspheres/beads and the microstructures of the beads' surface were observed by scanning electron microscopy which was a direct confirmation for the successful conjugates' coupling. The optimal addition of conjugates and the amounts of antibodies were optimized and selected, respectively. Standard curves were plotted and the coefficient of determination-R{sup 2} was greater than 0.989 which suggested good logistic correlation. The detection ranges for the three veterinary drugs are 40-6.25 x 10{sup 5} ng L{sup -1}, 50-7.81 x 10{sup 5} ng L{sup -1} and 1 x 10{sup 3-}7.29 x 10{sup 5} ng L{sup -1}, respectively and the lowest detection limits (LDLs) of them are 40, 50 and 1000 ng L{sup -1}, respectively. The suspension array is specific and has no significant cross-reactivity with other chemicals. Meanwhile, unknown samples were detected by suspension array and ELISA in comparison with each other. The errors between found and real for the detection of the unknown samples were relatively small to both of the two methods, whereas, the detection ranges of suspension array are broader and sensitive than that of the traditional ELISA. The high-throughput suspension array is proved to be a novel method for multi-analysis of veterinary drugs with simple operation, high sensitivity and low cost.

  3. Simultaneous detection for three kinds of veterinary drugs: chloramphenicol, clenbuterol and 17-beta-estradiol by high-throughput suspension array technology.

    Science.gov (United States)

    Liu, Nan; Su, Pu; Gao, Zhixian; Zhu, Maoxiang; Yang, Zhihua; Pan, Xiujie; Fang, Yanjun; Chao, Fuhuan

    2009-01-19

    Suspension array technology for simultaneous detection of three kinds of veterinary drugs, chloramphenicol (CAP), clenbuterol and 17-beta-estradiol has been developed. Conjugates of chloramphenicol and clenbuterol coupled with bovine serum albumin were synthesized and purified. Probes of suspension array were constituted by coupling the three conjugates on the fluorescent microspheres/beads and the microstructures of the beads' surface were observed by scanning electron microscopy which was a direct confirmation for the successful conjugates' coupling. The optimal addition of conjugates and the amounts of antibodies were optimized and selected, respectively. Standard curves were plotted and the coefficient of determination-R(2) was greater than 0.989 which suggested good logistic correlation. The detection ranges for the three veterinary drugs are 40-6.25x10(5) ng L(-1), 50-7.81x10(5) ng L(-1) and 1x10(3-)7.29x10(5) ng L(-1), respectively and the lowest detection limits (LDLs) of them are 40, 50 and 1000 ng L(-1), respectively. The suspension array is specific and has no significant cross-reactivity with other chemicals. Meanwhile, unknown samples were detected by suspension array and ELISA in comparison with each other. The errors between found and real for the detection of the unknown samples were relatively small to both of the two methods, whereas, the detection ranges of suspension array are broader and sensitive than that of the traditional ELISA. The high-throughput suspension array is proved to be a novel method for multi-analysis of veterinary drugs with simple operation, high sensitivity and low cost.

  4. [Matrix effect and retention efficiency of hydrophilic-lipophilic balance cartridges in multi-residual determination of veterinary drugs in river water].

    Science.gov (United States)

    Lin, Shanshan; Yi, Qitong; Hong, Jiajun; Chen, Meng; Yuan, Dongxing

    2013-10-01

    Matrix effect is an important interfering factor in LC-MS quantitative analysis. In this paper, matrix effects and retention efficiencies of 33 veterinary drugs spiked in river water were studied on hydrophilic-lipophilic balance (HLB) cartridges of 3 brands (Waters, Supelco, and CNW), using LC-MS/MS for detection and reverse osmosis (RO) water as the control under 500-fold concentration. In RO water, only the exogenous matrix effects were observed on three brands of HLB cartridges. Most quinolones and tetracyclines showed positive matrix effects. Estrogens showed negative matrix effects on two brands of HLB cartridges. Sulfonamides were not obviously affected by matrix effects. Chloramphenicols showed negative matrix effects on one brand of HLB cartridge. In river water, matrix effects were different from those of the RO water due to the combined exogenous and endogenous interfering substances. Sulfonamides showed slight matrix effects as those in RO water. Most quinolones and tetracyclines showed positive matrix effects. Chloramphenicols and estrogens showed negative matrix effects. Compared to the external standard method, matrix matched calibration method effectively overcame the matrix effects with better quantitative results. The recoveries of 33 target veterinary drugs spiked in river water at 50 ng/L and 200 ng/L levels were in the ranges of 40.3%-146.0% (Waters), 37.8%-104.2% (Supelco), and 52.9%-150.1% (CNW) with RSDs (n = 4) of 0.2%-14.6%. The results indicated that there was no significant difference in the retention efficiency between the 3 HLB cartridges with the matrix matched calibration method. This study provided supporting data for the HLB cartridge selection in multi-residual determination of the veterinary drugs in river water samples.

  5. Carry-over of veterinary drugs from medicated to non-medicated feeds in commercial feed manufacturing plants

    NARCIS (Netherlands)

    Stolker, A.A.M.; Zuidema, T.; Egmond, van H.J.; Deckers, E.R.; Herbes, R.; Hooglught, J.; Olde Heuvel, E.; Jong, de J.

    2013-01-01

    Different compound feeds have to be manufactured in the same production line. As a consequence, traces of the first produced feed may remain in the production and get mixed with the next feed batches. This "carry-over" is unavoidable, and so non-medicated feed can be contaminated with veterinary

  6. Relative bioequivalence of amoxicillin dissolved in breast milk.

    Science.gov (United States)

    Yazdani-Brojeni, Parvaneh; Garcia-Bournissen, Facundo; Fujii, Hisaki; Tanoshima, Reo; Ito, Shinya

    2014-03-01

    Oral antibiotics use in infants in developing countries is challenging because liquid formulations are often unavailable. However, dissolving solid formulation of drugs in water poses a risk of gastrointestinal infection. Although mother's milk may be a potential vehicle, no evidence exists to indicate that antibiotics dissolved in human milk are bioequivalent to those dissolved in water. Therefore, we compared pharmacokinetic parameters of an orally administered antibiotic, amoxicillin, dissolved in human milk, to those of water-dissolved amoxicillin. A pharmacokinetic study was conducted in 16 healthy adult volunteers in a randomised crossover design. Marketed amoxicillin powder for suspension was dissolved in either human milk or water at a final concentration of 50 mg/mL, and 10 mL was given orally in a fasting state. Timed blood samples were obtained and plasma amoxicillin was quantified using liquid chromatography-mass spectrometry. Results showed that pharmacokinetic parameters, including area-under-the-curve, Cmax and half-life of the water-based and milk-based amoxicillin administration were not significantly different. 90% CIs of the ratios of these parameters in concomitant breast milk administration to those of water were within 89% and 116%, suggesting they are bioequivalent (defined as a range between 80% and 125%). We conclude that oral administration of amoxicillin dissolved in human milk at 50 mg/mL results in pharmacokinetics profiles comparable to amoxicillin dissolved in water. Pharmaceutical interactions between amoxicillin and breast milk are unlikely, suggesting no need to modify dosing schedules.

  7. A perspective for biowaivers of human bioequivalence studies on the basis of the combination of the ratio of AUC to the dose and the biopharmaceutics classification system.

    Science.gov (United States)

    Sakuma, Shinji; Tachiki, Hidehisa; Uchiyama, Hitoshi; Fukui, Yasunobu; Takeuchi, Naohiro; Kumamoto, Kazuo; Satoh, Tomonori; Yamamoto, Yoshinobu; Ishii, Emi; Sakai, Yoshiyuki; Takeuchi, Susumu; Sugita, Masaru; Yamashita, Shinji

    2011-08-01

    The ratio of AUC to the dose (AUC/dose) was previously found as a parameter that predicts a risk of bioinequivalence of oral drug products. On the basis of the combination of this parameter and the biopharmaceutics classification system (BCS), a perspective for biowaivers of human bioequivalence studies is discussed. Databases of bioequivalence studies using immediate-release solid oral dosage forms were disclosed by 6 Japanese generic pharmaceutical companies, and the number of subjects required for demonstrating bioequivalence between generic and reference products was plotted as a function of AUC/dose for each BCS category. A small variation in the number of subjects was constantly observed in bioequivalence studies using dosage forms containing an identical BCS class 1 or class 3 drug, even though formulations of the generic product differ between companies. The variation was extremely enlarged when the drugs were substituted with BCS class 2 drugs. Rate-determining steps in oral absorption of highly water-soluble BCS class 1 and class 3 drugs are independent of formulations when there is no significant difference in the in vitro dissolution profiles between formulations. The small variation observed for both BCS categories indicates that the number of subjects converges into one value for each drug. Our analysis indicates the appropriateness of biowaiver of bioequivalence studies for immediate-release solid oral dosage forms containing not only BCS class 1 drugs but also class 3 drugs.

  8. Complexity of intravenous iron nanoparticle formulations: implications for bioequivalence evaluation.

    Science.gov (United States)

    Pai, Amy Barton

    2017-11-01

    Intravenous iron formulations are a class of complex drugs that are commonly used to treat a wide variety of disease states associated with iron deficiency and anemia. Venofer® (iron-sucrose) is one of the most frequently used formulations, with more than 90% of dialysis patients in the United States receiving this formulation. Emerging data from global markets outside the United States, where many iron-sucrose similars or copies are available, have shown that these formulations may have safety and efficacy profiles that differ from the reference listed drug. This may be attributable to uncharacterized differences in physicochemical characteristics and/or differences in labile iron release. As bioequivalence evaluation guidance evolves, clinicians should be educated on these potential clinical issues before a switch to the generic formulation is made in the clinical setting. © 2017 New York Academy of Sciences.

  9. Comparative bioequivalence assessment of aspirin tablets marketed ...

    African Journals Online (AJOL)

    Purpose: In the last few years, aspirin has become a life saver against cardiovascular accidents. This investigation was carried out to determine possible bioequivalence between regular aspirin and soluble aspirin tablets marketed in Nigeria. Methods: The in vivo bioavailability profiles of three commercial brands of aspirin ...

  10. Bioequivalence approach for whole effluent toxicity testing

    Energy Technology Data Exchange (ETDEWEB)

    Shukla, R.; Wang, Q.; Fulk, F.; Deng, C.; Denton, D.

    2000-01-01

    Increased use of whole effluent toxicity (WET) tests in the regulatory arena has brought increased concern over the statistical analysis of WET test data and the determination of toxicity. One concern is the issue of statistical power. A number of WET tests may pass the current hypothesis test approach because they lack statistical power to detect relevant toxic effects because of large within-test variability. Additionally, a number of WET tests may fail the current approach because they possess excessive statistical power, as a result of small within-test variability, and detect small differences that may not be biologically relevant. The strengths and limitations of both the traditional hypothesis test approach and the bioequivalence approach for use in the National Pollutant Discharge Elimination System program were evaluated. Data from 5,213 single-concentration, short-term chronic WET tests with Ceriodaphnia dubia provided the database for analysis. Comparison of results between the current approach and the bioequivalence approach indicates that the current approach to WET testing is generally sound but that adopting the proposed bioequivalence approach resolves concerns of statistical power. Specifically, within this data set, applying the bioequivalence approach resulted in failure for tests with relatively large test variability and a pass for tests with relatively small within-test variability.

  11. Topical bioequivalence of acyclovir creams using dermal microdialysis in pigs: a new model to evaluate bioequivalence for topical formulations.

    Science.gov (United States)

    Wei, Huilin; Wang, Shuqi; Xu, Feng; Xu, Lanfang; Zheng, Jiarun; Chen, Yun

    2012-07-01

    The aim was to evaluate the bioequivalence of topically applied Acyclovir (ACV) creams using dermal microdialysis (DMD) in a pig model. Three ACV creams (3%), ACV1, ACV2 and ACV3, were topically administrated on the dorsum of pigs, and the DMD sampling technique was used to continuously collect microdialysate. The concentration of ACV in microdialysate was measured by HPLC and the concentration-time profiles were used to calculate pharmacokinetic parameters. The results showed that 90% confidence interval (CI) of the ratio of AUC(0-4 h) of ACV2 and ACV3 was between 88.2 and 105.7%, which was within the acceptance range (80-125%). Ninety percent CI of the ratio of C(max) of ACV2 and ACV3 was between 87.4 and 124.4%, which was within the acceptance range (80-125%). These data indicate that ACV2 and ACV3 used in this study were bioequivalent. This study demonstrates that the pig model coupled with DMD sampling can potentially provide a cost-effective strategy to evaluate topical drug delivery and its associated pharmacokinetic studies.

  12. Recommendations for Clinical Pathology Data Generation, Interpretation, and Reporting in Target Animal Safety Studies for Veterinary Drug Development.

    Science.gov (United States)

    Siska, William; Gupta, Aradhana; Tomlinson, Lindsay; Tripathi, Niraj; von Beust, Barbara

    Clinical pathology testing is routinely performed in target animal safety studies in order to identify potential toxicity associated with administration of an investigational veterinary pharmaceutical product. Regulatory and other testing guidelines that address such studies provide recommendations for clinical pathology testing but occasionally contain outdated analytes and do not take into account interspecies physiologic differences that affect the practical selection of appropriate clinical pathology tests. Additionally, strong emphasis is often placed on statistical analysis and use of reference intervals for interpretation of test article-related clinical pathology changes, with limited attention given to the critical scientific review of clinically, toxicologically, or biologically relevant changes. The purpose of this communication from the Regulatory Affairs Committee of the American Society for Veterinary Clinical Pathology is to provide current recommendations for clinical pathology testing and data interpretation in target animal safety studies and thereby enhance the value of clinical pathology testing in these studies.

  13. Analysis of Veterinary Drug and Pesticide Residues Using the Ethyl Acetate Multiclass/Multiresidue Method in Milk by Liquid Chromatography-Tandem Mass Spectrometry

    Directory of Open Access Journals (Sweden)

    Husniye Imamoglu

    2016-01-01

    Full Text Available A rapid and simple multiclass, ethyl acetate (EtOAc multiresidue method based on liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS detection was developed for the determination and quantification of 26 veterinary drugs and 187 total pesticide residues in milk. Sample preparation was a simple procedure based on liquid–liquid extraction with ethyl acetate containing 0.1% acetic acid, followed by centrifugation and evaporation of the supernatant. The residue was dissolved in ethyl acetate with 0.1% acetic acid and centrifuged prior to LC-MS/MS analysis. Chromatographic separation of analytes was performed on an Inertsil X-Terra C18 column with acetic acid in methanol and water gradient. The repeatability and reproducibility were in the range of 2 to 13% and 6 to 16%, respectively. The average recoveries ranged from 75 to 120% with the RSD (n=18. The developed method was validated according to the criteria set in Commission Decision 2002/657/EC and SANTE/11945/2015. The validated methodology represents a fast and cheap alternative for the simultaneous analysis of veterinary drug and pesticide residues which can be easily extended to other compounds and matrices.

  14. Target analysis and retrospective screening of veterinary drugs, ergot alkaloids, plant toxins and other undesirable substances in feed using liquid chromatography-high resolution mass spectrometry.

    Science.gov (United States)

    León, Nuria; Pastor, Agustín; Yusà, Vicent

    2016-01-01

    A comprehensive strategy combining a quantitative method for 77 banned veterinary drugs, mycotoxins, ergot alkaloids and plant toxins, and a post-target screening for 425 substances including pesticides and environmental contaminants in feed were developed using a QuEChERS-based extraction and an ultra-high performance liquid chromatography coupled to high-resolution mass spectrometry (UHPLC-HRMS). The quantitative method was validated after previous statistical optimisation of the main parameters governing ionisation, and presented recoveries ranging, in general, from 80 to 120%, with a precision in terms of Relative Standard Deviation (RSD) lower than 20%. The full-scan accurate mass data were acquired with a resolving power of 50000 FWHM and a mass accuracy lower than 5ppm. The method LOQ was lower than 12.5µgkg(-1) for the majority of the veterinary drugs and plant toxins and 20µgkg(-1) for ergot alkaloids. For post-target screening a customised theoretical database including the exact mass, the polarity of acquisition and the expected adducts was built and used for post-run retrospective screening. The analytical strategy was applied to 32 feed samples collected from farms of the Valencia Region (Spain). Florfenicol, zearalenone and atropine were identified and quantified at concentrations around 10µgkg(-1). In the post-target screening of the real samples, Sulfadiazine, Thrimetoprin and Pirimiphosmethyl were tentatively identified. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Wide-scope analysis of pesticide and veterinary drug residues in meat matrices by high resolution MS: detection and identification using Exactive-Orbitrap.

    Science.gov (United States)

    Gómez-Pérez, María Luz; Romero-González, Roberto; Plaza-Bolaños, Patricia; Génin, Eric; Martínez Vidal, José Luis; Garrido Frenich, Antonia

    2014-01-01

    A multiresidue and multiclass method for the simultaneous determination of more than 350 compounds including pesticides, biopesticides and veterinary drugs in different meat matrices (beef, pork and chicken) by ultra-high performance liquid chromatography coupled to Orbitrap MS has been developed. In the present study, the determination of fragments was accomplished as an essential tool for a reliable identification of compounds using high resolution MS. To obtain these fragments, different strategies have been carried out in order to ensure an appropriate fragment assignment and identification. The analytical method is suitable for qualitative analysis, and it was also evaluated for quantitative analysis. Generic extraction conditions were optimized, obtaining adequate recovery and precision values for most of the studied analytes (>290). The limits of detection ranged from 2 to 16 µg kg(-1). Limits of quantification were 10 µg kg(-1) with the exception of few compounds with a higher value (50 or 100 µg kg(-1)). Limits of identification were also established, and they ranged from 2 to 150 µg kg(-1). This method was applied to the analysis of 18 meat samples and some veterinary drugs as enrofloxacin and sulfadiazine were detected and further identified/quantified (with triple quadrupole) in two different samples at 33 µg kg(-1) and trace levels, respectively. No pesticides were detected in the analyzed samples. Copyright © 2014 John Wiley & Sons, Ltd.

  16. Analysis of veterinary drug residues in frog legs and other aquacultured species using liquid chromatography quadrupole time-of-flight mass spectrometry.

    Science.gov (United States)

    Turnipseed, Sherri B; Clark, Susan B; Storey, Joseph M; Carr, Justin R

    2012-05-09

    A liquid chromatography quadrupole time-of-flight (Q-TOF) mass spectrometry method was developed to analyze veterinary drug residues in frog legs and other aquacultured species. Samples were extracted using a procedure based on a method developed for the analysis of fluoroquinolones (FQs) in fish. Briefly, the tissue was extracted with dilute acetic acid and acetonitrile with added sodium chloride. After centrifugation, the extracts were evaporated and reconstituted in mobile phase. A molecular weight cutoff filter was used to clean up the final extract. A set of target compounds, including trimethoprim, sulfamethoxazole, chloramphenicol, quinolones, and FQs, was used to validate the method. Screening of residues was accomplished by collecting TOF (MS¹) data and comparing the accurate mass and retention times of compounds to a database containing information for veterinary drugs. An evaluation of the MS data in fortified frog legs indicated that the target compounds could be consistently detected at the level of concern. The linearity and recoveries from matrix were evaluated for these analytes to estimate the amount of residue present. MS/MS data were also generated from precursor ions, and the mass accuracy of the product ions for each compound was compared to theoretical values. When the method was used to analyze imported frog legs, many of these residues were found in the samples, often in combination and at relatively high concentrations (>10 ng/g). The data from these samples were also evaluated for nontarget analytes such as residue metabolites and other chemotherapeutics.

  17. Comprehensive qualitative and quantitative determination of pesticides and veterinary drugs in honey using liquid chromatography-Orbitrap high resolution mass spectrometry.

    Science.gov (United States)

    Gómez-Pérez, María Luz; Plaza-Bolaños, Patricia; Romero-González, Roberto; Martínez-Vidal, José Luis; Garrido-Frenich, Antonia

    2012-07-27

    A database has been created for the simultaneous analysis of more than 350 pesticides and veterinary drugs (including antibiotics) using ultra-high performance liquid chromatography coupled to high resolution Orbitrap mass spectrometry (UHPLC-Orbitrap-MS). This is a comprehensive exact mass database built using the Exactive-Orbitrap analyzer. The developed database includes exact masses of the target ions and retention time data, and allows the automatic search of the included compounds. Generic chromatographic and MS conditions have been applied. The presented database is suitable for qualitative analysis, and it was also evaluated for quantitative purposes in routine analysis, after the optimization and validation of a generic extraction method in honey samples. Adequate recovery and precision values for most of the studied analytes were obtained and the limits of detection (LOD) ranged from 1 to 50 μg kg(-1). For pesticides, LODs were always lower than the MRLs established by European Union in honey, except for a few compounds. This method was applied to the analysis of 26 real honey samples and some pesticides (azoxystrobin, coumaphos, dimethoate and thiacloprid) were detected in 4 samples. Azoxystrobin and coumaphos were determined in two different samples (organic honey) at 1.5 μg kg(-1) and 5.1 μg kg(-1). Veterinary drugs were not detected in the analyzed samples. Copyright © 2012 Elsevier B.V. All rights reserved.

  18. Fluconazole bioequivalence study: quantification by tandem mass spectrometry.

    Science.gov (United States)

    Moraes, L A; Lerner, F E; Moraes, M E; Moraes, M O; Corso, G; De Nucci, G

    1999-04-01

    To develop a new method for quantifying fluoconazole in human plasma and to compare the bioavailability of two fluconazole capsule formulations, an open, randomized, two-period crossover study with a one-week washout interval was conducted in 24 healthy volunteers. Plasma samples were obtained up to 168 hours after drug administration and the serum fluconazole concentrations were analyzed using electrospray tandem mass spectrometry coupled to liquid chromatography using multiple reaction monitoring mode. The pharmacokinetic parameters obtained for fluconazole after the administration of each formulation included the Area under the curve (AUC)(0-168h), AUC(0-infinity), Cmax, Cmax/AUC(0-168h), Tmax, elimination rate constant (Ke), and half-life (T1/2). Within- and between-run imprecision was less than 2.3% and 8.2%, respectively. Inaccuracy within and between runs was -1.5% and -9.7%, respectively. The pharmacokinetic parameters for bioequivalence showed a normal distribution, and the variance of AUC(0-168h), AUC(0-infinity), and Cmax were homoscedastic. The geometric mean for the Fluconal/Zoltec (Fluconal; Libbs Farmacêutica Ltda, São Paulo, Brazil; Zoltec; Laboratórios Pfizer Ltda., São Paulo, Brazil) individual percent ratio was 94.9% for AUC(0-168h), 94.7% for AUC(0-infinity), 80.1% for Cmax, 102.6% for Ke, 97.5% for T1/2, and 0.93 for Tmax (arithmetic mean of individual differences). We have developed a method in which liquid chromatography is coupled with electrospray tandem mass spectrometry to improve the pharmacokinetic analysis of fluconazole. Because the 90% CI AUC is within the interval proposed for the Food and Drug Administration, we concluded that Fluconal is bioequivalent to Zoltec in terms of absorption. The CV was 27.5% for the Cmax parameter, indicating that fluconazole's absorption rate is highly variable. The European Union Regulatory Agency accepts an interval of 70-143%, and because the 90% CI for Cmax is within the interval proposed for

  19. Targeting the environmental assessment of veterinary drugs with the multi-species-soil system (MS{center_dot}3) agricultural soil microcosms: the ivermectin case study

    Energy Technology Data Exchange (ETDEWEB)

    Carbonell-Martin, G.; Pro-Gonzalez, J.; Aragones-Grunert, P.; Babib-Vich, M. M.; Fernandez-Rorija, C.; Tarazona-Lafarga, J. V.

    2011-07-01

    The environmental risk assessment of the veterinary pharmaceutical ivermectin is receiving significant attention. This paper assesses the capacity of the MS{center_dot}3 soil microcosm as a tool for targeting the environmental impact assessment of veterinary drugs, using ivermectin as model. Two screening MS{center_dot}3 were performed using different European soils; one with a soil collected in an agricultural station near to Madrid, Spain and a second with a soil collected in a farm area close to York, UK. Soils were fortified with ivermectin at the following ranges: 0.01-10 mg kg{sup -}1 and 0.1-100 mg kg{sup -}1 in the Madrid and York studies, respectively. The effects on earthworms, plants and soil microorganisms were assessed in the Madrid soil. Toxicity tests on aquatic organisms (algae, cladocerans and in vitro fish cell line RTLW1) were also conducted with the leachates. No effects were observed in earthworms and plants at any tested concentration; reduction in the respiration rate (< 5%) of soil microorganisms was detected. Earthworm/soil bioconcentration factors decreased with the increase in soil concentrations and were higher for the York soil. Effects on daphnids were observed in tested leachates; based on measured levels of ivermectin in the leachates an EC50 of about 0.5{mu}gL{sup -}1 can be estimated. Comparisons based on toxicity data and equilibrium partitioning confirmed that the main risk is expected to be related to the high sensitivity of cladocerans. The results confirm that MS{center_dot}3 systems are cost-effective tools for assessing the impact of veterinary pharmaceuticals when applied to agricultural land, as previously demonstrated for antimicrobials. (Author) 39 refs.

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

    Directory of Open Access Journals (Sweden)

    Hui-Ru Chen

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

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

    Science.gov (United States)

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

    2017-05-15

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

  2. Veterinary Parasitology

    OpenAIRE

    Rondon, F. C. M.; Bevilaqua, C.M.L.; Franke,C.R.; Barros, R. S.; Oliveira,F.R.; Alcântara, Adriano Costa de; Diniz, A. T.

    2008-01-01

    Acesso restrito: Texto completo. p. 24-31 Visceral leishmaniasis (VL) is one of the most important reemerging parasitic disease in the world. The domestic dog is the main reservoir in urban environments. The aim of this work was to extend the knowledge on canine Leishmania infection in the city of Fortaleza in northeastern Brazil, identifying the risk factors inherent in dog susceptibility to the infection. Two populations were analyzed, domestic dogs from clinics and the Veterinary ...

  3. Multi-drug-resistant Acinetobacter calcoaceticus-Acinetobacter baumannii complex infection outbreak in dogs and cats in a veterinary hospital.

    Science.gov (United States)

    Kuzi, S; Blum, S E; Kahane, N; Adler, A; Hussein, O; Segev, G; Aroch, I

    2016-11-01

    Members of the Acinetobacter calcoaceticus-Acinetobacter baumannii complex cause severe outbreaks in humans, and are increasingly reported in animals. A retrospective study, describing a severe outbreak in dogs and cats caused by a multidrug resistant member of the Acinetobacter calcoaceticus-Acinetobacter baumannii complex in a veterinary hospital, between July 2010 and November 2012. The study included 19 dogs and 4 cats. Acinetobacter calcoaceticus-Acinetobacter baumannii complex bacteria were isolated from urine (9 animals), respiratory tract (11), tissues (3) and blood (1). The most common infection-associated findings included fever, purulent discharge from endotracheal tubes, hypotension, and neutropaenia. Infections led to pneumonia, urinary tract infection, cellulitis and sepsis. Infection was transmitted in the intensive care unit, where 22 of 23 animals were initially hospitalised. The mortality rate was 70% (16 of 23 animals), and was higher in cases of respiratory infection compared to other infections. Aggressive environmental cleaning and disinfection, with staff education for personal hygiene and antisepsis, sharply decreased the infection incidence. Health care-associated outbreaks with multidrug resistant Acinetobacter calcoaceticus-Acinetobacter baumannii complex in dogs and cats are potentially highly fatal and difficult to eradicate, warranting monitoring, antiseptic techniques and judicious antibiotic use. © 2016 British Small Animal Veterinary Association.

  4. Two-stage designs in bioequivalence trials.

    Science.gov (United States)

    Schütz, Helmut

    2015-03-01

    The aim of this study is to assess the current status of non-fixed sample size designs in bioequivalence trials with a focus on two-stage adaptive approaches. We searched PubMed and Google Scholar from inception to October 2014. Regulatory guidelines were obtained from the public domain. Different methods were compared by Monte Carlo simulations for their impact on the patient's and producer's risks. Add-on designs, group sequential designs and adaptive two-stage sequential designs are currently accepted to demonstrate bioequivalence in various regulations. All three approaches may inflate the patient's risk if applied inconsiderately. Direct transfer of methods developed for superiority testing to bioequivalence is not warranted. Published two-stage frameworks maintain the type I error and generally the desired power. Adaptation based on the observed T/R ratio observed in the first stage should be applied with caution. Monte Carlo simulations are an efficient tool to explore the operating characteristics of methods. Validated two-stage frameworks can be applied without requiring the sponsor to perform own simulations-which could further improve power based on additional assumptions. Two-stage designs are both ethical and economical alternatives to fixed sample designs.

  5. Qualitative Multiresidue Screening Method for 143 Veterinary Drugs and Pharmaceuticals in Milk and Fish Tissue Using Liquid Chromatography Quadrupole-Time-of-Flight Mass Spectrometry.

    Science.gov (United States)

    Dasenaki, Marilena E; Bletsou, Anna A; Koulis, George A; Thomaidis, Nikolaos S

    2015-05-13

    A wide-scope screening methodology has been developed for the identification of veterinary drugs and pharmaceuticals in fish tissue and milk using ultrahigh-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-QTOF MS). The method was validated using a qualitative approach at two concentration levels. The detection of the residues was accomplished by retention time, accurate mass, and the isotopic fit using an in-house database. Product-ion spectra were used for unequivocal identification of the compounds. Generic sample treatment was applied. The majority of the compounds were successfully detected and identified at concentration levels of 150 ng mL(-1) in milk and 200 μg kg(-1) in fish (>80% of the compounds in both matrices), whereas satisfactory results were also obtained at concentration levels of 15 ng mL(-1) in milk and 20 μg kg(-1) in fish (>60% of the compounds detected and identified).

  6. Bioequivalence Between Generic and Branded Lamotrigine in People With Epilepsy: The EQUIGEN Randomized Clinical Trial.

    Science.gov (United States)

    Berg, Michel; Welty, Timothy E; Gidal, Barry E; Diaz, Francisco J; Krebill, Ron; Szaflarski, Jerzy P; Dworetzky, Barbara A; Pollard, John R; Elder, Edmund J; Jiang, Wenlei; Jiang, Xiaohui; Switzer, Regina D; Privitera, Michael D

    2017-08-01

    Switching between generic antiepileptic drugs is a highly debated issue that affects both clinical care and overall health care costs. To evaluate the single-dose pharmacokinetic bioequivalence of 3 (1 branded and 2 generic drugs) on-market, immediate-release lamotrigine drug products. The Equivalence Among Antiepileptic Drug Generic and Brand Products in People With Epilepsy (EQUIGEN) single-dose study is a crossover, prospective, sequence-randomized, replicate pharmacokinetic study conducted at 5 US academic epilepsy centers. Fifty adults (≥18 years) with epilepsy who were taking concomitant antiepileptic drugs and not currently receiving lamotrigine were enrolled between July 18, 2013, and January 19, 2015. Every participant was randomly assigned to 1 of 3 equivalent sequences, each comprising 6 study periods, during which they had blood draws before and after medication administration. Forty-nine participants were included in intention-to-treat analyses. Participants received a single 25-mg dose of immediate-release lamotrigine at the start of each period, with the branded and the 2 most disparate generic products each studied twice. Lamotrigine was selected as the antiepileptic drug of interest because of its wide use, publications indicating problems with generic switches, and complaints to the US Food and Drug Administration regarding generic products. Both participants and study personnel were blinded to the specific generic products selected. The primary outcome was bioequivalence between products. Maximum plasma concentration (Cmax) and area under the concentration-time curve (AUC) were compared, and average bioequivalence (ABE) was established if the 90% CIs of the ratios of the 2 products were within equivalence limits (80%-125%). Of the 50 randomized participants, 49 (98%) received all 3 lamotrigine products and completed at least 3 pharmacokinetic assessments and 46 (92%) completed all 6 pharmacokinetic assessments. Among the 49 participants, 28 (57

  7. Multi-residue determination of 115 veterinary drugs and pharmaceutical residues in milk powder, butter, fish tissue and eggs using liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Dasenaki, Marilena E; Thomaidis, Nikolaos S

    2015-06-23

    A simple and sensitive multi-residue method for the determination of 115 veterinary drugs and pharmaceuticals, belonging in more than 20 different classes, in butter, milk powder, egg and fish tissue has been developed. The method involves a simple generic solid-liquid extraction step (solvent extraction, SE) with 0.1% formic acid in aqueous solution of EDTA 0.1% (w/v)-acetonitrile (ACN)-methanol (MeOH) (1:1:1, v/v) with additional ultrasonic-assisted extraction. Precipitation of lipids and proteins was promoted by subjecting the extracts at very low temperature (-23°C) for 12h. Further cleanup with hexane ensures fat removal from the matrix. Analysis was performed by liquid chromatography coupled with electrospray ionization and tandem mass spectrometry (LC-ESI-MS/MS). Two separate runs were performed for positive and negative ionization in multiple reaction monitoring mode (MRM). Particular attention was devoted to extraction optimization: different sample-to-extracting volume ratios, different concentrations of formic acid in the extraction solvent and different ultrasonic extraction temperatures were tested in butter, egg and milk powder samples. The method was also applied in fish tissue samples. It was validated, on the basis of international guidelines, for all four matrices. Quantitative analysis was performed by means of standard addition calibration. For over 80% of the analytes, the recoveries were between 50% and 120% in all matrices studied, with RSD values in the range of 1-18%. Limits of detection (LODs) and quantification (LOQs) ranged from 0.008 μg kg(-1) (oxfendazole in butter) to 3.15 μg kg(-1) (hydrochlorthiazide in egg). The evaluated method provides reliable screening, quantification, and identification of 115 veterinary drug and pharmaceutical residues in foods of animal origin and has been successfully applied in real samples. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Efficiency of the Clinical Veterinary Diagnostic Practices and Drug Choices for Infectious Diseases in Livestock in Bangladesh.

    Science.gov (United States)

    Haider, N; Khan, S U; Islam, A; Osmani, M G; Rahman, M Z; Epstein, J H; Daszak, P; Zeidner, N S

    2017-08-01

    As in most low-income countries, adequate laboratory facilities are not available in Bangladesh to assist veterinarians in diagnosing animal diseases. We aimed to determine the efficiency of veterinary diagnoses for two common ruminant diseases in Bangladesh: Peste des petits ruminants (PPR) and foot-and-mouth disease (FMD). We conducted the study from May 2009 to August 2010 in three government veterinary hospitals where veterinarians collected samples from sick livestock and recorded the presumptive diagnosis on the basis of clinical presentations. Samples were tested for PPR and FMD using real-time RT-PCR. We estimated the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the presumptive diagnoses when compared to laboratory tests. We tested 539 goats for PPR and 340 cattle and goats for FMD. Our results indicate that the veterinarians' presumptive diagnoses were different from laboratory findings for both PPR (P clinical diagnoses was 54% (95% CI: 47-61%) while specificity was 81% (95% CI: 78-84%) compared to real-time RT-PCR tests. The kappa value obtained in our validation process for PPR (kappa: 0.25) and FMD (kappa 0.36) indicated a poor performance of the presumptive diagnoses. Most of the animals (93%) were treated with antibiotics. Our findings indicate that veterinarians can detect animals not infected with FMD or PPR but miss the true cases. The clinical competency of these veterinarians needs to be improved and access to laboratory diagnostic facilities could help veterinarians to improve the diagnostics and outcomes. The rational use of antibiotics by veterinarians in animals must be ensured. © 2016 Blackwell Verlag GmbH.

  9. A bioequivalence study of two omeprazole formulations in healthy male volunteers.

    Science.gov (United States)

    Kim, Yu Kyong; Yoon, Seonghae; Yu, Kyung-Sang; Kim, Bo-Hyung; Yim, Sung-Vin

    2016-11-01

    This study had a single-dose, randomized, open-label, 2-period, and 2-sequence crossover design to evaluate pharmacokinetic (PK) bioequivalence between the test and reference formulations. Of the 34 healthy male volunteers enrolled, 4 were excluded owing to consent withdrawal before drug administration and the remaining 30 subjects were administered 20 mg each of the test and reference formulations of omeprazole. The blood samples for PK analysis were collected at the scheduled time-points, prior to dosing to 10 hours after dosing. Plasma concentrations of omeprazole were quantified by a liquid chromatography-tandem mass spectrometry method. Bioequivalence was assessed according to current guidelines issued by regulatory authorities. The plasma concentration-time profiles of omeprazole were similar between the reference and test drugs. The geometric mean ratios (90% confidence interval: CI) of test to reference were 0.9104 (0.8538 - 0.9708) for peak plasma concentration (Cmax) and 0.9304 (0.8836 - 0.9796) for area under the plasma concentration-time curve from time zero to time of last measureable concentration (AUC0-t). The results from the PK analysis suggested that the reference and test formulations of 20 mg omeprazole capsules were bioequivalent in healthy male subjects.

  10. Pivotal Bioequivalence Study of Clopacin®, a Generic Formulation of Clopidogrel 75 mg Film-Coated Tablets.

    Science.gov (United States)

    McGregor, Gerard Patrick

    2016-02-01

    Clopacin(®) (Acino Pharma AG) is a proprietary, besylate salt and lactose-free formulation of the widely-used anti-platelet treatment, clopidogrel. This study aimed to evaluate the bioequivalence of Clopacin(®) with the originator as reference drug, using a guideline-compliant trial design: open-labeled, randomized, single-dose (clopidogrel 75 mg tablet), two-period, crossover trial in 48 healthy male volunteers, with a 7 day wash-out period. Plasma samples were collected at intervals and extracted before quantifying clopidogrel concentrations using a fully validated LC-MS/MS method. Bioequivalence of Clopacin(®) and the reference drug was established by comparison of the primary pharmacokinetic parameters, C max, AUC0-t, and AUC0-∞. The parameter values were similar for the two products (analysis of variance) and provided Clopacin/reference ratios (least squares means) of >90% and 90% confidence intervals (CIs 84.64-105.50%, 90.43-111.22%, 88.75-110.71%, respectively) that were well within the limits set for defining bioequivalence, according to international guidelines. The respective Clopacin(®) and reference drug values for mean time to maximal plasma clopidogrel concentration (t max) were 0.83 and 0.91 h, and for terminal elimination half-life were 3.99 and 3.51 h. The intra-subject coefficients of variability for maximal plasma clopidogrel concentration (C max), area under the plasma clopidogrel concentration versus time curve, at 48 h (AUC0-t) and extrapolated to infinity (AUC0-∞) were 32.2%, 30.2%, and 28.9% (least square means), respectively, and the respective power values were 99.5%, 97.1%, and 95.3%. This bioequivalence study provided robust clopidogrel pharmacokinetic data that established the bioequivalence of Clopacin(®) and the reference originator drug. Acino Pharma AG (formerly Cimex AG).

  11. Hydrogen bond replacement--unearthing a novel molecular mechanism of surface solid dispersion for enhanced solubility of a drug for veterinary use.

    Science.gov (United States)

    Singh, Deshvir; Pathak, Kamla

    2013-01-30

    The project was aimed to enhance the solubility of ivermectin using surface solid dispersion (SSD), elucidate the mechanism of drug release and to develop its tablet that can draw rapid clinical effects on dogs for controlling Ascaris parasites. Superdisintegrants and adsorbents were used to formulate SSDs by co-evaporation method. Formulation 9th that constituted from drug:aerosil (1:10) was selected after solubility and in vitro dissolution evaluation, and characterized by DSC, XRPD, DRS and SEM analysis. In vitro evaluation and in vivo efficacy of its tablet on dogs (fecal egg and tick counting studies) were compared with marketed tablets. This formulation enhanced the solubility of ivermectin to 456.25±1.70% and released 93.55±0.47% in 60 min. DRS spectral analysis unearthed a novel molecular mechanism of hydrogen bond replacement that drifts the drug into the medium from the surface of the SSD particles. Reduced crystallinity was confirmed by XRPD and supported by SEM. During in vitro and in vivo studies, the formulated tablet showed superiority over marketed tablet with higher parasite inhibition (p<0.001). Thus SSD is a promising technique for enhancing IVM solubility at molecular level enabling its rapid oral delivery to control endo- as well as ectoparasites for veterinary purpose. Copyright © 2012 Elsevier B.V. All rights reserved.

  12. Fluorescence detection of tramadol in healthy Chinese volunteers by high-performance liquid chromatography and bioequivalence assessment

    Directory of Open Access Journals (Sweden)

    Zhou X

    2015-02-01

    Full Text Available Xiao Zhou, Ji Liu Department of Anesthesia, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China Abstract: This study developed a revised high-performance liquid chromatography fluorescence method to determine plasma tramadol concentration, and thereby to examine the bioequivalence of two tramadol formulations among healthy male Chinese volunteers. The study used a double-blind, randomized, 2×2 crossover-design principle. Calculated pharmacokinetic parameters for both formulations were consistent with previous reports. According to the observation of vital signs and laboratory measurement, no subjects had any adverse reactions. The geometric mean ratios (90% confidence interval of the test drug/reference drug for tramadol were 100.2% (95.3%–103.4% for the area under the plasma concentration–time curve (AUC from time zero to the last measurable concentration, 99.6% (94.2%–102.7% for the AUC from administration to infinite time, and 100.8% (93.1%–106.4% for maximum concentration. For the 90% confidence intervals of the test/reference AUC ratio and maximum concentration ratio of tramadol, both were in the acceptance range for bioequivalence. According to the two preparations by pharmacokinetic parameter statistics, the half-life, mean residence time, and clearance values showed no significant statistical differences. Therefore, the conclusion of this study was that the two tramadol formulations (tablets and capsules were bioequivalent. Keywords: tramadol hydrochloride, in vitro release, pharmacokinetic, bioequivalence, fluorescence detector

  13. Bioequivalence study of two formulations of bisoprolol fumarate film-coated tablets in healthy subjects

    Directory of Open Access Journals (Sweden)

    Tjandrawinata RR

    2012-10-01

    Full Text Available Raymond R Tjandrawinata,1 Effi Setiawati,2 Danang Agung Yunaidi,2 Iwan Dwi Santoso,2 Arini Setiawati,3 Liana W Susanto11Dexa Laboratories of Biomolecular Sciences (DLBS, Cikarang, Indonesia; 2Bioavailability and Bioequivalence Laboratory, Equilab International, Jakarta, Indonesia; 3Department of Pharmacology and Therapeutics, University of Indonesia, Jakarta, IndonesiaBackground: The present study was conducted to compare the bioavailability of two bisoprolol fumarate 5 mg film-coated tablet formulations (test and reference formulations.Patients and methods: This study was a randomized, single-blind, two-period, two-sequence crossover study that included 18 healthy adult male and female subjects under fasting condition. The pharmacokinetic parameters were determined based on the concentrations of bisoprolol (CAS 66722-44-9, using ultraperformance liquid chromatography with a tandem mass spectrometer detector. In each of the two study periods (separated by a washout of 1 week a single dose of test or reference product was administered. The pharmacokinetic parameters assessed were area under the plasma concentration-time curve from time zero to 48 hours (AUCt, AUC from time zero to infinity (AUCinf, the peak plasma concentration of the drug (Cmax, time needed to achieve Cmax (tmax, and the elimination half-life (t½.Results: The geometric mean ratios (90% confidence intervals of the test drug/reference drug for bisoprolol were 101.61% (96.14%–107.38% for AUCt, 101.31% (95.66%–107.29% for AUCinf, and 100.28% (93.90%–107.09% for Cmax. The differences between the test and reference drug products for bisoprolol tmax and t½ values were not statistically significant (P > 0.05. There was no adverse event encountered during this bioequivalence test. The 90% confidence intervals of the test/reference AUC ratio and Cmax ratio of bisoprolol were within the acceptance range for bioequivalence.Conclusion: It was concluded that the two bisoprolol film

  14. Nanomedicine in veterinary oncology.

    Science.gov (United States)

    Lin, Tzu-Yin; Rodriguez, Carlos O; Li, Yuanpei

    2015-08-01

    Nanomedicine is an interdisciplinary field that combines medicine, engineering, chemistry, biology and material sciences to improve disease management and can be especially valuable in oncology. Nanoparticle-based agents that possess functions such as tumor targeting, imaging and therapy are currently under intensive investigation. This review introduces the basic concept of nanomedicine and the classification of nanoparticles. Because of their favorable pharmacokinetics, tumor targeting properties, and resulting superior efficacy and toxicity profiles, nanoparticle-based agents can overcome several limitations associated with conventional diagnostic and therapeutic protocols in veterinary oncology. The two most important tumor targeting mechanisms (passive and active tumor targeting) and their dominating factors (i.e. shape, charge, size and nanoparticle surface display) are discussed. The review summarizes published clinical and preclinical studies that utilize different nanoformulations in veterinary oncology, as well as the application of nanoparticles for cancer diagnosis and imaging. The toxicology of various nanoformulations is also considered. Given the benefits of nanoformulations demonstrated in human medicine, nanoformulated drugs are likely to gain more traction in veterinary oncology. Published by Elsevier Ltd.

  15. Veterinary clinical pathologists in the biopharmaceutical industry.

    Science.gov (United States)

    Schultze, A Eric; Bounous, Denise I; Bolliger, Anne Provencher

    2008-06-01

    There is an international shortage of veterinary clinical pathologists in the workplace. Current trainees in veterinary clinical pathology may choose to pursue careers in academe, diagnostic laboratories, government health services, biopharmaceutical companies, or private practice. Academic training programs attempt to provide trainees with an exposure to several career choices. However, due to the proprietary nature of much of the work in the biopharmaceutical industry, trainees may not be fully informed regarding the nature of work for veterinary clinical pathologists and the myriad opportunities that await employment in the biopharmaceutical industry. The goals of this report are to provide trainees in veterinary clinical pathology and other laboratory personnel with an overview of the work-life of veterinary clinical pathologists employed in the biopharmaceutical industry, and to raise the profile of this career choice for those seeking to enter the workforce. Biographical sketches, job descriptions, and motivation for 3 successful veterinary clinical pathologists employed in the biopharmaceutical industry are provided. Current and past statistics for veterinary clinical pathologists employed in the biopharmaceutical industry are reviewed. An overview of the drug development process and involvement of veterinary clinical pathologists in the areas of discovery, lead optimization, and candidate evaluation are discussed. Additional duties for veterinary clinical pathologists employed in the biopharmaceutical industry include development of biomarkers and new technologies, service as scientific resources, diagnostic support services, and laboratory management responsibilities. There are numerous opportunities available for trainees in veterinary clinical pathology to pursue employment in the biopharmaceutical industry and enjoy challenging and rewarding careers.

  16. Bioequivalence study of two formulations of candesartan cilexetil tablet in healthy subjects under fasting conditions

    Directory of Open Access Journals (Sweden)

    Tjandrawinata RR

    2013-08-01

    Full Text Available Raymond R Tjandrawinata,1 Effi Setiawati,2 Danang Agung Yunaidi,2 Ronal Simanjuntak,2 Iwan Dwi Santoso,2 Liana W Susanto1 1Dexa Laboratories of Biomolecular Sciences (DLBS, Cikarang, Indonesia; 2Bioavailability and Bioequivalence Laboratory, PT Equilab International, Jakarta, Indonesia Introduction: The present study was conducted to compare the bioavailability of two candesartan cilexetil 16 mg tablet formulations (test and reference formulations. Materials and methods: This study was a randomized, single- blind, two-period, cross-over study which included 24 healthy adult male and female subjects under fasting conditions. The pharmacokinetic parameters were determined based on the concentrations of candesartan (CAS 139481-59-7, using ultra-pressure high-performance liquid chromatography with a tandem mass spectrometer detector. In each of the two study periods (separated by a washout period of 1 week, a single dose of test or reference product was administered. The pharmacokinetic parameters assessed were area under the plasma concentration time curve (AUC from time 0 hours to 24 hours, AUC from time zero to infinity, the peak plasma concentration of the drug (Cmax, time to achieve the Cmax, and the elimination half-life. Results: The geometric mean ratios (90% confidence interval of the test drug/reference drug for candesartan were 100.92% (92.15%–110.52% for the AUC from 0 hours to 24 hours, 100.24% (92.24%–108.95% for the AUC from time zero to infinity, and 106.71% (93.20%–122.18% for the Cmax. The differences between the test and reference product in the time to achieve Cmax values and elimination half-life values were not statistically significant (P > 0.05. The 90% confidence intervals of the test/reference AUC ratio and Cmax ratio of candesartan were within the acceptance range for bioequivalence. There was no adverse event encountered during this bioequivalence study. Conclusion: It was concluded that the two candesartan tablet

  17. Pharmacokinetics and bioequivalence testing of generic fluconazole preparations in healthy thai volunteers.

    Science.gov (United States)

    Manorot, M; Rojanasthien, N; Kumsorn, B; Teekachunhatean, S

    2000-07-01

    To determine the bioequivalence of two oral formulations of generic fluconazole in twelve healthy Thai volunteers. The test preparation was Flucozole (Siam Bheasach, Thailand) and the reference was Diflucan (Pfizer Inc.). The two products were administered as 200 mg single oral doses in a two-period crossover design with a two-week washout period. After drug administration, serial blood samples were collected over a period of 72 hours. Serum fluconazole concentrations were determined by HPLC, and the pharmacokinetic parameters were analyzed by non-compartmental analysis. The time to reach the maximal concentration (Tmax, hour) of Flucozole (1.18 +/- 0.56) was statistically faster than that of Diflulan (1.59 +/- 0.54). The 90% confidence intervals of the AUC(0 - infinity) ratio and the Cmax, ratio muT/muR for Flucozole/Diflucan were 0.97 - 1.20 and 1.01 - 1.26, respectively. These values were within the acceptable bioequivalence intervals of 0.80 - 1.25 and 0.7 - 1.43 for the ratio of the average AUC(0 - infinity) and Cmax, respectively. Thus, our study demonstrated the bioequivalence of Flucozole and Diflucan with respect to the rate (Cmax) and extent of absorption (AUC(0 - infinity).

  18. Pharmacokinetics and bioequivalence testing of five commercial formulations of omeprazole in the horse.

    Science.gov (United States)

    Sykes, B W; Underwood, C; Greer, R; McGowan, C M; Mills, P C

    2016-02-01

    Omeprazole is widely used in the treatment of equine gastric ulcer syndrome. To date, little is known about the relative pharmacokinetics of the different formulations making comparisons between products difficult. The objectives of the study were to investigate the relative pharmacokinetics of five commercially available formulations of omeprazole in the horse and to test for bioequivalence of four of the formulations using one of the formulations as a reference standard. Twelve mature Thoroughbred horses were fasted for 16 h then administered 2 g of each formulation in a cross-over design. Serial blood samples were collected and plasma omeprazole concentration was determined by ultra high-performance liquid chromatography-mass spectrometry (UHPLC-MS). No significant differences were present between three of the formulations and the reference formulation, while the fourth formulation had a lower Cmax and longer Tmax than the reference formulation. Bioequivalence against the reference formulation could not be demonstrated for any of the formulations tested. The findings of the study suggested that the method of protection utilised by different formulations of omeprazole (enteric-coated granules vs. buffering) does not significantly alter the pharmacokinetics of the drug. Further work to establish bioequivalence is needed before direct comparisons can be drawn between different formulations. © 2015 John Wiley & Sons Ltd.

  19. Bioequivalence between innovator and generic tacrolimus in liver and kidney transplant recipients: A randomized, crossover clinical trial.

    Directory of Open Access Journals (Sweden)

    Rita R Alloway

    2017-11-01

    Full Text Available Although the generic drug approval process has a long-term successful track record, concerns remain for approval of narrow therapeutic index generic immunosuppressants, such as tacrolimus, in transplant recipients. Several professional transplant societies and publications have generated skepticism of the generic approval process. Three major areas of concern are that the pharmacokinetic properties of generic products and the innovator (that is, "brand" product in healthy volunteers may not reflect those in transplant recipients, bioequivalence between generic and innovator may not ensure bioequivalence between generics, and high-risk patients may have specific bioequivalence concerns. Such concerns have been fueled by anecdotal observations and retrospective and uncontrolled published studies, while well-designed, controlled prospective studies testing the validity of the regulatory bioequivalence testing approach for narrow therapeutic index immunosuppressants in transplant recipients have been lacking. Thus, the present study prospectively assesses bioequivalence between innovator tacrolimus and 2 generics in individuals with a kidney or liver transplant.From December 2013 through October 2014, a prospective, replicate dosing, partially blinded, randomized, 3-treatment, 6-period crossover bioequivalence study was conducted at the University of Cincinnati in individuals with a kidney (n = 35 or liver transplant (n = 36. Abbreviated New Drug Applications (ANDA data that included manufacturing and healthy individual pharmacokinetic data for all generics were evaluated to select the 2 most disparate generics from innovator, and these were named Generic Hi and Generic Lo. During the 8-week study period, pharmacokinetic studies assessed the bioequivalence of Generic Hi and Generic Lo with the Innovator tacrolimus and with each other. Bioequivalence of the major tacrolimus metabolite was also assessed. All products fell within the US Food and Drug

  20. Bioequivalence between innovator and generic tacrolimus in liver and kidney transplant recipients: A randomized, crossover clinical trial.

    Science.gov (United States)

    Alloway, Rita R; Vinks, Alexander A; Fukuda, Tsuyoshi; Mizuno, Tomoyuki; King, Eileen C; Zou, Yuanshu; Jiang, Wenlei; Woodle, E Steve; Tremblay, Simon; Klawitter, Jelena; Klawitter, Jost; Christians, Uwe

    2017-11-01

    Although the generic drug approval process has a long-term successful track record, concerns remain for approval of narrow therapeutic index generic immunosuppressants, such as tacrolimus, in transplant recipients. Several professional transplant societies and publications have generated skepticism of the generic approval process. Three major areas of concern are that the pharmacokinetic properties of generic products and the innovator (that is, "brand") product in healthy volunteers may not reflect those in transplant recipients, bioequivalence between generic and innovator may not ensure bioequivalence between generics, and high-risk patients may have specific bioequivalence concerns. Such concerns have been fueled by anecdotal observations and retrospective and uncontrolled published studies, while well-designed, controlled prospective studies testing the validity of the regulatory bioequivalence testing approach for narrow therapeutic index immunosuppressants in transplant recipients have been lacking. Thus, the present study prospectively assesses bioequivalence between innovator tacrolimus and 2 generics in individuals with a kidney or liver transplant. From December 2013 through October 2014, a prospective, replicate dosing, partially blinded, randomized, 3-treatment, 6-period crossover bioequivalence study was conducted at the University of Cincinnati in individuals with a kidney (n = 35) or liver transplant (n = 36). Abbreviated New Drug Applications (ANDA) data that included manufacturing and healthy individual pharmacokinetic data for all generics were evaluated to select the 2 most disparate generics from innovator, and these were named Generic Hi and Generic Lo. During the 8-week study period, pharmacokinetic studies assessed the bioequivalence of Generic Hi and Generic Lo with the Innovator tacrolimus and with each other. Bioequivalence of the major tacrolimus metabolite was also assessed. All products fell within the US Food and Drug Administration

  1. A bioequivalence study of two memantine formulations in healthy Chinese male volunteers
.

    Science.gov (United States)

    Deng, Ying; Zhuang, Jialang; Wu, Jingguo; Chen, Jiangying; Ding, Liang; Wang, Xueding; Huang, Lihui; Zeng, Guixiong; Chen, Jie; Ma, Zhongfu; Chen, Xiao; Zhong, Guoping; Huang, Min; Zhao, Xianglan

    2017-10-01

    The aim of the current study is to evaluate the bioequivalence between the test and reference formulations of memantine in a single-dose, two-period and two-sequence crossover study with a 44-day washout interval. A total of 20 healthy Chinese male volunteers were enrolled and completed the study, after oral administration of single doses of 10 mg test and reference formulations of memantine. The blood samples were collected at different time points and memantine concentrations were determined by a fully validated HPLC-MS/MS method. The evaluated pharmacokinetic parameters (test vs. reference) including Cmax (18 ± 3.2 vs. 17.8 ± 3.4), AUC0-t (1,188.5 ± 222.2 vs. 1,170.9 ± 135.7), and AUC0-∞ (1,353.3 ± 258.6 vs. 1,291.3 ± 136.7) values were assessed for bioequivalence based on current guidelines. The observed pharmacokinetic parameters of memantine test drug were similar to those of the reference formulation. The 90% confidence intervals of test/reference ratios for Cmax, AUC0-t, and AUC0-∞ were within the bioequivalence acceptance range of 80 - 125%. The results obtained from the healthy Chinese subjects in this study suggests that the test formulation of memantine 10 mg tablet is bioequivalent to the reference formulation (Ebixa®10 mg tablet).
.

  2. Holistic pediatric veterinary medicine.

    Science.gov (United States)

    Pesch, Lisa

    2014-03-01

    Holistic veterinary medicine treats the whole patient including all physical and behavioral signs. The root cause of disease is treated at the same time as accompanying clinical signs. Herbal and nutritional supplements can help support tissue healing and proper organ functioning, thereby reducing the tendency of disease progression over time. Proper selection of homeopathic remedies is based on detailed evaluation of clinical signs. Herbal medicines are selected based on organ(s) affected and the physiologic nature of the imbalance. Many herbal and nutraceutical companies provide support for veterinarians, assisting with proper formula selection, dosing, drug interactions, and contraindications. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Assessment of veterinary services in central Ethiopia: A case study ...

    African Journals Online (AJOL)

    2003; Halderman, 2005). Animals provide highly nutritious foods, and provide. Ethiop. Vet. .... providing veterinary services in the. District include veterinary drugs shops and mobile clinics providing full time ... 4) The public veterinary service was chosen as first choice for effectiveness and costliness compared to private ...

  4. 75 FR 4576 - Veterinary Medicine Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2010-01-28

    ... HUMAN SERVICES Food and Drug Administration Veterinary Medicine Advisory Committee; Notice of Meeting... the public. Name of Committee: Veterinary Medicine Advisory Committee. General Function of the... PROHEART 6 (NADA 141-189), the subsequent safety data collected under the Center for Veterinary Medicine's...

  5. 75 FR 36588 - Veterinary Feed Directive; Extension of Comment Period

    Science.gov (United States)

    2010-06-28

    ... HUMAN SERVICES Food and Drug Administration 21 CFR Parts 510, 514, and 558 Veterinary Feed Directive... need for improvements to the veterinary feed directive (VFD) regulation. The agency is taking this..., rm. 1061, Rockville, MD 20852. FOR FURTHER INFORMATION CONTACT: Neal Bataller, Center for Veterinary...

  6. Development of a simple multi-residue determination method of 80 veterinary drugs in Oplegnathus punctatus by liquid chromatography coupled to quadrupole Orbitrap mass spectrometry.

    Science.gov (United States)

    Zhao, Fei; Gao, Xin; Tang, Zhixu; Luo, Xin; Wu, Miaomiao; Xu, Jiachao; Fu, Xiaoting

    2017-10-15

    A simple, rapid and sensitive multi-residue analytical method was developed and validated for 80 veterinary drugs in Oplegnathus punctatus using ultrahigh performance liquid chromatography-Orbitrap high resolution mass spectrometry (LC-HRMS). The analytes belong to 12 different families include benzimidazoles, β-lactams, lincosamides, macrolides, nitromidazoles, quinolones, sulfonamides and trimethoprim, tetracyclines, triphenylmethane dyes, amphenicols, nonsteroidal estrogens and steroid hormones. The sample preparation was optimized base on QuEChERS (quick, easy, cheap, effective, rugged and safe) procedure. A very simple and sufficient preparation procedure without salting-out and complex clean-up process was studied. It had been proved that water in the extract was helpful for extracting hydrophilic compounds and precipitating the lipids during the subsequent cleaning process. In addition, an appropriate percent of methanol was necessary to some analytes. Finally, a mixture of acetonitrile, methanol and water (3:1:1, v/v/v) which include 1% acetic acid and 10mM ethylenediaminetetraacetic acid disodium salt 2-hydrate was selected as the extraction solvent, and the clean-up step consisted of a low temperature procedure and two times of high-speed centrifugation to deproteinize and remove lipids. The detection and quantification of all compounds were performed by ultrahigh performance liquid chromatography coupled with electrospray ionization quadrupole Orbitrap high resolution mass spectrometry in positive and negative ion mode. This methodology was validated according to the Commission Decision 2002/657/EC and SANTE/11945/2015. The recoveries ranged from 60.74%-109.85% with relative standard deviations (RSDs)<20%. The limits of quantification (LOQs) were 0.25-25ug/kg, for the analytes which the MRL or MRPL had been established in fish tissue, the LOQs were all lower than their own legal tolerances. The values of decision limit (CCα) and detection capability

  7. NIGERIAN VETERINARY JOURNAL

    African Journals Online (AJOL)

    ADEYEYE

    Nigerian Veterinary Journal 37(3). 2016. Okorie-Kanu et al. 160. NIGERIAN VETERINARY JOURNAL. ISSN 0331-3026. Nig. Vet. J., September 2016. Vol. 37 (3): ... Nigeria; 3Department of Veterinary Pathology and Microbiology, University of Nigeria, Nsukka, Enugu state,. Nigeria. ...... (ASVCP), International Veterinary.

  8. NIGERIAN VETERINARY JOURNAL

    African Journals Online (AJOL)

    ADEYEYE

    1Department of Veterinary Anatomy, Faculty of Veterinary Medicine, University of Ibadan, Nigeria.. 2Department of Veterinary Anatomy, College of Veterinary Medicine, Federal University of Abeokuta, Ogun State,. Nigeria. *Corresponding Authors: .... medial and lateral canthi of each eye. Philtrum Height (PH). Measured ...

  9. NIGERIAN VETERINARY JOURNAL

    African Journals Online (AJOL)

    ADEYEYE

    2000-07-02

    Jul 2, 2000 ... Nigerian Veterinary Journal 36(4). 2015. Owoyemi et al. 1341. NIGERIAN VETERINARY JOURNAL. ISSN 0331-3026. Nig. Vet. J., December 2015 ... medicine, 3Department of Veterinary Anatomy, Faculty of Veterinary Medicine, University of Ibadan, Nigeria. .... in wound or burn healing, internal intake of.

  10. Assessment of Veterinary Pharmaceutical Products Registered in ...

    African Journals Online (AJOL)

    Topically administered dosage forms included solutions, sprays, ointments, creams, shampoos and powders, while those delivered via the intrauterine route included pessaries, solutions and suspensions. Keywords: dosage forms, administration route, veterinary pharmaceutical products, animal species, drug delivery.

  11. 75 FR 29352 - Draft Guidance for Industry on Data Elements for Submission of Veterinary Adverse Event Reports...

    Science.gov (United States)

    2010-05-25

    ... of Veterinary Adverse Event Reports to the Center for Veterinary Medicine; Availability AGENCY: Food... Veterinary Adverse Event Reports to the Center for Veterinary Medicine.'' The purpose of this draft guidance is to assist sponsors or non-applicants with filling out form FDA 1932, ``Veterinary Adverse Drug...

  12. Bioequivalence study of two formulations of bisoprolol fumarate film-coated tablets in healthy subjects

    Science.gov (United States)

    Tjandrawinata, Raymond R; Setiawati, Effi; Yunaidi, Danang Agung; Santoso, Iwan Dwi; Setiawati, Arini; Susanto, Liana W

    2012-01-01

    Background The present study was conducted to compare the bioavailability of two bisoprolol fumarate 5 mg film-coated tablet formulations (test and reference formulations). Patients and methods This study was a randomized, single-blind, two-period, two-sequence crossover study that included 18 healthy adult male and female subjects under fasting condition. The pharmacokinetic parameters were determined based on the concentrations of bisoprolol (CAS 66722-44-9), using ultraperformance liquid chromatography with a tandem mass spectrometer detector. In each of the two study periods (separated by a washout of 1 week) a single dose of test or reference product was administered. The pharmacokinetic parameters assessed were area under the plasma concentration-time curve from time zero to 48 hours (AUCt), AUC from time zero to infinity (AUCinf), the peak plasma concentration of the drug (Cmax), time needed to achieve Cmax (tmax), and the elimination half-life (t½). Results The geometric mean ratios (90% confidence intervals) of the test drug/reference drug for bisoprolol were 101.61% (96.14%–107.38%) for AUCt, 101.31% (95.66%–107.29%) for AUCinf, and 100.28% (93.90%–107.09%) for Cmax. The differences between the test and reference drug products for bisoprolol tmax and t½ values were not statistically significant (P > 0.05). There was no adverse event encountered during this bioequivalence test. The 90% confidence intervals of the test/reference AUC ratio and Cmax ratio of bisoprolol were within the acceptance range for bioequivalence. Conclusion It was concluded that the two bisoprolol film-coated tablet formulations (the test and reference products) were bioequivalent in terms of the rate and extent of absorption. PMID:23139624

  13. Information technology in veterinary pharmacology instruction.

    Science.gov (United States)

    Kochevar, Deborah T

    2003-01-01

    Veterinary clinical pharmacology encompasses all interactions between drugs and animals and applies basic and clinical knowledge to improve rational drug use and patient outcomes. Veterinary pharmacology instructors set educational goals and objectives that, when mastered by students, lead to improved animal health. The special needs of pharmacology instruction include establishing a functional interface between basic and clinical knowledge, managing a large quantity of information, and mastering quantitative skills essential to successful drug administration and analysis of drug action. In the present study, a survey was conducted to determine the extent to which veterinary pharmacology instructors utilize information technology (IT) in their teaching. Several IT categories were investigated, including Web-based instructional aids, stand-alone pharmacology software, interactive videoconferencing, databases, personal digital assistants (PDAs), and e-book applications. Currently IT plays a largely ancillary role in pharmacology instruction. IT use is being expanded primarily through the efforts of two veterinary professional pharmacology groups, the American College of Veterinary Clinical Pharmacology (ACVCP) and the American Academy of Veterinary Pharmacology and Therapeutics (AAVPT). The long-term outcome of improved IT use in pharmacology instruction should be to support the larger educational mission of active learning and problem solving. Creation of high-quality IT resources that promote this goal has the potential to improve veterinary pharmacology instruction within and across institutions.

  14. Investigation of the role of environmental contamination in the occurrence of residues of the veterinary drug phenylbutazone in cattle.

    Science.gov (United States)

    Barnes, Paul; Fodey, Terence L; Smyth, Wesley G; Crooks, Steven R H

    2017-04-01

    Phenylbutazone is a non-steroidal anti-inflammatory drug licensed for use in horses to treat musculoskeletal disorders. It is not permitted in the European Union for use in animals destined for the food chain. Official statistics provided by the European Food Safety Authority (EFSA) show that 0.18% of bovines tested in the European Union between 2008 and 2014 for non-steroidal anti-inflammatory drugs were non-compliant, with phenylbutazone representing over 28% of these. Anecdotal evidence suggests animals that have not been treated with the drug may have produced non-compliant samples, possibly through some form of contamination. In this study, ultra-high-performance liquid chromatography coupled with mass-spectrometric detection was applied to bovine plasma samples to determine if detectable residues (CCα = 0.28 ng ml-1) may occur in untreated animals as a result of environmental contamination through normal farming practice. The study demonstrates that waste from animals treated with phenylbutazone, and spread on an area of pasture, can contaminate untreated bovines grazing the pasture many weeks later. It was determined that this contamination, which can persist over a significant period, may be due to the ingestion of as little as 30 μg phenylbutazone by a 500 kg bullock.

  15. Matrix-effect free multi-residue analysis of veterinary drugs in food samples of animal origin by nanoflow liquid chromatography high resolution mass spectrometry.

    Science.gov (United States)

    Alcántara-Durán, Jaime; Moreno-González, David; Gilbert-López, Bienvenida; Molina-Díaz, Antonio; García-Reyes, Juan F

    2018-04-15

    In this work, a sensitive method based on nanoflow liquid chromatography high-resolution mass spectrometry has been developed for the multiresidue determination of veterinary drugs residues in honey, veal muscle, egg and milk. Salting-out supported liquid extraction was employed as sample treatment for milk, veal muscle and egg, while a modified QuEChERS procedure was used in honey. The enhancement of sensitivity provided by the nanoflow LC system also allowed the implementation of high dilution factors as high as 100:1. For all matrices tested, matrix effects were negligible starting from a dilution factor of 100, enabling, thus, the use of external standard calibration instead of matrix-matched calibration of each sample, and the subsequent increase of laboratory throughput. At spiked levels as low as 0.1 or 1 µg kg-1 before the 1:100 dilution, the obtained signals were still significantly higher than the instrumental limit of quantitation (S/N 10). Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Analysis of veterinary drug and pesticide residues in animal feed by high-resolution mass spectrometry: comparison between time-of-flight and Orbitrap.

    Science.gov (United States)

    Gómez-Pérez, María Luz; Romero-González, Roberto; Martínez Vidal, José Luis; Garrido Frenich, Antonia

    2015-01-01

    The use of medium-high-resolution mass spectrometers (M-HRMS) provides many advantages in multi-residue analysis. A comparison between two mass spectrometers, medium-resolution (MRMS) time-of-flight (TOF) and high-resolution (HRMS) Orbitrap, has been carried out for the analysis of toxic compounds in animal feed. More than 300 compounds belonging to several classes of veterinary drugs (VDs) and pesticides have been determined in different animal feed samples using a generic extraction method. The use of a clean-up procedure has been evaluated in both instruments, and several validation parameters have been established, such as the matrix effect, linearity, recovery and sensitivity. Finally, both instruments have been used during the analysis of 18 different feed samples (including chicken, hen, rabbit and horse). Some VDs (sulfadiazine, trimethoprim, robenidine and monensin sodium) and one pesticide (chlorpyrifos) have been identified. In general, better results were obtained using the Orbitrap, such as sensitivity (1-12.5 µg kg(-1)) and recovery values (60-125%). Moreover, this analyser had several software tools, which reduced the time for data processing and were easy to use, performing quick screening for more than 450 compounds in less than 5 min. However, some disadvantages such as the high cost and a decrease in the number of detected compounds at low concentrations must be taken into account.

  17. The future of veterinary parasitology.

    Science.gov (United States)

    Coles, G C

    2001-07-12

    Current evidence suggests research in veterinary parasitology is in decline despite its importance. This is particularly true in the UK where research funds have been diverted into BSE. Decline in interest in veterinary parasitology is at least in part due to the success of major pharmaceutical companies in producing a range of effective and safe anti-parasitic drugs. Research is needed because of the effects of parasites on animal welfare and the economic costs of parasites. However, there is little information on the actual costs of animal parasites. Another major reason for research is the development of drug resistance in protozoa, helminths and arthropods of veterinary importance. This is a serious problem particularly for sheep and goats in the southern hemisphere. A prioritised list of research requirements is suggested: (i) new drugs; (ii) resistance management; (iii) vaccines; (iv) breeding for resistance; (v) improved diagnostics; (vi) zoonoses; (vii) global warming and parasites. There is a major political challenge to raise the profile of veterinary parasitology and thus the funding essential for its advancement and the continued welfare and productivity of animals.

  18. Authorization and Toxicity of Veterinary Drugs and Plant Protection Products: Residues of the Active Ingredients in Food and Feed and Toxicity Problems Related to Adjuvants

    Directory of Open Access Journals (Sweden)

    Szandra Klátyik

    2017-09-01

    Full Text Available Chemical substances applied in animal husbandry or veterinary medicine and in crop protection represent substantial environmental loads, and their residues occur in food and feed products. Product approval is governed differently in these two sectors in the European Union (EU, and the occurrence of veterinary drug (VD and pesticide residues indicated by contamination notification cases in the Rapid Alert System for Food and Feed of the EU also show characteristic differences. While the initial high numbers of VD residues reported in 2002 were successfully suppressed to less than 100 cases annually by 2006 and on, the number of notification cases for pesticide residues showed a gradual increase from a low (approximately 50 cases annually initial level until 2005 to more than 250 cases annually after 2009, with a halt occurring only in 2016. Main notifiers of VD residues include Germany, Belgium, the UK, and Italy (63, 59, 42, and 31 notifications announced, respectively, and main consigning countries of non-compliances are Vietnam, India, China, and Brazil (88, 50, 34, and 23 notifications, respectively. Thus, countries of South and Southeast Asia are considered a vulnerable point with regard to VD residues entering the EU market. Unintended side effects of VDs and plant protection products may be caused not only by the active ingredients but also by various additives in these preparations. Adjuvants (e.g., surfactants and other co-formulants used in therapeutic agents and feed additives, as well as in pesticide formulations have long been considered as inactive ingredients in the aspects of the required main biological effect of the pharmaceutical or pesticide, and in turn, legal regulations of the approval and marketing of these additives specified significantly less stringent risk assessment requirements, than those specified for the active ingredients. However, numerous studies have shown additive, synergistic, or antagonistic side effects

  19. Authorization and Toxicity of Veterinary Drugs and Plant Protection Products: Residues of the Active Ingredients in Food and Feed and Toxicity Problems Related to Adjuvants.

    Science.gov (United States)

    Klátyik, Szandra; Bohus, Péter; Darvas, Béla; Székács, András

    2017-01-01

    Chemical substances applied in animal husbandry or veterinary medicine and in crop protection represent substantial environmental loads, and their residues occur in food and feed products. Product approval is governed differently in these two sectors in the European Union (EU), and the occurrence of veterinary drug (VD) and pesticide residues indicated by contamination notification cases in the Rapid Alert System for Food and Feed of the EU also show characteristic differences. While the initial high numbers of VD residues reported in 2002 were successfully suppressed to less than 100 cases annually by 2006 and on, the number of notification cases for pesticide residues showed a gradual increase from a low (approximately 50 cases annually) initial level until 2005 to more than 250 cases annually after 2009, with a halt occurring only in 2016. Main notifiers of VD residues include Germany, Belgium, the UK, and Italy (63, 59, 42, and 31 notifications announced, respectively), and main consigning countries of non-compliances are Vietnam, India, China, and Brazil (88, 50, 34, and 23 notifications, respectively). Thus, countries of South and Southeast Asia are considered a vulnerable point with regard to VD residues entering the EU market. Unintended side effects of VDs and plant protection products may be caused not only by the active ingredients but also by various additives in these preparations. Adjuvants (e.g., surfactants) and other co-formulants used in therapeutic agents and feed additives, as well as in pesticide formulations have long been considered as inactive ingredients in the aspects of the required main biological effect of the pharmaceutical or pesticide, and in turn, legal regulations of the approval and marketing of these additives specified significantly less stringent risk assessment requirements, than those specified for the active ingredients. However, numerous studies have shown additive, synergistic, or antagonistic side effects between the

  20. Authorization and Toxicity of Veterinary Drugs and Plant Protection Products: Residues of the Active Ingredients in Food and Feed and Toxicity Problems Related to Adjuvants

    Science.gov (United States)

    Klátyik, Szandra; Bohus, Péter; Darvas, Béla; Székács, András

    2017-01-01

    Chemical substances applied in animal husbandry or veterinary medicine and in crop protection represent substantial environmental loads, and their residues occur in food and feed products. Product approval is governed differently in these two sectors in the European Union (EU), and the occurrence of veterinary drug (VD) and pesticide residues indicated by contamination notification cases in the Rapid Alert System for Food and Feed of the EU also show characteristic differences. While the initial high numbers of VD residues reported in 2002 were successfully suppressed to less than 100 cases annually by 2006 and on, the number of notification cases for pesticide residues showed a gradual increase from a low (approximately 50 cases annually) initial level until 2005 to more than 250 cases annually after 2009, with a halt occurring only in 2016. Main notifiers of VD residues include Germany, Belgium, the UK, and Italy (63, 59, 42, and 31 notifications announced, respectively), and main consigning countries of non-compliances are Vietnam, India, China, and Brazil (88, 50, 34, and 23 notifications, respectively). Thus, countries of South and Southeast Asia are considered a vulnerable point with regard to VD residues entering the EU market. Unintended side effects of VDs and plant protection products may be caused not only by the active ingredients but also by various additives in these preparations. Adjuvants (e.g., surfactants) and other co-formulants used in therapeutic agents and feed additives, as well as in pesticide formulations have long been considered as inactive ingredients in the aspects of the required main biological effect of the pharmaceutical or pesticide, and in turn, legal regulations of the approval and marketing of these additives specified significantly less stringent risk assessment requirements, than those specified for the active ingredients. However, numerous studies have shown additive, synergistic, or antagonistic side effects between the

  1. Needle-free subcutaneous sumatriptan (Sumavel DosePro): bioequivalence and ease of use.

    Science.gov (United States)

    Brandes, Jan Lewis; Cady, Roger K; Freitag, Fred G; Smith, Timothy R; Chandler, Patricia; Fox, Anthony W; Linn, Lawrence; Farr, Stephen J

    2009-01-01

    presentation of s.c. sumatriptan that delivers drug effectively, is bioequivalent to the existing needle auto-injector when used at the thigh or abdomen, and is easy to use.

  2. Bioequivalence of 0.1% mometasone furoate lotion to 0.1% mometasone furoate hydrogel.

    Science.gov (United States)

    Greive, Kerryn A; Barnes, Tanya M

    2016-05-01

    Vehicles used for topical therapy can affect drug delivery and patient adherence. This study compared the bioequivalence of 0.1% mometasone furoate lotion (reference) and 0.1% mometasone furoate hydrogel (test). Moisturising capacity and sensitivity/irritancy potential were also determined. Bioequivalence was assessed by vasoconstriction assay and analysis of area under the effect curve (AUEC0-24 ) according to the Food and Drug Administration (FDA) guidance. In total, 131 individuals were screened in a pilot dose duration-response study, and 90 responders enrolled. For the pivotal study, lotion and hydrogel (5 mg/cm(2) ) were applied in a double-blind manner. Vasoconstriction was evaluated by chromameter at 0, 2, 4, 6, 19 and 24 h following lotion and hydrogel removal. Barrier function was measured by assessment of transepidermal water loss (TEWL) and skin hydration. Sensitivity/irritancy potential was assessed by repeat insult patch tests. The mean AUEC0-24 of the test hydrogel and reference lotion were -18.200 and -18.953, respectively, with test/reference = 96%, with 90% confidence interval (0.81, 1.12), which was within FDA guidance limits. TEWL was found to significantly decrease by 43 and 29% after 2 and 24 h, respectively, while skin hydration significantly increased by 38% after 24 h following a single application of hydrogel. The hydrogel was also found to be non-irritating and non-sensitising. No adverse events were observed. Mometasone furoate hydrogel is bioequivalent to mometasone furoate lotion. This novel hydrogel formulation provides effective drug delivery, increases moisturisation and affords greater ease and tolerability of application, improving patients' adherence to therapy. © 2014 The Authors. Australasian Journal of Dermatology published by Wiley Publishing Asia Pty Ltd on behalf of The Australasian College of Dermatologists.

  3. Bioequivalence study of two formulations of candesartan cilexetil tablet in healthy subjects under fasting conditions

    Science.gov (United States)

    Tjandrawinata, Raymond R; Setiawati, Effi; Yunaidi, Danang Agung; Simanjuntak, Ronal; Santoso, Iwan Dwi; Susanto, Liana W

    2013-01-01

    Introduction The present study was conducted to compare the bioavailability of two candesartan cilexetil 16 mg tablet formulations (test and reference formulations). Materials and methods This study was a randomized, single- blind, two-period, cross-over study which included 24 healthy adult male and female subjects under fasting conditions. The pharmacokinetic parameters were determined based on the concentrations of candesartan (CAS 139481-59-7), using ultra-pressure high-performance liquid chromatography with a tandem mass spectrometer detector. In each of the two study periods (separated by a washout period of 1 week), a single dose of test or reference product was administered. The pharmacokinetic parameters assessed were area under the plasma concentration time curve (AUC) from time 0 hours to 24 hours, AUC from time zero to infinity, the peak plasma concentration of the drug (Cmax), time to achieve the Cmax, and the elimination half-life. Results The geometric mean ratios (90% confidence interval) of the test drug/reference drug for candesartan were 100.92% (92.15%–110.52%) for the AUC from 0 hours to 24 hours, 100.24% (92.24%–108.95%) for the AUC from time zero to infinity, and 106.71% (93.20%–122.18%) for the Cmax. The differences between the test and reference product in the time to achieve Cmax values and elimination half-life values were not statistically significant (P > 0.05). The 90% confidence intervals of the test/reference AUC ratio and Cmax ratio of candesartan were within the acceptance range for bioequivalence. There was no adverse event encountered during this bioequivalence study. Conclusion It was concluded that the two candesartan tablet formulations (the test and reference product) were bioequivalent. PMID:23990709

  4. Bioequivalence study of two formulations of candesartan cilexetil tablet in healthy subjects under fasting conditions.

    Science.gov (United States)

    Tjandrawinata, Raymond R; Setiawati, Effi; Yunaidi, Danang Agung; Simanjuntak, Ronal; Santoso, Iwan Dwi; Susanto, Liana W

    2013-01-01

    The present study was conducted to compare the bioavailability of two candesartan cilexetil 16 mg tablet formulations (test and reference formulations). This study was a randomized, single- blind, two-period, cross-over study which included 24 healthy adult male and female subjects under fasting conditions. The pharmacokinetic parameters were determined based on the concentrations of candesartan (CAS 139481-59-7), using ultra-pressure high-performance liquid chromatography with a tandem mass spectrometer detector. In each of the two study periods (separated by a washout period of 1 week), a single dose of test or reference product was administered. The pharmacokinetic parameters assessed were area under the plasma concentration time curve (AUC) from time 0 hours to 24 hours, AUC from time zero to infinity, the peak plasma concentration of the drug (Cmax), time to achieve the Cmax, and the elimination half-life. The geometric mean ratios (90% confidence interval) of the test drug/reference drug for candesartan were 100.92% (92.15%-110.52%) for the AUC from 0 hours to 24 hours, 100.24% (92.24%-108.95%) for the AUC from time zero to infinity, and 106.71% (93.20%-122.18%) for the Cmax. The differences between the test and reference product in the time to achieve Cmax values and elimination half-life values were not statistically significant (P > 0.05). The 90% confidence intervals of the test/reference AUC ratio and Cmax ratio of candesartan were within the acceptance range for bioequivalence. There was no adverse event encountered during this bioequivalence study. It was concluded that the two candesartan tablet formulations (the test and reference product) were bioequivalent.

  5. Bioequivalence study of two fluconazole capsule formulations in healthy volunteers.

    Science.gov (United States)

    Pereira, R; Fidelis, S; Vanunci, M L P; Oliveira, C H; Mendes, G D; Abib, E; Moreno, R A

    2004-01-01

    To compare the bioavailability of a fluconazole 150 mg capsule formulation from Laboratório Teuto Brasileiro Ltd., Brazil (test formulation), and Zoltec 150 mg capsule from Laboratórios Pfizer Ltd., Brazil (reference formulation), in 24 volunteers of both sexes. The study was conducted open with randomized 2-period crossover design and a 2-week washout period. Plasma samples were obtained over a 168-hour interval. Fluconazole concentrations were analyzed by combined reversed-phase liquid chromatography and tandem mass spectrometry (LC/MS/MS) with positive ion electrospray ionization using selected ion monitoring method. From the fluconazole plasma concentration vs. time curves the following pharmacokinetic parameters were obtained: AUC(last), AUC(0-inf) and C(max). Geometric mean of fluconazole/Zoltec 150 mg individual percent ratio was 102.6% for AUC(last), 102.2% for AUC(0-inf) and 109.4% for C(max). The 90% confidence intervals were 97.3-108.2%, 97.0-107.8%, and 103.1-116.0%, respectively. Since the 90% CI for both Cmax, AUC(last) and AUC(0-inf) were within the 80-125% interval proposed by the Food and Drug Administration, it was concluded that fluconazole 150 mg capsule was bioequivalent to Zoltec 150 mg, according to both the rate and extent of absorption.

  6. Bioequivalence testing of a new tablet formulation of generic fluoxetine.

    Science.gov (United States)

    Jovanović, D; Kilibarda, V; Dordević, S; Jovanović, M; Jovic-Stosić, J; Srdić, D; Knezević, T

    2006-01-01

    The pharmacokinetics and relative bioavailability of fluoxetine capsules (reference) and tablets (test) were compared in 24 healthy subjects of both sexes after a single 20 mg oral dose of fluoxetine (as a hydrochloride salt). A randomized, crossover design with a 2-week wash-out period between each dose was applied. Serum samples, obtained before dosing and at various appropriate time points up to 192 hours, were analyzed for fluoxetine and norfluoxetine content by a simple, accurate and precise HPLC method. ANOVA, power analysis, 90% confidence intervals (CI), and two one-sided tests were used for the statistical analysis of pharmacokinetic parameters. The tolerability of the preparations was good. The respective point estimates of the ratios of the geometric means of log-Cmax and log-AUC(0-infinity) of fluoxetine were 0.912 and 0.935 with 90% of 0.838-0.992 and 0.857-1.020. The corresponding point estimates of norfluoxetine were 0.952 (90% CI = 0.843-1.075) and 0.904 (90% CI = 0.807-1.013), respectively. Since both 90% CI for the AUC(0-infinity). and Cmax geometric mean ratios of fluoxetine and norfluoxetine were included in the 80% to 125% interval proposed by the FDA the test drug (fluoxetine tablets) was considered bioequivalent to the reference one (Prozac capsules) according both to the rate and extent of absorption.

  7. Drug: D08165 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D08165 Drug Medetomidine (INN); Domitor [veterinary] C13H16N2 200.1313 200.2795 D08165.gif Analgesic [veteri...nary]; Hypnotic, sedative [veterinary] alpha2-adrenergic receptor agonist [HSA:150

  8. Drug: D08429 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D08429 Drug Proligestone (INN); Covinan [veterinary] (TN); Delvosteron [veterinary]... (TN) C24H34O4 386.2457 386.5244 D08429.gif Progestin veterinary medicine progesterone receptor agonist [HSA

  9. Drug: D04883 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D04883 Drug Medetomidine hydrochloride (USAN) C13H16N2. HCl 236.108 236.7405 D04883.gif Analgesic [veterinar...y]; Sedative [veterinary] veterinary medicine alpha2-adrenergic receptor agonist [H

  10. Are marketed topical metronidazole creams bioequivalent? Evaluation by in vivo microdialysis sampling and tape stripping methodology

    DEFF Research Database (Denmark)

    Garcia Ortiz, Patricia Elodia; Hansen, S H; Shah, Surendra P.

    2011-01-01

    To evaluate the bioequivalence of 3 marketed topical metronidazole formulations by simultaneous dermal microdialysis and stratum corneum sampling by the tape stripping methodology, and to compare the techniques as tools for the determination of bioequivalence....

  11. Veterinary Technologists and Technicians

    Science.gov (United States)

    ... State & Area Data Explore resources for employment and wages by state and area for veterinary technologists and technicians. Similar Occupations Compare the job duties, education, job growth, and pay of veterinary technologists and ...

  12. NIGERIAN VETERINARY JOURNAL

    African Journals Online (AJOL)

    ADEYEYE

    Department of Veterinary Pathology and Microbiology; Faculty of Veterinary Medicine, Universiti Putra Malaysia, ... Parasitic diseases have a debilitating impact on human and animal health worldwide particularly in developing countries. Haemoparasitism have largely been ..... exerts a major health concern in domestic.

  13. Generics Substitution, Bioequivalence Standards, and International Oversight: Complex Issues Facing the FDA.

    Science.gov (United States)

    Bate, Roger; Mathur, Aparna; Lever, Harry M; Thakur, Dinesh; Graedon, Joe; Cooperman, Tod; Mason, Preston; Fox, Erin R

    2016-03-01

    The regulations for assessing the quality of generic drugs and their bioequivalence to innovator products are outdated and need to be substantially modernized. There are multiple reasons why these changes are needed, including: (i) the regulations remain largely unchanged since the passage of the Hatch-Waxman Act in 1984; (ii) medication therapies have become substantially more complex over the three decades since the passage of the Act; (iii) a switch from an innovator drug to a generic drug, or switching from one generic to another, is not a benign process - there is substantial clinical professional judgment involved and in some instances these decisions should be better informed; and (iv) pharmaceutical ingredients for finished products, whether innovator or generic, are from multiple sources of supply, adding variability in their production, and which may not be accounted for in specification tolerances. When these elements are viewed together, they clearly suggest that more transparency of responsible manufacturers in product labels and updated standards for bioequivalence are required. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Wide-scope analysis of veterinary drug and pesticide residues in animal feed by liquid chromatography coupled to quadrupole-time-of-flight mass spectrometry.

    Science.gov (United States)

    Aguilera-Luiz, María M; Romero-González, Roberto; Plaza-Bolaños, Patricia; Martínez Vidal, José Luis; Garrido Frenich, Antonia

    2013-08-01

    A fast and generic method has been developed for the simultaneous monitoring of >250 pesticides and veterinary drugs (VDs) in animal feed. A 'dilute-and-shoot' extraction with water and acetonitrile (1% formic acid) followed by a clean-up step with Florisil cartridges was applied. The extracts were analysed by ultra-high performance liquid chromatography coupled to hybrid analyser quadrupole-time-of-flight mass spectrometry using both positive and negative electrospray ionisation. The detection of the residues was accomplished by retention time and accurate mass using an in-house database. The identification of the detected compounds was carried out by searching of fragment ions for each compound and isotopic pattern. The optimised method was validated and recoveries ranged from 60% to 120% at three concentrations (10, 50 and 100 μg kg(-1)) for 30%, 68% and 80% of compounds, respectively, included in the database (364) in chicken feed. Document SANCO 12495/2011 and Directive 2002/657/CE were used as guidelines for method validation. Intra-day and inter-day precisions, expressed as relative standard deviations, were lower than 20% for more than 90% of compounds. The limits of quantification ranged from 4 to 200 μg kg(-1) for most analytes, which are sufficient to verify compliance of products with legal tolerances. The applicability of the procedure was further tested on different types of feed (chicken, hen, rabbit and horse feed), evaluating recoveries and repeatability. Finally, the method was applied to the analysis of 18 feed samples, detecting some VDs (sulfadiazine, trimethoprim, robenidin and monensin Na) and only one pesticide (chlorpyrifos).

  15. Are marketed topical metronidazole creamas bioequivalent ? Evaluation by in vivo microdialysis sampling and tape stripping methodology

    DEFF Research Database (Denmark)

    Ortiz, P. Garcia; Hansen, Steen Honore'; Shah, V. P.

    2011-01-01

    To evaluate the bioequivalence of 3 marketed topical metronidazole formulations by simultaneous dermal microdialysis and stratum corneum sampling by the tape stripping methodology, and to compare the techniques as tools for the determination of bioequivalence.......To evaluate the bioequivalence of 3 marketed topical metronidazole formulations by simultaneous dermal microdialysis and stratum corneum sampling by the tape stripping methodology, and to compare the techniques as tools for the determination of bioequivalence....

  16. Veterinary practice marketeer.

    Science.gov (United States)

    Phillips, Justin

    2015-01-24

    Justin Phillips is marketing manager at White Cross Vets and the Veterinary Marketing Association's (VMA's) Young Veterinary Marketeer of the Year. Here, he describes what he does and why he believes other practices should embrace marketing to improve their quality and client care. British Veterinary Association.

  17. Nigerian Veterinary Journal

    African Journals Online (AJOL)

    The Nigerian Veterinary Journal (NVJ) has been in existence since 1971. The NVJ is published by the Nigerian Veterinary Medical Association (NVMA) as part of the association's commitment to the advancement of Veterinary Medicine in Nigeria and other parts of the world, with a general view of enhancing the livestock ...

  18. Tanzania Veterinary Journal

    African Journals Online (AJOL)

    The Tanzania Veterinary Journal (The Tropical Veterinarian) is a biannual Journal, which publishes original contribution to knowledge on Veterinary Science, Animal Science and Production, and allied sciences including new techniques and developments in Veterinary Medicine. The target readers of the Journal are the ...

  19. NIGERIAN VETERINARY JOURNAL

    African Journals Online (AJOL)

    ADEYEYE

    1Department of Veterinary Anatomy, Michael Okpara University of Agriculture, Umudike, Nigeria, 2Department of. Veterinary Anatomy ... laboratory technologists and academic staff of the departments of veterinary anatomy, pathology and public health. Design of the ... Early histology and histopathology based research was ...

  20. NIGERIAN VETERINARY JOURNAL

    African Journals Online (AJOL)

    ADEYEYE

    Nigerian Veterinary Journal 38(2). 2017. Mustapha et al. 129 ... 1 Department of Veterinary Anatomy, College of Veterinary Medicine, Federal University of Agriculture Abeokuta,. Abeokuta, Ogun State; 2 ..... lamina 9; IB: Internal basilar nucleus; ICI: Intercalated nucleus; ICo9: Intercostal muscle motor neurons of lamina 9; ...

  1. NIGERIAN VETERINARY JOURNAL

    African Journals Online (AJOL)

    ADEYEYE

    Nigerian Veterinary Journal 37(3). 2016. Thomas et al. 123 .... Veterinary Medicine, Federal University of. Agriculture Abeokuta and were ..... immunogenic Salmonella ghost confers protection against internal organ colonization and egg contamination. Veterinary immunology and immunopathology,. 162(1-2): 41–50. JOSHI ...

  2. NIGERIAN VETERINARY JOURNAL

    African Journals Online (AJOL)

    ADEYEYE

    1288. NIGERIAN VETERINARY JOURNAL. ISSN 0331-3026. Nig. Vet. J., December 2015. Vol. 36 (4): 1288-1298. ORIGINAL ARTICLE. Anatomical Studies of ... 1Veterinary Teaching Hospital, Faculty of Veterinary Medicine, University of Ilorin, Ilorin, Nigeria; 2 Department of .... back, the internal organs were measured in.

  3. Solid state NMR and bioequivalence comparison of the pharmacokinetic parameters of two formulations of clindamycin

    KAUST Repository

    Al-Talla, Zeyad

    2011-01-01

    Objective: The purpose of this study was to compare the pharmacokinetic parameters and determine the bioequivalence of a generic formulation of clindamycin that is sold in the local markets in the Middle East (Clindox® 150 mg capsule; test) with a reference formulation (Dalacin C® 150 mg capsule) in healthy adult male volunteers. Methods: A single-dose, open-label, 2-period crossover study was conducted. Healthy male volunteers were randomly assigned to oral administration of a single treatment of the reference and test formulations. The same groups were given the alternate formulation. After dosing, serial blood samples were withdrawn for a period of 24 h. Serum harvested from the blood samples was analyzed for clindamycin by high performance liquid chromatography (HPLC) with ultraviolet detection. Pharmacokinetic parameters, including AUC0-∞, AUC 0-t, Cmax, Ke, tmax and t 1/2 were determined from the serum concentrations for both formulations (test and reference). The products were tested for bioequivalence after log-transformation of the data. Results: 24 healthy adult male volunteers from Jordan (mean [SD] age, 28.8 (7.7) years (range 19-45 years); height, 175.8 (10.6) cm (range 159.0-192.0 cm); weight, 75.6 (11.0) kg (range 58-101 kg); and body mass index, 24.4 (1.8) kg/m2 (range 21.3-28 kg/m2)) were enrolled in and completed the study. The 13C NMR spectra for both Dalacin C® and Clindox® showed 18 distinct lines associated with the 18 different carbon atoms. Conclusion: The statistical comparison suggested that Clindox® capsules are bioequivalent to Dalacin C® capsules. The 13C CPMAS results confirmed that the two drugs exhibit typical clindamycin spectra. ©2011 Dustri-Verlag Dr. K. Feistle.

  4. Influence of point estimates and study power of bioequivalence studies on establishing bioequivalence between generics by adjusted indirect comparisons.

    Science.gov (United States)

    Gwaza, Luther; Gordon, John; Potthast, Henrike; Welink, Jan; Leufkens, Hubert; Stahl, Matthias; García-Arieta, Alfredo

    2015-09-01

    Adjusted indirect comparisons can be used to investigate bioequivalence between generic products that are bioequivalent with a common reference product. In previous work with generic tuberculosis medicines prequalified by the WHO, it was observed that although indirect comparisons are an effective approach for confirming the interchangeability of generics, the approach is subject to less precision than direct comparisons. The objective of this investigation was to explore this by examining the influence of point estimates and power of bioequivalence studies versus the reference on the ability to show equivalence in indirect comparisons. Power was considered as a determining factor instead of variability and sample size, because sample size is calculated based on variability and desired power. Scenarios were computed combining a range of point estimate differences (0-14 %) and statistical power of the studies (50-99.99 %). The indirect comparisons could conclude equivalence between generics only when (a) point estimate differences between generics were low (≤ 5.5 %) for any sufficiently powered study (> 80 %), or (b) the differences were large (but less than 14 %) and both bioequivalence studies were overpowered (e.g., 10 % difference and power ≥ 95 %). In summary, the ability to demonstrate interchangeability between generics is dependent not only on the real differences between the products but also on the design of the original generic vs. reference bioequivalence studies being combined, as earmarked by their respective power.

  5. 75 FR 58411 - Center for Veterinary Medicine eSubmitter Workshop; Public Workshop; Request for Comments

    Science.gov (United States)

    2010-09-24

    ... HUMAN SERVICES Food and Drug Administration Center for Veterinary Medicine eSubmitter Workshop; Public...: ``Center for Veterinary Medicine (CVM) eSubmitter Workshop.'' The purpose of the public workshop is to..., Center for Veterinary Medicine (HFV-100), Food and Drug Administration, 7520 Standish Pl., Rockville, MD...

  6. 78 FR 14801 - Veterinary Oversight of Antimicrobial Use in Livestock: Impact on Stakeholders; Public Meetings...

    Science.gov (United States)

    2013-03-07

    ... HUMAN SERVICES Food and Drug Administration Veterinary Oversight of Antimicrobial Use in Livestock... areas that may lack access to adequate veterinary services. The meetings are jointly sponsored by FDA...: Patricia Arnwine, Center for Veterinary Medicine (HFV-6), Food and Drug Administration, 7519 Standish Pl...

  7. 77 FR 22247 - Veterinary Feed Directive; Draft Text for Proposed Regulation

    Science.gov (United States)

    2012-04-13

    ... HUMAN SERVICES Food and Drug Administration 21 CFR Part 558 Veterinary Feed Directive; Draft Text for... draft text for a proposed regulation intended to improve the efficiency of FDA's Veterinary Feed... CONTACT: Sharon Benz, Center for Veterinary Medicine (HFV-220), Food and Drug Administration, 7519...

  8. Two-stage designs for cross-over bioequivalence trials.

    Science.gov (United States)

    Kieser, Meinhard; Rauch, Geraldine

    2015-07-20

    The topic of applying two-stage designs in the field of bioequivalence studies has recently gained attention in the literature and in regulatory guidelines. While there exists some methodological research on the application of group sequential designs in bioequivalence studies, implementation of adaptive approaches has focused up to now on superiority and non-inferiority trials. Especially, no comparison of the features and performance characteristics of these designs has been performed, and therefore, the question of which design to employ in this setting remains open. In this paper, we discuss and compare 'classical' group sequential designs and three types of adaptive designs that offer the option of mid-course sample size recalculation. A comprehensive simulation study demonstrates that group sequential designs can be identified, which show power characteristics that are similar to those of the adaptive designs but require a lower average sample size. The methods are illustrated with a real bioequivalence study example. Copyright © 2015 John Wiley & Sons, Ltd.

  9. A critical assessment of the performance criteria in confirmatory analysis for veterinary drug residue analysis using mass spectrometric detection in selected reaction monitoring mode.

    Science.gov (United States)

    Berendsen, Bjorn J A; Meijer, Thijs; Wegh, Robin; Mol, Hans G J; Smyth, Wesley G; Armstrong Hewitt, S; van Ginkel, Leen; Nielen, Michel W F

    2016-05-01

    Besides the identification point system to assure adequate set-up of instrumentation, European Commission Decision 2002/657/EC includes performance criteria regarding relative ion abundances in mass spectrometry and chromatographic retention time. In confirmatory analysis, the relative abundance of two product ions, acquired in selected reaction monitoring mode, the ion ratio should be within certain ranges for confirmation of the identity of a substance. The acceptable tolerance of the ion ratio varies with the relative abundance of the two product ions and for retention time, CD 2002/657/EC allows a tolerance of 5%. Because of rapid technical advances in analytical instruments and new approaches applied in the field of contaminant testing in food products (multi-compound and multi-class methods) a critical assessment of these criteria is justified. In this study a large number of representative, though challenging sample extracts were prepared, including muscle, urine, milk and liver, spiked with 100 registered and banned veterinary drugs at levels ranging from 0.5 to 100 µg/kg. These extracts were analysed using SRM mode using different chromatographic conditions and mass spectrometers from different vendors. In the initial study, robust data was collected using four different instrumental set-ups. Based on a unique and highly relevant data set, consisting of over 39 000 data points, the ion ratio and retention time criteria for applicability in confirmatory analysis were assessed. The outcomes were verified based on a collaborative trial including laboratories from all over the world. It was concluded that the ion ratio deviation is not related to the value of the ion ratio, but rather to the intensity of the lowest product ion. Therefore a fixed ion ratio deviation tolerance of 50% (relative) is proposed, which also is applicable for compounds present at sub-ppb levels or having poor ionisation efficiency. Furthermore, it was observed that retention time

  10. Clarithromycin bioequivalence study of two oral formulations in healthy human volunteers.

    Science.gov (United States)

    Lerner, F E; Caliendo, G; Santagada, V; Santana GSM; Moraes MEA; De Nucci, G

    2000-07-01

    clarithromycin or 14-hydroxyclarithromycin, we suggest that future bioequivalence trials of this drug may be performed by quantifying clarithromycin only.

  11. Pediatric Exposures to Veterinary Pharmaceuticals.

    Science.gov (United States)

    Tomasi, Suzanne; Roberts, Kristin J; Stull, Jason; Spiller, Henry A; McKenzie, Lara B

    2017-03-01

    To describe the epidemiology of veterinary pharmaceutical-related exposures to children based on calls to a regional poison control center. A retrospective analysis of pediatric (≤19 years of age) exposures to pharmaceutical products intended for animal use, managed by a regional poison control center from 1999 through 2013, was conducted. Case narratives were reviewed and coded for exposure-related circumstances and intended species. Descriptive statistics were generated. From 1999 through 2013, the Central Ohio Poison Center received 1431 calls that related to a veterinary pharmaceutical exposure for children ≤19 years of age. Most of the pediatric calls (87.6%) involved children ≤5 years of age. Exploratory behavior was the most common exposure-related circumstance (61.4%) and ingestion accounted for the exposure route in 93% of cases. Substances commonly associated with exposures included: veterinary drugs without human equivalent (17.3%), antimicrobial agents (14.8%), and antiparasitics (14.6%). Based on substance and quantity, the majority of exposures (96.9%) were not expected to result in long-term or lasting health effects and were managed at home (94.1%). A total of 80 cases (5.6%) were referred to a health care facility, and 2 cases resulted in a moderate health effect. Children ≤5 years of age are most at risk for veterinary pharmaceutical-related exposures. Although most exposures do not result in a serious medical outcome, efforts to increase public awareness, appropriate product dispensing procedures, and attention to home storage practices may reduce the risk of veterinary pharmaceutical exposures to young children. Copyright © 2017 by the American Academy of Pediatrics.

  12. Multi-class, multi-residue analysis of trace veterinary drugs in milk by rapid screening and quantification using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry.

    Science.gov (United States)

    Zhang, Yaqian; Li, Xiang; Liu, Xiaomao; Zhang, Jinjie; Cao, Yanzhong; Shi, Zhihong; Sun, Hanwen

    2015-12-01

    A simple and rapid multi-class multi-residue analytical method was developed for the screening and quantification of veterinary drugs in milk by ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS). A total of 90 veterinary drugs investigated belonged to almost 20 classes including lincomycins, macrolides, sulfonamides, quinolones, tetracyclines, β-agonists, β-lactams, sedatives, β-receptor antagonists, sex hormones, glucocorticoids, nitroimidazoles, benzimidazoles, nitrofurans, and some others. A modified quick, easy, cheap, effective, rugged, and safe (QuEChERS) procedure was developed for the sample preparation without the solid-phase extraction step. The linearity, sensitivity, accuracy, repeatability, and reproducibility of the method were fully validated. The response of the detector was linear for each target compound in a wide concentration range with a correlation coefficient (R(2)) of 0.9973 to 0.9999 (among them R(2)>0.999 for 73 of 90 analytes). The range of the limit of quantification for these compounds in the milk ranged from 0.10 to 17.30μg/kg. The repeatability and reproducibility were in the range of 2.11 to 9.62% and 2.76 to 13.9%, respectively. The average recoveries ranged from 72.62 to 122.2% with the RSD (n=6) of 1.30 to 9.61% at 3 concentration levels. For the screening method, the data of the precursor and product ions of the target analytes were simultaneously acquired under the all ions MS/MS mode in a single run. An accurate mass database for the confirmation and identification of the target compounds was established. The applicability of the screening method was verified by applying to real milk samples. The proposed analytical method allows the identification and confirmation of the target veterinary drugs at trace levels employing quick analysis time. Certain veterinary drugs were detected in some cases. Copyright © 2015 American Dairy Science Association. Published by

  13. Mechanistic Oral Absorption Modeling and Simulation for Formulation Development and Bioequivalence Evaluation: Report of an FDA Public Workshop.

    Science.gov (United States)

    Zhang, X; Duan, J; Kesisoglou, F; Novakovic, J; Amidon, G L; Jamei, M; Lukacova, V; Eissing, T; Tsakalozou, E; Zhao, L; Lionberger, R

    2017-08-01

    On May 19, 2016, the US Food and Drug Administration (FDA) hosted a public workshop, entitled "Mechanistic Oral Absorption Modeling and Simulation for Formulation Development and Bioequivalence Evaluation." The topic of mechanistic oral absorption modeling, which is one of the major applications of physiologically based pharmacokinetic (PBPK) modeling and simulation, focuses on predicting oral absorption by mechanistically integrating gastrointestinal transit, dissolution, and permeation processes, incorporating systems, active pharmaceutical ingredient (API), and the drug product information, into a systemic mathematical whole-body framework. © 2017 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

  14. Veterinary Services Program

    Data.gov (United States)

    Federal Laboratory Consortium — Mission:To provide quality veterinary medical care and environmental enrichment programs for all animals, representing nine different species.To provide guidance for...

  15. Pharmacokinetics and bioequivalence of 2 meloxicam oral dosage formulations in healthy adult horses.

    Science.gov (United States)

    Vivancos, Melanie; Barker, Jessica; Engbers, Sarah; Fischer, Carrie; Frederick, Jami; Friedt, Heather; Rybicka, Joanna M; Stastny, Tereza; Banse, Heidi; Cribb, Alastair E

    2015-07-01

    Meloxicam, a non-steroidal anti-inflammatory drug, is approved for use in horses in several countries, but an equine formulation is not available in North America. However, meloxicam is being used in an extra-label manner in horses in Canada. The purpose of this study, therefore, was to assess the bioequivalence of an approved oral meloxicam suspension (Metacam 15 mg/mL for horses; Boehringer Ingelheim Vetmedica GmBH, Ingelheim, Germany) from the European Union with human meloxicam tablets (Meloxicam 15 mg tablets; TEVA Canada, Toronto, Ontario) compounded with molasses to improve palatability and administration. The geometric mean ratios (GMR test/reference) and the 90% confidence intervals of the pivotal pharmacokinetic parameters (area under the curve and maximum concentration) were within the defined limits of 80% to 125% generally accepted for products to be considered bioequivalent. Therefore, use of human meloxicam tablets compounded with molasses would be expected to produce a similar clinical response in horses as the approved oral product from the European Union.

  16. The role of the upper sample size limit in two-stage bioequivalence designs.

    Science.gov (United States)

    Karalis, Vangelis

    2013-11-01

    Two-stage designs (TSDs) are currently recommended by the regulatory authorities for bioequivalence (BE) assessment. The TSDs presented until now rely on an assumed geometric mean ratio (GMR) value of the BE metric in stage I in order to avoid inflation of type I error. In contrast, this work proposes a more realistic TSD design where sample re-estimation relies not only on the variability of stage I, but also on the observed GMR. In these cases, an upper sample size limit (UL) is introduced in order to prevent inflation of type I error. The aim of this study is to unveil the impact of UL on two TSD bioequivalence approaches which are based entirely on the interim results. Monte Carlo simulations were used to investigate several different scenarios of UL levels, within-subject variability, different starting number of subjects, and GMR. The use of UL leads to no inflation of type I error. As UL values increase, the % probability of declaring BE becomes higher. The starting sample size and the variability of the study affect type I error. Increased UL levels result in higher total sample sizes of the TSD which are more pronounced for highly variable drugs. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. A randomized, single-blind, Phase I trial (INVICTAN-1) assessing the bioequivalence and safety of BI 695502, a bevacizumab biosimilar candidate, in healthy subjects.

    Science.gov (United States)

    Hettema, Willem; Wynne, Christopher; Lang, Benjamin; Altendorfer, Mario; Czeloth, Niklas; Lohmann, Ragna; Athalye, Sandeep; Schliephake, Dorothee

    2017-08-01

    This Phase I trial (INVICTAN®-1) evaluated three-way bioequivalence and safety of BI 695502 a bevacizumab biosimilar candidate, and reference product bevacizumab from two sources (US-approved Avastin®, Genentech; EU-approved Avastin, Roche). Healthy male subjects (N = 91) were randomized 1:1:1 to receive a single intravenous infusion of 1 mg/kg of BI 695502 or US- or EU-approved Avastin. An interim analysis was planned when ~50% of subjects were evaluable for the primary end point to determine if the prespecified criteria for bioequivalence were achieved; if demonstrated, the study could be stopped early. The primary end point was area under the concentration-time curve (AUC) of the analyte in plasma from time zero extrapolated to infinity (AUC0-∞). Other pharmacokinetic (PK) parameters, safety, and in vitro binding affinity were also evaluated. The interim analysis demonstrated three-way bioequivalence for all comparisons. The confidence intervals around the geometric mean ratios of the primary and secondary PK parameters were within the predefined acceptance ranges. Study drugs were well tolerated with no clinically relevant differences in safety. BI 695502 and US- and EU-approved Avastin showed three-way bioequivalence with similar safety profile. NCT01608087.

  18. Veterinary microbiology and microbial disease

    National Research Council Canada - National Science Library

    Quinn, P. J

    2011-01-01

    "Veterinary Microbiology is one of the core subjects for veterinary students. Fully revised and expanded, this new edition covers every aspect of veterinary microbiology for students in both paraclinical and clinical years...

  19. Sahel Journal of Veterinary Sciences

    African Journals Online (AJOL)

    The Sahel Journal of Veterinary Sciences is the official journal of the Faculty of Veterinary Medicine, University of Maiduguri, Maiduguri, Nigeria. The journal welcomes original research articles, short communications and reviews on all aspects of veterinary sciences and related disciplines.

  20. Chitosan from shrimp shells: A renewable sorbent applied to the clean-up step of the QuEChERS method in order to determine multi-residues of veterinary drugs in different types of milk.

    Science.gov (United States)

    Arias, Jean Lucas de Oliveira; Schneider, Antunielle; Batista-Andrade, Jahir Antonio; Vieira, Augusto Alves; Caldas, Sergiane Souza; Primel, Ednei Gilberto

    2018-02-01

    Clean extracts are essential in LC-MS/MS, since the matrix effect can interfere in the analysis. Alternative materials which can be used as sorbents, such as chitosan in the clean-up step, are cheap and green options. In this study, chitosan from shrimp shell waste was evaluated as a sorbent in the QuEChERS method in order to determine multi-residues of veterinary drugs in different types of milk, i. e., fatty matrices. After optimization, the method showed correlation coefficients above 0.99, LOQs ranged between 1 and 50μgkg-1 and recoveries ranged between 62 and 125%, with RSD<20% for all veterinary drugs in all types of milk under study. The clean-up step which employed chitosan proved to be effective, since it reduced both the matrix effect (from values between -40 and -10% to values from -10 to +10%) and the extract turbidity (up to 95%). When the proposed method was applied to different milk samples, residues of albendazole (49μgkg-1), sulfamethazine (

  1. Update on the safety and bioequivalence of biosimilars – focus on enoxaparin

    Directory of Open Access Journals (Sweden)

    Jeske W

    2013-06-01

    Full Text Available Walter Jeske,1 Jeanine M Walenga,1 Debra Hoppensteadt,2 Jawed Fareed2 1Cardiovascular Institute; 2Department of Pathology, Loyola University Chicago, Maywood, IL, USA Abstract: Generic forms of chemically-derived drugs must exhibit chemical identity and be bioequivalent in healthy human subjects. The use of generic drugs results in a considerable savings of healthcare expenditures. Biologic drugs are produced in living systems or are derived from biologic material and extend beyond proteins to include antibodies, polysaccharides, polynucleotides, and live viral material. Such drugs pose a challenge to characterize as they tend to be larger in size than chemically-derived drugs, can exhibit a variety of post-translational modifications, and can have activities that are dependent on specific conformations. Biosimilars are not true generics, but rather, exhibit a high degree of similarity to the reference product and are considered to be biologically and clinically comparable to the innovator product. Therefore, the development process for biosimilars is more complex than for a true generic. Guidance is now available from the US Food and Drug Administration and from the European Medicines Agency for the development of biosimilar drugs. Biosimilar drugs are expected to have a major impact in the management of various diseases in coming years. Keywords: generic, biosimilar, low molecular weight heparin

  2. NIGERIAN VETERINARY JOURNAL

    African Journals Online (AJOL)

    ADEYEYE

    Department of Veterinary Pathology, College of Veterinary Medicine, Michael Okpara University of Agriculture,. Umudike, P.M.B 7267 Umuahia, Abia State, Nigeria. *Corresponding author: Email: docoleji@yahoo.com; Tel. No:+234 8034509991. SUMMARY. This study investigated comparatively the genetic influence on the ...

  3. Archives: Nigerian Veterinary Journal

    African Journals Online (AJOL)

    Items 1 - 49 of 49 ... Archives: Nigerian Veterinary Journal. Journal Home > Archives: Nigerian Veterinary Journal. Log in or Register to get access to full text downloads. Username, Password, Remember me, or Register · Journal Home · ABOUT THIS JOURNAL · Advanced Search · Current Issue · Archives. 1 - 49 of 49 Items ...

  4. Nigerian Veterinary Journal (1)

    African Journals Online (AJOL)

    The importance of computers in all works of life need not to be overemphasized. However, in. Nigeria, the application of computers in veterinary medicine has not been fully utilized. Computer aided diagnosis is a process that has significantly improved the practice of veterinary medicine in other parts of the world. This paper ...

  5. Nigerian Veterinary Journal: Submissions

    African Journals Online (AJOL)

    SCOPE The Editorial Board of the Nigerian Veterinary Journal (NVJ) welcomes contributions in the form of original research papers, review articles, clinical case reports, and short communications on all aspects of Veterinary Medicine, Surgery and Animal Production. Submissions are accepted on the understanding that ...

  6. Archives: Ethiopian Veterinary Journal

    African Journals Online (AJOL)

    Items 1 - 16 of 16 ... Archives: Ethiopian Veterinary Journal. Journal Home > Archives: Ethiopian Veterinary Journal. Log in or Register to get access to full text downloads. Username, Password, Remember me, or Register · Journal Home · ABOUT THIS JOURNAL · Advanced Search · Current Issue · Archives. 1 - 16 of 16 Items ...

  7. Archives: Tanzania Veterinary Journal

    African Journals Online (AJOL)

    Items 1 - 15 of 15 ... Archives: Tanzania Veterinary Journal. Journal Home > Archives: Tanzania Veterinary Journal. Log in or Register to get access to full text downloads. Username, Password, Remember me, or Register · Journal Home · ABOUT THIS JOURNAL · Advanced Search · Current Issue · Archives. 1 - 15 of 15 Items ...

  8. NIGERIAN VETERINARY JOURNAL

    African Journals Online (AJOL)

    ADEYEYE

    Nigerian Veterinary Journal 37(3). 2016. Meseko et al. 155. NIGERIAN VETERINARY JOURNAL. ISSN 0331-3026. Nig. Vet. J., September 2016. Vol. 37 (3): 155-159. SHORT COMMUNICATION. Detection of Haemagglutination inhibition antibody to Pandemic and. Classical Swine Influenza Virus in Commercial Piggery in ...

  9. NIGERIAN VETERINARY JOURNAL

    African Journals Online (AJOL)

    ADEYEYE

    Nigerian Veterinary Journal 37(1). 2016. Igado et al. 54. NIGERIAN VETERINARY JOURNAL. ISSN 0331-3026. Nig. Vet. J., March 2016. Vol. 37 (1): 54-63. ORIGINAL ARTICLE. Cranio-facial and Ocular Morphometrics of the Male Greater Cane Rat. (Thryonomys swinderianus). Igado, O. O.. 1. *; Adebayo, A. O.. 2.

  10. NIGERIAN VETERINARY JOURNAL

    African Journals Online (AJOL)

    ADEYEYE

    Nigerian Veterinary Journal 37(3). 2016. Ogunro et al. 187. NIGERIAN VETERINARY JOURNAL. ISSN 0331-3026. Nig. Vet. J., September 2016. Vol. 37 (3): 187-191. CASE REPORT. Management of Epitheliogenesis Imperfecta in a Piglet (Sus Scrofa domesticus) in Ibadan, Nigeria. Ogunro, B. N.. 1. ; Otuh, P. I.. 1.

  11. NIGERIAN VETERINARY JOURNAL

    African Journals Online (AJOL)

    ADEYEYE

    Nigerian Veterinary Journal 38(2). 2017. Meseko et al. 124. NIGERIAN VETERINARY JOURNAL. ISSN 0331-3026. Nig. Vet. J., June 2017. Vol 38 (2): 124-128. SHORT COMMUNICATION. Fowlpox Virus from Backyard Poultry in Plateau State Nigeria: Isolation and Phylogeny of the P4b Gene Compared to a Vaccine Strain.

  12. Open Veterinary Journal

    African Journals Online (AJOL)

    Open Veterinary Journal is a peer reviewed international open access online and printed journal that publishes high-quality original research articles, reviews, short communications and case reports dedicated to all aspects of veterinary sciences and its related subjects. Other websites associated with this journal: ...

  13. Open Veterinary Journal: Contact

    African Journals Online (AJOL)

    Principal Contact. Dr. Ibrahim Eldaghayes Faculty of Veterinary Medicine, University of Tripoli Faculty of Veterinary Medicine, University of Tripoli, P. O. Box 13662, Tripoli, Libya Phone: +218 21 462 8422. Fax: +218 21 462 8421. Email: ibrahim.eldaghayes@vetmed.edu.ly ...

  14. NIGERIAN VETERINARY JOURNAL

    African Journals Online (AJOL)

    ADEYEYE

    variegatum (Acari: Ixodidae) Ticks from Nigeria. Ogo, N. I.. 1. ; Okubanjo, O. O.. 2. ; Inuwa, H. M.. 3 and Agbede, R. I. S.. 4. 1National Veterinary Research Institute, Vom, Plateau State. 2Department of Veterinary Parasitology and. Entomology, Ahmadu Bello University, Zaria, Nigeria. 3Department of Biochemistry, Ahmadu ...

  15. NIGERIAN VETERINARY JOURNAL

    African Journals Online (AJOL)

    ADEYEYE

    Vet. J., December 2015. Vol. 36 (4): 1272-1282. ORIGINAL ARTICLE. Gross and Morphometric Anatomical Changes of the Thyroid Gland in the West African Dwarf ... Department of Veterinary Anatomy, Faculty of Veterinary Medicine, University of Nigeria, Nsukka, Nigeria. .... common carotid artery, internal jugular vein,.

  16. NIGERIAN VETERINARY JOURNAL

    African Journals Online (AJOL)

    ADEYEYE

    Vet. J., March 2016. Vol. 37 (1): 45-53. ORIGINAL ARTICLE. A Retrospective Evaluation of Intravenous Fluid Usage in Animal. Patients Treated at Veterinary Teaching Hospital Nsukka, 2005-2015 ... 2Department of Veterinary Medicine, University of Nigeria, Nsukka. ... they carried with them their own internal sea.

  17. NIGERIAN VETERINARY JOURNAL

    African Journals Online (AJOL)

    ADEYEYE

    SUMMARY. The prevalence and morphological pathology of renal failure in exotic breeds of dog in Lagos and Ogun States, within Southwestern Nigeria were determined from postmortem records of the. Department of Veterinary Pathology, College of Veterinary Medicine, Federal University of. Agriculture, Abeokuta ...

  18. NIGERIAN VETERINARY JOURNAL

    African Journals Online (AJOL)

    ADEYEYE

    at the Maiduguri municipal abattoir and were used for this study. Thyroid glands collected were transported in ice packs to the Department of Veterinary Pathology laboratory, University of Maiduguri, Nigeria for gross examination and thereafter, fixed and sent to Department of Veterinary. Anatomy, University of Abuja, were it ...

  19. The basic regulatory considerations and prospects for conducting bioavailability/bioequivalence (BA/BE studies – an overview

    Directory of Open Access Journals (Sweden)

    Shaik Mastan

    2011-03-01

    Full Text Available Shaik Mastan1, Thirunagari Bhavya Latha2, Sathe Ajay11Cytel Statistical Software and Services Pvt Ltd, Pune, Maharashtra, India; 2Business Development, Bioserve Clinical Research Pvt Ltd, Hyderabad, Andhra Pradesh, IndiaAbstract: Bioavailability (BA and bioequivalence (BE studies play a major role in the drug development phase for both new drug products and their generic equivalents, and thus attract considerable attention globally. BE is a strategy to introduce generic equivalents of brand-name drugs (innovator drugs to lower the cost of medication through proper assessment as directed by the international regulatory authorities. There are several approaches to assess BE and each regulatory authority has its own regulations/guidance for conducting BA/BE studies before approving generic products for marketing in their country. Therefore, a thorough understanding is required of these BA/BE concepts and basic regulatory considerations for conducting BA/BE studies. This article briefly reviews the BA/BE concepts, approaches, designs, and various basic regulatory considerations and prospects for conducting BA/BE studies. Keywords: bioavailability, bioequivalence, generic drugs, regulatory authority, pharmacokinetics, pharmacodynamics 

  20. From Bioequivalence to Biosimilarity: The Rise of a Novel Regulatory Framework.

    Science.gov (United States)

    Karalis, V D

    2016-01-01

    One of the most crucial issues in pharmacotherapy is to address the query if a patient can be switched from one product to another of the same active substance. For the conventional small-molecule drugs, there is a consensus on the required bioequivalence criteria. However, proving equivalence in the field of biologicals is an issue with no clear harmony. The aim of this review is to highlight the differences between the biologicals and the conventional chemical drugs, as well as, to present the different regulatory requirements for the placement of biosimilars on the market.Biologicals are substantially larger than chemical compounds, their manufacturing process is very complex, and their protein structure may trigger immune reactions. For this reason, the conventional bioequivalence approach is not adequate, but further emphasis should be placed on the quality of the manufacturing process and the risks of immunogenicity. The assessment procedure of biosimilars should encompass their comparison with the innovator product using all available evidence derived from the development process. The latter includes analytical and animal studies, pharmacokinetic and pharmacodynamic data, as well as, clinical trials focusing on immunogenicity. The US FDA has established a step-wise approach to demonstrate biosimilarity, while the EMA has already issued many guidelines referring either to all biosimilars or to specific products/classes. Overall, a case-by-case assessment procedure is considered by the regulatory authorities. In any case the placement of a biosimilar on the market does not necessarily imply interchangeability with the innovator drug. © Georg Thieme Verlag KG Stuttgart · New York.

  1. 21 CFR 1308.26 - Excluded veterinary anabolic steroid implant products.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Excluded veterinary anabolic steroid implant... SCHEDULES OF CONTROLLED SUBSTANCES Excluded Veterinary Anabolic Steroid Implant Products § 1308.26 Excluded veterinary anabolic steroid implant products. (a) Products containing an anabolic steroid, that are expressly...

  2. 21 CFR 1308.25 - Exclusion of a veterinary anabolic steroid implant product; application.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Exclusion of a veterinary anabolic steroid implant... OF JUSTICE SCHEDULES OF CONTROLLED SUBSTANCES Excluded Veterinary Anabolic Steroid Implant Products § 1308.25 Exclusion of a veterinary anabolic steroid implant product; application. (a) Any person seeking...

  3. 76 FR 46818 - Agency Information Collection Activities; Proposed Collection; Comment Request; Veterinary Feed...

    Science.gov (United States)

    2011-08-03

    ... Collection; Comment Request; Veterinary Feed Directive AGENCY: Food and Drug Administration, HHS. ACTION... on reporting and recordkeeping requirements for distribution and use of Veterinary Feed Directive... technology. Veterinary Feed Directive--21 CFR Part 558 (OMB Control Number 0910- 0363)--Extension With the...

  4. Drug: D08150 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D08150 Drug Lufenuron (INN); Program [veterinary] (TN) C17H8Cl2F8N2O3 509.9784 511....1502 D08150.gif Antiparasitic [veterinary]; Insecticide [veterinary] Same as: C18434 veterinary medicine CAS

  5. "Pharmacodynamically evaluated bioequivalence of two preparations of Enalapril Maleate "

    Directory of Open Access Journals (Sweden)

    "Tajerzadeh H

    2001-07-01

    Full Text Available The bioequivalence of two preparations of enalapril maleate (20 mg tablets manufactured in Iran has been exploited in reference to a standard preparation (Xanef 20 tablets, MSD, Germany in 14 healthy volunteers. Following oral dosing of a single tablet of each of test and standard products, as a randomized crossover design with 10-day washout intervals, the blood samples were collected in predetermined time points and using a synthetic substrate, Hippuryl-Histidy-Leucine (HHL, the release of hippuric acid from the substrate was determined as Angiotensin-Converting-Enzyme (ACE activity of serum fractions. The percent of ACE inhibition in each sample was calculated and plotted against time, from which three pharmacodynamic parameters, i.e. Emax, tmax and AUC0-24 were derived. The results of statistical comparison of these parameters showed that both of the test preparations are bioequivalent with reference standard preparation.

  6. Optimal adaptive sequential designs for crossover bioequivalence studies.

    Science.gov (United States)

    Xu, Jialin; Audet, Charles; DiLiberti, Charles E; Hauck, Walter W; Montague, Timothy H; Parr, Alan F; Potvin, Diane; Schuirmann, Donald J

    2016-01-01

    In prior works, this group demonstrated the feasibility of valid adaptive sequential designs for crossover bioequivalence studies. In this paper, we extend the prior work to optimize adaptive sequential designs over a range of geometric mean test/reference ratios (GMRs) of 70-143% within each of two ranges of intra-subject coefficient of variation (10-30% and 30-55%). These designs also introduce a futility decision for stopping the study after the first stage if there is sufficiently low likelihood of meeting bioequivalence criteria if the second stage were completed, as well as an upper limit on total study size. The optimized designs exhibited substantially improved performance characteristics over our previous adaptive sequential designs. Even though the optimized designs avoided undue inflation of type I error and maintained power at ≥ 80%, their average sample sizes were similar to or less than those of conventional single stage designs. Copyright © 2015 John Wiley & Sons, Ltd.

  7. Lack of pharmacokinetic bioequivalence between generic and branded amoxicillin formulations. A post-marketing clinical study on healthy volunteers

    Science.gov (United States)

    Del Tacca, Mario; Pasqualetti, Giuseppe; Di Paolo, Antonello; Virdis, Agostino; Massimetti, Gabriele; Gori, Giovanni; Versari, Daniele; Taddei, Stefano; Blandizzi, Corrado

    2009-01-01

    AIMS There are concerns about the quality of generic drugs in the postmarketing setting. The aim was to establish whether two generic formulations of amoxicillin, available on the Italian market, fulfil the criteria for clinical pharmacokinetic bioequivalence vs. the branded drug. METHODS Two generic amoxicillin products (generic A and B) were selected among four fast-release tablet formulations available on the Italian market. Twenty-four healthy adult volunteers of either sex participated to a single-dose, randomized, three-treatment, crossover, single-blind bioequivalence study designed to compare generic A and B with branded amoxicillin. Plasma samples were collected at preset times for 24 h after dosing, and assayed for amoxicillin levels by high-performance liquid chromatography. RESULTS Ninety percent confidence intervals of AUC ratios were 0.8238, 1.0502 (ratio 0.9302) and 0.8116, 1.1007 (ratio 0.9452) for generic A and B vs. branded amoxicillin, respectively. Ninety percent confidence intervals of Cmax ratios were 0.7921, 1.0134 (ratio 0.8960) and 0.8246, 1.1199 (ratio 0.9610) for generic A and B vs. branded amoxicillin, respectively. The mean pharmacokinetic profiles showed that the AUC value of branded amoxicillin was 8.5 and 5.4% greater than that estimated for generic A and B, respectively. Few adverse events were recorded; these were not serious and occurred without apparent relationship to any specific amoxicillin formulation. CONCLUSIONS These results indicate that one of the two marketed amoxicillin generics analysed in the present study is not bioequivalent to the brand leader product for Cmax on the basis of single-dose pharmacokinetic assessment. PMID:19660001

  8. Lack of pharmacokinetic bioequivalence between generic and branded amoxicillin formulations. A post-marketing clinical study on healthy volunteers.

    Science.gov (United States)

    Del Tacca, Mario; Pasqualetti, Giuseppe; Di Paolo, Antonello; Virdis, Agostino; Massimetti, Gabriele; Gori, Giovanni; Versari, Daniele; Taddei, Stefano; Blandizzi, Corrado

    2009-07-01

    There are concerns about the quality of generic drugs in the postmarketing setting. The aim was to establish whether two generic formulations of amoxicillin, available on the Italian market, fulfil the criteria for clinical pharmacokinetic bioequivalence vs. the branded drug. Two generic amoxicillin products (generic A and B) were selected among four fast-release tablet formulations available on the Italian market. Twenty-four healthy adult volunteers of either sex participated to a single-dose, randomized, three-treatment, crossover, single-blind bioequivalence study designed to compare generic A and B with branded amoxicillin. Plasma samples were collected at preset times for 24 h after dosing, and assayed for amoxicillin levels by high-performance liquid chromatography. Ninety percent confidence intervals of AUC ratios were 0.8238, 1.0502 (ratio 0.9302) and 0.8116, 1.1007 (ratio 0.9452) for generic A and B vs. branded amoxicillin, respectively. Ninety percent confidence intervals of C(max) ratios were 0.7921, 1.0134 (ratio 0.8960) and 0.8246, 1.1199 (ratio 0.9610) for generic A and B vs. branded amoxicillin, respectively. The mean pharmacokinetic profiles showed that the AUC value of branded amoxicillin was 8.5 and 5.4% greater than that estimated for generic A and B, respectively. Few adverse events were recorded; these were not serious and occurred without apparent relationship to any specific amoxicillin formulation. These results indicate that one of the two marketed amoxicillin generics analysed in the present study is not bioequivalent to the brand leader product for C(max) on the basis of single-dose pharmacokinetic assessment.

  9. Telemedicine in veterinary practice

    Directory of Open Access Journals (Sweden)

    M. Mars

    2006-06-01

    Full Text Available Veterinary surgeons have a long tradition of consulting one another about problem cases and many have unwittingly practised telemedicine when discussing cases by telephone or by sending laboratory reports by telefax. Specific veterinary telemedicine applications have been in use since the early 1980s, but little research has been undertaken in this field. The Pubmed and CAB International databases were searched for the following Boolean logic-linked keywords; veterinary AND telemedicine, veterinary AND telecare, animal AND telemedicine, animal AND telecare and veterinary AND e-mail and an additional search was made of the worldwide web, using Google Scholar. This returned 25 papers which were reviewed. Of these only 2 report research. Sixteen papers had no references and 1 author was associated with 13 papers. Several themes emerge in the papers reviewed. These include remarks about the use of telemedicine, the benefits that can and are derived from the use of telemedicine, areas of practice in which telemedicine is being used, ethical and legal issues around the practice of telemedicine, image standards required for telemedicine, the equipment that is required for the practice of telemedicine, advice on ways in which digital images can be obtained and educational aspects of telemedicine. These are discussed. Veterinary practice has lagged behind its human counterpart in producing research on the validity and efficacy of telemedicine. This is an important field which requires further research.

  10. Bioequivalence assessment of ambroxol orally-disintegrating tablet after a single oral-dose administration to healthy volunteers.

    Science.gov (United States)

    Ni, Yaojun; Hou, Lili; Chen, Liang; Fan, Jiang

    2016-05-01

    In this study, a modified LC-MS/MS method was used to determine plasma ambroxol concentration and thereby examine the bioequivalence of two ambroxol medications among healthy Chinese male volunteers. The study used a single-dose, randomized, open-label design principle and calculated pharmacokinetic parameters for the comparison of the two formulations. Administration of a single oral dose of either the test drug or reference drug was found to be safe in healthy subjects. No severe, serious, or life-threatening clinical or drug-related side effects were reported during the study. The majority of clinical laboratory test results were within the normal range or not clinically significant. The pharmacokinetic parameters for ambroxol oral tablets and ambroxol orally disintegrating tablets were comparable. For the comparison of the two formulations, the 90% confidence intervals for the log-transformed pharmacokinetic parameters (Cmax, AUC0-t, and AUC0-inf) fell within the bioequivalenceambroxol oral tablets were bioequivalent to ambroxol orally-disintegrating tablets in healthy human adult male volunteers, under fasting conditions.

  11. Influence analysis on crossover design experiment in bioequivalence studies.

    Science.gov (United States)

    Huang, Yufen; Ke, Bo-Shiang

    2014-01-01

    Crossover designs are commonly used in bioequivalence studies. However, the results can be affected by some outlying observations, which may lead to the wrong decision on bioequivalence. Therefore, it is essential to investigate the influence of aberrant observations. Chow and Tse in 1990 discussed this issue by considering the methods based on the likelihood distance and estimates distance. Perturbation theory provides a useful tool for the sensitivity analysis on statistical models. Hence, in this paper, we develop the influence functions via the perturbation scheme proposed by Hampel as an alternative approach on the influence analysis for a crossover design experiment. Moreover, the comparisons between the proposed approach and the method proposed by Chow and Tse are investigated. Two real data examples are provided to illustrate the results of these approaches. Our proposed influence functions show excellent performance on the identification of outlier/influential observations and are suitable for use with small sample size crossover designs commonly used in bioequivalence studies. Copyright © 2013 John Wiley & Sons, Ltd.

  12. International Veterinary Epilepsy Task Force consensus proposal

    DEFF Research Database (Denmark)

    Bhatti, Sofie F M; De Risio, Luisa; Muñana, Karen

    2015-01-01

    with the initial drug is unsatisfactory, and 4) when treatment changes should be considered. In this consensus proposal, an overview is given on the aim of AED treatment, when to start long-term treatment in canine epilepsy and which veterinary AEDs are currently in use for dogs. The consensus proposal for drug...... for the management of canine idiopathic epilepsy. Furthermore, for the management of structural epilepsy AEDs are inevitable in addition to treating the underlying cause, if possible....

  13. 21 CFR 510.112 - Antibiotics used in veterinary medicine and for nonmedical purposes; required data.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Antibiotics used in veterinary medicine and for... DRUGS Specific Administrative Rulings and Decisions § 510.112 Antibiotics used in veterinary medicine... Medical and Nonmedical Uses of Antibiotics, was formed by the Food and Drug Administration to study, and...

  14. Pharmacokinetics and bioequivalence of a pregabalin 150-mg capsule in healthy Thai subjects.

    Science.gov (United States)

    Prompila, Nantaporn; Eiamart, Wanna; Jumroen, Yaowatree; Sayankuldilok, Nonlanee; Chariyavilaskul, Pajaree; Ketchat, Wannarasami; Wittayalertpanya, Supeecha

    2017-10-01

    The purpose of the study was to evaluate the pharmacokinetics and bioequivalence of pregabalin following administration of a 150-mg capsule of test and reference products. The study was designed as a randomized, two-treatment, two-period, two-sequence, single-dose crossover with 1-week washout period between period I and period II dosing. 20 healthy male and female Thai subjects were enrolled in the study. Each subject was in fasted state for ~ 10 hours prior to receiving a single oral 150-mg pregabalin capsule. Serial blood samples were collected at pre-dose until 32 hours after drug administration. Plasma samples were extracted by protein precipitation and derivatized with 4-chloro-7-nitrobenzofurazan. Pregabalin plasma concentrations were determined by HPLC method, and pharmacokinetic parameters were calculated. For bioequivalence assessment, the differences of Cmax, AUC0-t, and AUC0-inf means based on ln-transformed data were assessed by the 90% confidence interval (CI). Pharmacokinetic parameters were determined that test and reference products showed 0.96 ± 0.35 and 1.04 ± 0.96 hours for tmax, 4,594.217 ± 834.195 and 4,568.68 ± 573.963 ng/mL for Cmax, 30,048.150 ± 2,998.920 and 29,315.722 ± 2,747.396 ng×h/mL for AUC0-t, 30,594.210 ± 2,872.317 and 29,831.454 ± 2,688.020 ng×h/mL for AUC0-inf, respectively. The 90% CIs of Cmax, AUC0-t, and AUC0-inf for test and reference products were assessed at 95.356 - 104.630%, 99.303 - 105.751%, and 99.373 - 105.788%, respectively. The results were within the acceptance criteria of 80 - 125%. Pharmacokinetic parameters of a single oral 150-mg pregabalin capsule in healthy Thai subjects were evaluated and showed rapid absorption. 90% CI for the differences of Cmax, AUC0-t, and AUC0-inf were within the acceptable range of the criteria so that bioequivalence of the test and reference products of pregabalin 150-mg capsule could be concluded.
.

  15. Database on veterinary clinical research in homeopathy.

    Science.gov (United States)

    Clausen, Jürgen; Albrecht, Henning

    2010-07-01

    The aim of the present report is to provide an overview of the first database on clinical research in veterinary homeopathy. Detailed searches in the database 'Veterinary Clinical Research-Database in Homeopathy' (http://www.carstens-stiftung.de/clinresvet/index.php). The database contains about 200 entries of randomised clinical trials, non-randomised clinical trials, observational studies, drug provings, case reports and case series. Twenty-two clinical fields are covered and eight different groups of species are included. The database is free of charge and open to all interested veterinarians and researchers. The database enables researchers and veterinarians, sceptics and supporters to get a quick overview of the status of veterinary clinical research in homeopathy and alleviates the preparation of systematical reviews or may stimulate reproductions or even new studies. 2010 Elsevier Ltd. All rights reserved.

  16. Confidence in generic drug substitution.

    Science.gov (United States)

    Lionberger, R; Jiang, W; Huang, S-M; Geba, G

    2013-10-01

    Patients should have confidence that the generic drugs they are prescribed in the United States can be effectively substituted for the brand product or another generic product. Through new bioequivalence study designs for narrow therapeutic index (NTI) drugs and postapproval studies of generic substitution, the US Food and Drug Administration's (FDA's) ongoing generic drug regulatory science activities are designed to ensure successful generic substitution for all drug products.

  17. Global veterinary leadership.

    Science.gov (United States)

    Wagner, G Gale; Brown, Corrie C

    2002-11-01

    The public needs no reminder that deadly infectious diseases such as FMD could emerge in any country at any moment, or that national food security could be compromised by Salmonella or Listeria infections. Protections against these risks include the knowledge that appropriate and equivalent veterinary education will enable detection and characterization of emerging disease agents, as well as an appropriate response, wherever they occur. Global veterinary leadership is needed to reduce the global threat of infectious diseases of major food animal and public health importance. We believe that the co-curriculum is an excellent way to prepare and train veterinarians and future leaders who understand and can deal with global issues. The key to the success of the program is the veterinarian's understanding that there is a cultural basis to the practice of veterinary medicine in any country. The result will be a cadre of veterinarians, faculty, and other professionals who are better able (language and culture) to understand the effects of change brought about by free trade and the importance of interdisciplinary and institutional relationships to deal effectively with national and regional issues of food safety and security. New global veterinary leadership programs will build on interests, experience, ideas, and ambitions. A college that wishes to take advantage of this diversity must offer opportunities that interest veterinarians throughout their careers and that preferably connect academic study with intensive experiential training in another country. At its best, the global veterinary leadership program would include a partnership between veterinarians and several international learning centers, a responsiveness to the identified international outreach needs of the profession, and attention to critical thinking and reflection. The global veterinary leadership program we have described is intended to be a set of ideas meant to promote collaboration, coalitions, and

  18. Pharmacokinetics and bioequivalence of two suxibuzone oral dosage forms in horses.

    Science.gov (United States)

    Jaraiz, V; Rodriguez, C; San Andres, M D; Gonzalez, F; San Andres, M I

    1999-08-01

    A disposition and bioequivalence study with a suxibuzone granulated and a suxibuzone paste oral formulation was performed in horses. Suxibuzone (SBZ) is a nonsteroidal anti-inflammatory drug, which was administered to horses (n = 6) at a dosage of 19 mg/kg bwt by the oral route (p.o.) in a two period cross-over design. Suxibuzone is very rapidly transformed into its main active metabolites, phenylbutazone (PBZ) and oxyphenbutazone (OPBZ). Therefore plasma and synovial fluid concentrations of SBZ, PBZ and OPBZ were simultaneously measured by a sensitive and specific high-performance liquid chromatographic method. The pharmacokinetic parameters were determined by noncompartmental analysis. Suxibuzone could not be detected in any plasma and synovial fluid samples (LOQ) was 608.0 +/- 162.2 micrograms.h/mL and 656.6 +/- 149.7 micrograms.h/mL after granulate and paste administration, respectively. Mean plasma concentration of OPBZ increased to 5-6.7 micrograms/mL, with the maximum concentration (Cmax) appearing between 9 and 12 h after administration of both formulations. The AUCs0-->LOQ for OPBZ were also similar (141.8 +/- 48.3 micrograms.h/mL granulate vs. 171.4 +/- 45.0 micrograms.h/mL paste). It was concluded that the suxibuzone products were bioequivalent with respect to PBZ. For OPBZ, the 95% confidence intervals of the pharmacokinetic parameters were within the acceptable range of 80-125%. The paste formulation provided greater bioavailability of PBZ and OPBZ.

  19. Development of stabilized tenofovir disoproxil tablet: degradation profile, stabilization, and bioequivalence in beagle dogs.

    Science.gov (United States)

    Oh, Ga-Hui; Kim, Joo-Eun; Park, Young-Joon

    2017-12-25

    The purpose of this study was to develop a hydrolysis-resistant optimized oral formulation of tenofovir disoproxil (TD) using a stabilizer. To develop a stabilized TD tablet bioequivalent to the commercial TD fumarate (TDF, Viread ® ) tablet, TD free base was prepared and its degradation profile and stability were investigated. The TD tablet showed antiviral activity, but its absorption was limited in the intestinal tract because of premature degradation. The drug subjected to severe conditions for the stress test was catalyzed under neutral, basic, oxidative, and thermolytic conditions, whereas it was comparatively stable under acidic, photolytic, and humid states. The compatibility study showed that sodium bisulfite (SB) stabilized TD by preventing its degradation in aqueous and 3% peroxide solutions compared with the unstabilized TD. According to the stability analysis and degradation profile, four TD tablet formulations were prepared. The selected TD tablets were composed of non-hygroscopic excipients (lipophilic-fumed silica, anhydrous lactose, and microcrystalline cellulose [MCC]), SB, croscarmellose sodium (CCS), and hydrogenated castor oil (HCO), and were manufactured using a dry granulation method because of their hydrolytic properties. The stabilized TD tablet showed similar dissolution properties as the TDF (Viread ® ) reference tablet in pH 1.2, 4.0, and 6.8 and water. Moreover, the lower degradation rate of the tablet in simulated gastrointestinal fluid demonstrated that its intestinal absorption might have improved owing to prevention of its enzymatic hydrolysis and the pH effect. Finally, the formulated TD tablet was bioequivalent to the TDF (Viread ® ) reference tablet in beagle dogs.

  20. Errors in veterinary practice: preliminary lessons for building better veterinary teams.

    Science.gov (United States)

    Kinnison, T; Guile, D; May, S A

    2015-11-14

    Case studies in two typical UK veterinary practices were undertaken to explore teamwork, including interprofessional working. Each study involved one week of whole team observation based on practice locations (reception, operating theatre), one week of shadowing six focus individuals (veterinary surgeons, veterinary nurses and administrators) and a final week consisting of semistructured interviews regarding teamwork. Errors emerged as a finding of the study. The definition of errors was inclusive, pertaining to inputs or omitted actions with potential adverse outcomes for patients, clients or the practice. The 40 identified instances could be grouped into clinical errors (dosing/drugs, surgical preparation, lack of follow-up), lost item errors, and most frequently, communication errors (records, procedures, missing face-to-face communication, mistakes within face-to-face communication). The qualitative nature of the study allowed the underlying cause of the errors to be explored. In addition to some individual mistakes, system faults were identified as a major cause of errors. Observed examples and interviews demonstrated several challenges to interprofessional teamworking which may cause errors, including: lack of time, part-time staff leading to frequent handovers, branch differences and individual veterinary surgeon work preferences. Lessons are drawn for building better veterinary teams and implications for Disciplinary Proceedings considered. British Veterinary Association.

  1. Performance properties of the population bioequivalence approach for in vitro delivered dose for orally inhaled respiratory products.

    Science.gov (United States)

    Morgan, Beth; Strickland, Helen

    2014-01-01

    Regulatory agencies, industry, and academia have acknowledged that in vitro assessments serve a role in establishing bioequivalence for second-entry drug product approvals as well as innovator post-approval drug product changes. For orally inhaled respiratory products (OIPs), the issues of correctly analyzing in vitro data and interpreting the results within the broader context of therapeutic equivalence have garnered significant attention. One of the recommended statistical tests for in vitro data is the population bioequivalence method (PBE). The current literature for assessing the PBE statistical approach for in vitro data assumes a log normal distribution. This paper focuses on an assessment of that assumption for in vitro delivered dose. Concepts in development of a statistical model are presented. The PBE criterion and hypotheses are written for the case when data follows a normal distribution, rather than log normal. Results of a simulation study are reported, characterizing the performance of the PBE approach when data are expected to be normally distributed, rather than log normal. In these cases, decisions using the PBE approach are not consistent for the same absolute mean difference that the test product is from the reference product. A conclusion of inequivalency will occur more often if the test product dose is lower than the reference product for the same deviation from target. These features suggest that more research is needed for statistical equivalency approaches for in vitro data.

  2. Veterinary Forensic Toxicology.

    Science.gov (United States)

    Gwaltney-Brant, S M

    2016-09-01

    Veterinary pathologists working in diagnostic laboratories are sometimes presented with cases involving animal poisonings that become the object of criminal or civil litigation. Forensic veterinary toxicology cases can include cases involving animal cruelty (malicious poisoning), regulatory issues (eg, contamination of the food supply), insurance litigation, or poisoning of wildlife. An understanding of the appropriate approach to these types of cases, including proper sample collection, handling, and transport, is essential so that chain of custody rules are followed and proper samples are obtained for toxicological analysis. Consultation with veterinary toxicologists at the diagnostic laboratory that will be processing the samples before, during, and after the forensic necropsy can help to ensure that the analytical tests performed are appropriate for the circumstances and findings surrounding the individual case. © The Author(s) 2016.

  3. Integrative veterinary medical education and consensus guidelines ...

    African Journals Online (AJOL)

    ... and incorporate evidence-based medicine in clinical practice with all therapies, including those presently regarded as integrative, complementary, or alternative. Keywords: Complementary and alternative veterinary medicine, Integrative veterinary course, Integrative veterinary curriculum, Integrative veterinary medicine, ...

  4. Random-effects linear modeling and sample size tables for two special crossover designs of average bioequivalence studies: the four-period, two-sequence, two-formulation and six-period, three-sequence, three-formulation designs.

    Science.gov (United States)

    Diaz, Francisco J; Berg, Michel J; Krebill, Ron; Welty, Timothy; Gidal, Barry E; Alloway, Rita; Privitera, Michael

    2013-12-01

    Due to concern and debate in the epilepsy medical community and to the current interest of the US Food and Drug Administration (FDA) in revising approaches to the approval of generic drugs, the FDA is currently supporting ongoing bioequivalence studies of antiepileptic drugs, the EQUIGEN studies. During the design of these crossover studies, the researchers could not find commercial or non-commercial statistical software that quickly allowed computation of sample sizes for their designs, particularly software implementing the FDA requirement of using random-effects linear models for the analyses of bioequivalence studies. This article presents tables for sample-size evaluations of average bioequivalence studies based on the two crossover designs used in the EQUIGEN studies: the four-period, two-sequence, two-formulation design, and the six-period, three-sequence, three-formulation design. Sample-size computations assume that random-effects linear models are used in bioequivalence analyses with crossover designs. Random-effects linear models have been traditionally viewed by many pharmacologists and clinical researchers as just mathematical devices to analyze repeated-measures data. In contrast, a modern view of these models attributes an important mathematical role in theoretical formulations in personalized medicine to them, because these models not only have parameters that represent average patients, but also have parameters that represent individual patients. Moreover, the notation and language of random-effects linear models have evolved over the years. Thus, another goal of this article is to provide a presentation of the statistical modeling of data from bioequivalence studies that highlights the modern view of these models, with special emphasis on power analyses and sample-size computations.

  5. Pharmacokinetic and bioequivalence study of itopride HCl in healthy volunteers.

    Science.gov (United States)

    Cho, Kyung-Jin; Cho, Wonkyung; Cha, Kwang-Ho; Park, Junsung; Kim, Min-Soo; Kim, Jeong-Soo; Hwang, Sung-Joo

    2010-01-01

    In the present study two different formulations containing 50 mg itopride HCl (N-[4-12-(dimethylamino)ethoxylbenzyl]-3,4-dimethoxybenzamide HCl, CAS 122898-67-3) were compared in 28 healthy male volunteers in order to compare the bioavailability and prove the bioequivalence. The study was performed in an open, single dose randomized, 2-sequence, crossover design in 28 healthy male volunteers with a one-week washout period. Blood samples for pharmacokinetic profiling were drawn at selected times during 24 h. The serum concentrations of itopride HCl were determined using a specific and sensitive HPLC method with fluorescence detection. The detection limit of itopride HCl was 5 ng/ml and no endogenous compounds were found to interfere with analysis. The mean AUC(0-4h), AUC(0 --> infinity), C(max), T(max) and T1/2 were 865.28 ng x h/ml, 873.04 ng x h/ml, 303.72 ng/ml, 0.75 h, and 2.95 h, respectively, for the test formulations, and 833.00 ng x h/ml, 830.97 ng x h/ml, 268.01 ng/ml, 0.78 h, and 2.83 h, respectively, for the reference formulation. Both primary target parameters AUC(0 --> infinity) and C(max) were log-transformed and tested parametrically by analysis of variance (ANOVA). 90% confidence intervals of AUC(0 --> infinity) and C(max) were 100.57%-109.56% and 105.46%-121.18%, respectively, and were in the range of acceptable limits of bioequivalence (80-125%). Based on these results, the two formulations of itopride HCl are considered to be bioequivalent.

  6. Drug: D08455 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available as: C18605 ... veterinary medicine Juvenile hormone mimic Larval growth inhibitor ... CAS: 95737-68-1 PubChem: ... D08455 Drug Pyriproxyfen; Cyclio [veterinary] (TN) ... C20H19NO3 D08455.gif ... Same

  7. Drug: D07613 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D07613 Drug Carbaryl (BAN); Carbaril; Flea and tick powder [veterinary] (TN) ... C12H...11NO2 D07613.gif ... Same as: C07491 ... carbamate insecticide cholinesterase inhibitor veterinary medicine ...

  8. Drug: D08251 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D08251 Drug Nandrolone laurate; Nandrolone dodecanoate; Laurabolin [veterinary] (T...14AB01 S01XA11 Chemical group: DG00142 ... Estren derivative veterinary medicine NR3C4 (AR) [HSA:367] [KO:K085

  9. Drug: D08251 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D08251 Drug Nandrolone laurate; Nandrolone dodecanoate; Laurabolin [veterinary] (TN...) C30H48O3 456.3603 456.7003 D08251.gif Anabolic ATC code: A14AB01 anabolic steroids veterinary medicine and

  10. Sokoto Journal of Veterinary Sciences

    African Journals Online (AJOL)

    um chafe

    191-203. FACULTY OF VETERINARY MEDICINE. USMANU DANFODIYO UNIVERSITY. P.M.B. 2346, SOKOTO. NIGERIA. Sokoto Journal of Veterinary Sciences. ISSN 1595-093X. Nwanta et al. /Sokoto Journal of Veterinary Sciences (2008). 7(2): 42-45. Field trial of Malaysian thermostable Newcastle disease vaccine in.

  11. African Journals Online: Veterinary Science

    African Journals Online (AJOL)

    Items 1 - 15 of 15 ... ... of the Kenya Veterinary Association. It publishes original papers in English, within the whole field of animal science and veterinary medicine and those addressing legal and policy issues related to the veterinary profession. The journal accepts articles and reports in the areas of Anatomy and Histology, ...

  12. The ABCG2 Efflux Transporter in the Mammary Gland Mediates Veterinary Drug Secretion across the Blood-Milk Barrier into Milk of Dairy Cows.

    Science.gov (United States)

    Mahnke, Hanna; Ballent, Mariana; Baumann, Sven; Imperiale, Fernanda; von Bergen, Martin; Lanusse, Carlos; Lifschitz, Adrian L; Honscha, Walther; Halwachs, Sandra

    2016-05-01

    In human and mice ATP-binding cassette efflux transporter ABCG2 represents the main route for active drug transport into milk. However, there is no detailed information on the role of ABCG2 in drug secretion and accumulation in milk of dairy animals. We therefore examined ABCG2-mediated drug transport in the bovine mammary gland by parallel pharmacokinetic studies in lactating Jersey cows and in vitro flux studies using the anthelmintic drug monepantel (MNP) as representative bovine ABCG2 (bABCG2) drug substrate. Animals received MNP (Zolvix, Novartis Animal Health Inc.) once (2.5 mg/kg per os) and the concentrations of MNP and the active MNP metabolite MNPSO2 were assessed by high-performance liquid chromatography. Compared with the parent drug MNP, we detected higher MNPSO2 plasma concentrations (expressed as area under the concentration-versus-time curve). Moreover, we observed MNPSO2 excretion into milk of dairy cows with a high milk-to-plasma ratio of 6.75. In mechanistic flux assays, we determined a preferential time-dependent basolateral-to-apical (B > A) MNPSO2 transport across polarized Madin-Darby canine kidney II cells-bABCG2 monolayers using liquid chromatography coupled with tandem mass spectrometry analysis. The B > A MNPSO2 transport was significantly inhibited by the ABCG2 inhibitor fumitremorgin C in bABCG2- but not in mock-transduced MDCKII cells. Additionally, the antibiotic drug enrofloxacin, the benzimidazole anthelmintic oxfendazole and the macrocyclic lactone anthelmintic moxidectin caused a reduction in the MNPSO2(B > A) net efflux. Altogether, this study indicated that therapeutically relevant drugs like the anthelmintic MNP represent substrates of the bovine mammary ABCG2 transporter and may thereby be actively concentrated in dairy milk. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  13. HOMEOPATHY IN VETERINARY MEDICINE

    Directory of Open Access Journals (Sweden)

    Jelena Šuran

    2012-07-01

    Full Text Available Homeopathy is an alternative medicine practice, which has been used for the past 200 years but, until now, scientific methods have not proven its effectiveness. The use of highly diluted natural substances based on the principal that similar heals similar is contrary to the scientific theories of the conventional medicine. In veterinary medicine homeopathic remedies are most frequently used for chronic conditions of small animals, but also their application in organic farming is increasing. Minimal number of clinical studies about the use of homeopathy in veterinary medicine has been published in scientific literature. The results of effectiveness are contradictory, which can be explained by being a consequence of different research methodologies. However, there is a significant inverse proportionality between the quality of research and results that approve of the use of homeopathy. In evidence based veterinary medicine scientific approach is fundamental for objective diagnostics and treatment prescription, and homeopathy is an excellent teaching model for possible methodological failures in scientific research. Key words: homeopathy, alternative medicine, evidence based veterinary medicine

  14. NIGERIAN VETERINARY JOURNAL

    African Journals Online (AJOL)

    ADEYEYE

    1Department of Veterinary Surgery and Radiology, Ahmadu Bello University Zaria; 2Department of Animal Health .... and Tucker, 2004). Even for animals for which direct observation of intraocular structures is possible, ultrasonography may be helpful for tumor identification, ..... determination of the size of eye prosthesis in.

  15. ,3. Nigerian Veterinary Journal

    African Journals Online (AJOL)

    Nigerian Veterinary Journal. Vol 34 pi res-sea. Epizootiologicul Survey of Bovine Brucellosis in. Nomadic Pastoral ... brucellosis in the pastoral herds of Niger State despite its high cattle population and no research has ..... Brucella abortus infection in Cattle in Chile. Archivos de Med.Veterin.. 27: 45-50. ROTH, F., ZINSSTAG ...

  16. Veterinary Replicon Vaccines

    NARCIS (Netherlands)

    Hikke, Mia C.; Pijlman, Gorben P.

    2017-01-01

    Vaccination is essential in livestock farming and in companion animal ownership. Nucleic acid vaccines based on DNA or RNA provide an elegant alternative to those classical veterinary vaccines that have performed suboptimally. Recent advances in terms of rational design, safety, and efficacy have

  17. . Nigerian Veterinary Journal

    African Journals Online (AJOL)

    leptospirosis. Case report. An 1 1 year old male Alsatian dog was presented to the Veterinary Teaching Hospital of the. University of lbadan (VTH-Ul) with a hist01y of anorexia, weakness and exercise intolerance of5 days duration. On clinical examination, the rectal temperature was normal andlung auscultation revealed a ...

  18. Zimbabwe Veterinary Journal

    African Journals Online (AJOL)

    Journal Homepage Image. Zimbabwe Veterinary Journal contains original and review papers on all aspects of animal health in Zimbabwe and SADC countries, including articles by non-veterinarians. This journal did not publish any issues between 2002 and 2015 but has been revived and and it actively accepting papers ...

  19. NIGERIAN VETERINARY JOURNAL

    African Journals Online (AJOL)

    ADEYEYE

    according to International guiding principles for biochemical research involving animals. (C. I .O. M .S .1985). Source of Trypanosomes. Trypanosoma brucei brucei (Federe strain) used for the study was obtained from donor rats maintained at the postgraduate laboratory of the Department of Veterinary. Microbiology and ...

  20. '*Nigerian Veterinary Journal

    African Journals Online (AJOL)

    '*Nigerian Veterinary Journal. ~. Vol35 (1)9~8· 955. ARTICLE. Prevalence of Aeromonas hydrophila. Isolates in cultured and Feral Clarias gariepinus of the Kainji Lake Area, Nigeria,. OMEJE, V.O.' and CHUKWU, C.C.. Aquaculture Programme. National Institute for Freshwater Fisheries Researcl1. PMB 6006, New Bussa, ...

  1. NIGERIAN VETERINARY JOURNAL

    African Journals Online (AJOL)

    ADEYEYE

    Although the safety profile of short term dexamethasone treatment has been established, there has been ... Although low-dose dexamethasone treatment has been used in veterinary and human clinics for many years and produced no severe ..... in women with polycystic ovarian syndrome (PcOS) (Keay et al., 2001).

  2. 50 Years: Veterinary Medicine.

    Science.gov (United States)

    Narlesky, Lynn

    1998-01-01

    Describes the history, research, teaching strategies, and specialties of the University of California at Davis School of Veterinary Medicine. Documents effects of changing societal attitudes toward wildlife, pets, working animals, and food animals on curriculum, the systems approach to disease, comparative genetics, biotechnology, the ecology of…

  3. NIGERIAN VETERINARY JOURNAL

    African Journals Online (AJOL)

    ADEYEYE

    prevalence of diseases and available veterinary services were noticed to be present in these communities. The draught animal survival ability rather ... labour in farming and transportation. (Chantalakhana and Bunyavejehewin, 1994) ..... spreading of these diseases such as. Babesiosis and Anaplasmosis to these animals.

  4. g Nigerian Veterinary Journal

    African Journals Online (AJOL)

    ovemight in a cool box. Serum was extracted using a plastic micropipette and transferred into sample bottles and was frozen until tested. Detection of antibodies to N DV. Antigen. Newcastle disease virus LaSota strain obtained from the National Veterinary Research Institute. (NVRI), Vom, was used as antigen for HI-test.

  5. NIGERIAN VETERINARY JOURNAL

    African Journals Online (AJOL)

    ADEYEYE

    Vet. J., March 2017. Vol 38 (1): 57-68. ORIGINAL ARTICLE. An Audit of Castration of Male Dogs in Enugu Metropolis, South. Eastern Nigeria. Raheem, K. A.. 1Department of Veterinary ..... The internal genital organs like the prostate gland, urethra, penis, bulbis ... As biotechnology and medicine continue to advance, other ...

  6. NIGERIAN VETERINARY JOURNAL

    African Journals Online (AJOL)

    ADEYEYE

    Vet. J., June 2016. Vol. 37 (2): 82-87. ORIGINAL ARTICLE. Cystographic Evaluation Post Colocystoplasty in Two Nigerian. Indigenous Dogs. Muhammad S. T.*. 1 ., Awasum C. A.. 2 ... integrity/morphology of most internal body organs or system(s) of an individual, ..... Journal of Veterinary. Medicine and Animal Health, 7(1):.

  7. Nigerian Veterinary Journal

    African Journals Online (AJOL)

    En-Joy

    Lungworms of Small Ruminants Slaughtered in Restaurants of Ambo, Oromia Regional State, Ethiopia. 1. 1. 1. 2. GAROMSSA, T. , BERSISSA, K. , DINKA, A.* and ENDRIAS, Z. 1. 2. School of Veterinary Medicine, Addis Ababa University. Ambo University. *Corresponding author: dinka_ayana@yahoo.com. INTRODUCTION.

  8. NIGERIAN VETERINARY JOURNAL

    African Journals Online (AJOL)

    ADEYEYE

    NIGERIAN VETERINARY JOURNAL. ISSN 0331-3026. Nig. Vet. J., March 2016. Vol. 37 (1): 24-31. ORIGINAL ARTICLE. Occurrence of Klebsiella Species in Cultured African Catfish in Oyo. State, South-West Nigeria. Adeshina, I. 1. *; Abdrahman, S. A.. 2 and Yusuf, A. A.. 3. 1Department of Aquaculture and Fisheries, ...

  9. Nigerian Veterinary Journal

    African Journals Online (AJOL)

    SUMMARY. An audit of surgical antibiotic prophylaxis at the Veterinary Teaching Hospital, lbadan between 2008 and 2011 was conducted to evaluate the level of compliance with standard practices. The study involved retrospective case note audit of surgical procedures performed during the period. A total number of 108.

  10. A randomized two-way crossover bioequivalence study in healthy adult volunteers of paediatric zidovudine/lamivudine/nevirapine fast-disintegrating fixed-dose combination tablet.

    Science.gov (United States)

    Joshi, Anjali; Gbadero, Daniel; Esseku, Fredrick; Adesanya, Olufikayo J; Adeyeye, Moji C

    2017-04-01

    The bioequivalence study was conducted to compare the developed paediatric fixed-dose combination (FDC) zidovudine/lamivudine/nevirapine (60/30/50 mg) tablet - the test formulation - with the combined mixture of single-entity innovator products (reference product). A single-dose open-label randomized two-way crossover study was conducted in healthy adult African volunteers after an informed consent was obtained. The 24 volunteers, divided into two groups, were administered the products after an overnight fast on two treatment days with 14 days of washout period. Blood samples were collected for 96 h and analysed using a validated RP-HPLC-UV assay method. Pharmacokinetic (PK) parameters (non-compartmental model) were assessed with WinNonlin® software. Analysis of variance (ANOVA) and FDA bioequivalence statistical criterion of 90% CI or 80% to 125% range (set at P 0.05). The 90% CIs for all the drugs were within the 80% to 125% range. The developed FDC tablet is bioequivalent to the reference product. © 2016 Royal Pharmaceutical Society.

  11. Common questions in veterinary toxicology.

    Science.gov (United States)

    Bates, N; Rawson-Harris, P; Edwards, N

    2015-05-01

    Toxicology is a vast subject. Animals are exposed to numerous drugs, household products, plants, chemicals, pesticides and venomous animals. In addition to the individual toxicity of the various potential poisons, there is also the question of individual response and, more importantly, of species differences in toxicity. This review serves to address some of the common questions asked when dealing with animals with possible poisoning, providing evidence where available. The role of emetics, activated charcoal and lipid infusion in the management of poisoning in animals, the toxic dose of chocolate, grapes and dried fruit in dogs, the use of antidotes in paracetamol poisoning, timing of antidotal therapy in ethylene glycol toxicosis and whether lilies are toxic to dogs are discussed. © 2015 British Small Animal Veterinary Association.

  12. Veterinary pharmacovigilance in India: A need of hour.

    Science.gov (United States)

    Kumar, Rishi; Kalaiselvan, Vivekanandan; Verma, Ravendra; Kaur, Ismeet; Kumar, Pranay; Singh, G N

    2017-01-01

    Veterinary pharmacovigilance (PV) is important for the Medicine which are used for treating disease in animals. It becomes more important when these animals are further used for producing food. Adverse drug reactions (ADRs) have a direct impact on animals and indirect impact on human beings, for example, through milk products, other animal producing food products. Currently, PV program of India is playing a vital role in assessing the safety of medicines in Indian Population. The safety of medicine in animals can be assessed by veterinary PV. The research institutes involved in animal research and veterinary hospitals can be considered as ADR monitoring centers to assess the safety of medicines on animals.

  13. Bioequivalence evaluation of two formulations of pidotimod using a limited sampling strategy.

    Science.gov (United States)

    Huang, Ji-Han; Huang, Xiao-Hui; Wang, Kun; Li, Jian-Chun; Xie, Xue-Feng; Shen, Chen-Lin; Li, Lu-Jin; Zheng, Qing-Shan

    2013-07-01

    The aim of this study was to develop a limited sampling strategy (LSS) to assess the bioequivalence of two formulations of pidotimod. A randomized, two-way, cross-over study was conducted in healthy Chinese volunteers to compare two formulations of pidotimod. A limited sampling model was established using regression models to estimate the pharmacokinetic parameters and assess the bioequivalence of pidotimod. The model was internally validated by the Jack-knife method and graphical methods. The traditional non-compartmental method was also used to analyze the data and compared with LSS method. The results indicate that following oral administration of a single 800 mg dose, the plasma AUC(0-12 h) and C(max) of pidotimod can be predicted accurately using only two to four plasma samples. The bioequivalence assessment based on the LSS models provided results very similar to that obtained using all the observed concentration-time data points and indicate that the two pidotimod formulations were bioequivalent. A LSS method for assessing the bioequivalence of pidotimod formulations was established and proved to be applicable and accurate. This LSS method could be considered appropriate for a pidotimod bioequivalence study, providing an inexpensive cost of sampling acquisition and analysis. And the methodology presented here may also be applicable to bioequivalence evaluation of other medications. Crown Copyright © 2013. Published by Elsevier Masson SAS. All rights reserved.

  14. [Generics: similarities, bioequivalence but no conformity].

    Science.gov (United States)

    Even-Adin, D; De Muylder, J A; Sternon, J

    2002-01-01

    The using of generic forms (GF) is presented as a potential source of budgetary "saving of money" in the field of pharmaceutical expenses. Not frequently prescribed in Belgium, they win a new interest thanks to the recent making use of the "reference repayment". Sale's authorization of GF is controlled by european rules, but some questions about their identity to original medications remain. Do similarities based only upon qualitative and quantitative composition in active molecules, pharmaceutical forms and biodisponibility give us all requested guaranties? Several cases of discordances can appear; the major elements of non conformity are the nature of excipients, notice's contents and the value of biodisponibility studies. However, in term of economy, in the drug market, development of GF appears to constitute an unavoidable phenomenon.

  15. [Generics: essentially similar, bioequivalent but not identical].

    Science.gov (United States)

    Even-Adin, D; De Muylder, J A; Sternon, J

    2001-12-01

    The using of generic forms (GF) is presented as a potential source of budgetary "saving of money" in the field of pharmaceutical expenses. Not frequently prescribed in Belgium, they win a new interest thanks to the recent making use of the "reference repayment". Sale's authorization of GF is controlled by european rules, but some questions about their identity to original medications remain. Do similarities based only upon qualitative and quantitative composition in active molecules, pharmaceutical forms and biodisponibility give us all requested guarantees? Several cases of discordances can appear: the major elements of non conformity are the nature of excipients, notice's contents and the value of biodisponibility studies. However, in term of economy, in the drug market, development of GF appears to constitute an unavoidable phenomenon.

  16. Bioequivalence evaluation of two roxithromycin formulations in healthy human volunteers by high performance liquid cromatography coupled to tandem mass spectrometry.

    Science.gov (United States)

    Motta, M; Ribeiro, W; Ifa, D R; Moares, M E; Moraes, M O; Corrado, A P; De Nucci, G

    1999-01-01

    The bioequivalence of two different formulations containing roxithromycin (SPE-712-1). Oral suspension 300 mg/15 mL as test formulation and Rotram, tablets 300 mg as reference formulation, both by Schering Plough S.A., Brazil) was evaluated in 24 healthy volunteers of both sexes (12 male and 12 female). The study was conducted open with randomized two-period crossover design and a 14-day washout period. Each subject received 300 mg of each roxithromycin formulation. Plasma samples were obtained over a 72-hour interval and roxithromycin concentrations were analyzed by combined LC-MS/MS with positive ion electrospray ionization using selected ion monitoring method. From the plasma roxithromycin concentration vs time curves the following pharmacokinetic parameters were obtained: AUC(0-72 h), AUC(0-infinity), Cmax, t1/2 ratios and tmax individual differences. The 90% for confidence interval (CI) of geometric mean SPE-712-L/Rotram individual percent ratio were 105.0-128.3% for AUC(0-72 h), and 78.4-96.9 for Cmax. Although this 90% CI were marginally outside the interval proposed by the Food and Drug Administration, the probability assessed by the two-one sided West for ratios was included in the 0.8-1.25 interval, as we concluded that SPE-712-L oral suspension formulation was bioequivalent to Rotram tablet formulation for the extent and rate of absorption.

  17. A Novel Approach to Testing for Average Bioequivalence Based on Modeling the Within-Period Dependence Structure.

    Science.gov (United States)

    Chandrasekhar, Rameela; Shi, Yi; Hutson, Alan D; Wilding, Gregory E

    2015-01-01

    Bioequivalence trials are commonly conducted to assess therapeutic equivalence between a generic and an innovator brand formulations. In such trials, drug concentrations are obtained repeatedly over time and are summarized using a metric such as the area under the concentration vs. time curve (AUC) for each subject. The usual practice is to then conduct two one-sided tests using these areas to evaluate for average bioequivalence. A major disadvantage of this approach is the loss of information encountered when ignoring the correlation structure between repeated measurements in the computation of areas. In this article, we propose a general linear model approach that incorporates the within-subject covariance structure for making inferences on mean areas. The model-based method can be seen to arise naturally from the reparameterization of the AUC as a linear combination of outcome means. We investigate and compare the inferential properties of our proposed method with the traditional two one-sided tests approach using Monte Carlo simulation studies. We also examine the properties of the method in the event of missing data. Simulations show that the proposed approach is a cost-effective, viable alternative to the traditional method with superior inferential properties. Inferential advantages are particularly apparent in the presence of missing data. To illustrate our approach, a real working example from an asthma study is utilized.

  18. New directions for veterinary technology.

    Science.gov (United States)

    Chadderdon, Linda M; Lloyd, James W; Pazak, Helene E

    2014-01-01

    Veterinary technology has generally established itself well in companion-animal and mixed-animal veterinary medical practice, but the career's growth trajectory is uncertain. Michigan State University (MSU) convened a national conference, "Creating the Future of Veterinary Technology-A National Dialogue," in November 2011 to explore ways to elevate the veterinary technician/technologist's role in the veterinary medical profession and to identify new directions in which the career could expand. Veterinary technicians/technologists might advance their place in private practice by not only improving their clinical skills, but by also focusing on areas such as practice management, leadership training, business training, conflict resolution, information technology, and marketing/communications. Some new employment settings for veterinary technicians/technologists include more participation within laboratory animal medicine and research, the rural farm industry, regulatory medicine, and shelter medicine. Achieving these ends would call for new training options beyond the current 2-year and 4-year degree programs. Participants suggested specialty training programs, hybrid programs of various types, online programs, veterinary technician residency programs of 12-18 months, and more integration of veterinary technician/technology students and veterinary medicine students at colleges of veterinary medicine.

  19. Global Harmonization of Comparator Products for Bioequivalence Studies.

    Science.gov (United States)

    Gwaza, Luther; Gordon, John; Leufkens, Hubert; Stahl, Matthias; García-Arieta, Alfredo

    2017-05-01

    Comparator products should be the products that were shown to be safe and efficacious in pivotal clinical trials to ensure prescribability of generics. The use of a common comparator ensures switchability between generics. The selection of the comparator is a national responsibility and may be different between countries. This paper discusses the current recommendations on selection of comparators, the associated problems, and the possibility of harmonization. Most countries follow the World Health Organization (WHO) recommendations for selecting comparator products and require the comparator product to be obtained from their national markets to ensure switchability between the local comparator and their generics. These recommendations are only feasible in the few countries where the repetition of the bioequivalence study is economically feasible, but they are impracticable in all other countries. Furthermore, the exclusive use of the local comparator to ensure switchability is ethically and scientifically questionable. The innovator product from well-regulated markets should be the global comparator. This harmonization is feasible as the concept already applies in the WHO prequalification program. It is ineffectual to harmonize only the requirements for performing bioequivalence studies, if such a study has to be repeated for every single country simply because of the different comparator products.

  20. Bioequivalence Demonstration for Ω-3 Acid Ethyl Ester Formulations: Rationale for Modification of Current Guidance.

    Science.gov (United States)

    Maki, Kevin C; Johns, Colleen; Harris, William S; Puder, Mark; Freedman, Steven D; Thorsteinsson, Thorsteinn; Daak, Ahmed; Rabinowicz, Adrian L; Sancilio, Frederick D

    2017-03-01

    The US Food and Drug Administration (FDA) draft guidance for establishing bioequivalence (BE) of ω-3 acid ethyl esters (containing both eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA] as ethyl esters), used to treat severe hypertriglyceridemia, recommends the conduct of 2 studies: one with participants in the fasting state and one with participants in the fed state. For the fasting study, the primary measures of BE are baseline-adjusted EPA and DHA levels in total plasma lipids. For the fed study, the primary measures of BE are EPA and DHA ethyl esters in plasma. This guidance differs from that established for icosapent ethyl (EPA ethyl esters) in which the primary measure of BE is baseline-adjusted total EPA in plasma lipids for both the fasting and fed states. The FDA guidance for ω-3 acid ethyl esters is not supported by their physiologic characteristics and triglyceride-lowering mechanisms because EPA and DHA ethyl esters are best characterized as pro-drugs. This article presents an argument for amending the FDA draft guidance for ω-3 acid ethyl esters to use baseline-adjusted EPA and DHA in total plasma lipids as the primary measures of BE for both fasting and fed conditions. This change would harmonize the approaches for demonstration of BE for ω-3 acid ethyl esters and icosapent ethyl (EPA ethyl esters) products for future development programs and is the most physiologically rational approach to BE testing. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

  1. Allergens in veterinary medicine.

    Science.gov (United States)

    Mueller, R S; Janda, J; Jensen-Jarolim, E; Rhyner, C; Marti, E

    2016-01-01

    Allergic diseases in animals are increasingly gaining importance in veterinary practice and as research models. For intradermal testing and allergen immunotherapy, a good knowledge of relevant allergens for the individual species is of great importance. Currently, the knowledge about relevant veterinary allergens is based on sensitization rates identified by intradermal testing or serum testing for allergen-specific IgE; crude extracts are the basis for most evaluations. Only a few studies provide evidence about the molecular structure of (particularly) dust mite, insect and mould allergens in dogs and horses, respectively. In those species, some major allergens differ from those in humans. This position paper summarizes the current knowledge about relevant allergens in dogs, cats and horses. © 2015 The Authors Allergy Published by John Wiley & Sons Ltd.

  2. Laser In Veterinary Medicine

    Science.gov (United States)

    Newman, Carlton; Jaggar, David H.

    1982-12-01

    Lasers have been used for some time now on animals for experimental purposes prior to their use in human medical and surgical fields. However the use of lasers in veterinary medicine and surgery per se is a recent development. We describe the application of high and low intensity laser technology in a general overview of the current uses, some limitations to its use and future needs for future inquiry and development.

  3. Veterinary critical care.

    Science.gov (United States)

    Corley, Kevin T T; Mathews, Karol; Drobatz, Kenneth J; Bain, Fairfield T; Hughes, Dez

    2003-04-01

    Veterinary species experience similar perturbations of their health to those of human patients. When the long-term prognosis is good and providing suffering can be minimized, animals stand to benefit greatly from recent advances in the field of emergency and critical care. Outcomes in many conditions in small and large animals have improved markedly in the last 15 years, as management has improved, making the financial and emotional investment in critical care worthwhile for many owners.

  4. Radiation protection for veterinary practices

    Energy Technology Data Exchange (ETDEWEB)

    Wheelton, R.; McCaffery, A. (National Radiological Protection Board, Glasgow (United Kingdom). Scottish Centre)

    1993-01-01

    This brief article discusses radiation protection for diagnostic radiography in veterinary practices. It includes aspects such as a radiation protection adviser, personal dosimetry but in particular a Veterinary Monitoring Service, developed by the NRPB, which offers veterinary practitioners the convenience of making simple but essential measurements for themselves using photographic films contained in a 'vet pack' to determine the operating condition of their X-ray machine. (U.K.).

  5. How is veterinary parasitology taught in China?

    Science.gov (United States)

    Huang, Wei-Yi; Wang, Ming; Suo, Xun; Lun, Zhao-Rong; Zhu, Xing-Quan

    2006-12-01

    Many parasites of domestic animals in China are of major socioeconomic and medical importance. Hence, veterinary parasitology is one of the core subjects for undergraduate and postgraduate students of veterinary science. Here, we review the teaching of veterinary parasitology in Chinese universities, including a description of the veterinary science curricula and measures to improve the quality of veterinary parasitology teaching in China.

  6. The Flint Animal Cancer Center (FACC) Canine Tumour Cell Line Panel: a resource for veterinary drug discovery, comparative oncology and translational medicine.

    Science.gov (United States)

    Fowles, J S; Dailey, D D; Gustafson, D L; Thamm, D H; Duval, D L

    2017-06-01

    Mammalian cell tissue culture has been a critical tool leading to our current understanding of cancer including many aspects of cellular transformation, growth and response to therapies. The current use of large panels of cell lines with associated phenotypic and genotypic information now allows for informatics approaches and in silico screens to rapidly test hypotheses based on simple as well as complex relationships. Current cell line panels with large amounts of associated drug sensitivity and genomics data are comprised of human cancer cell lines (i.e. NCI60 and GDSC). There is increased recognition of the contribution of canine cancer to comparative cancer research as a spontaneous large animal model with application in basic and translational studies. We have assembled a panel of canine cancer cell lines to facilitate studies in canine cancer and report here phenotypic and genotypic data associated with these cells. © 2016 John Wiley & Sons Ltd.

  7. Drug: D07767 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D07767 Drug Cyromazine (USP/INN); Neporex (TN) C6H10N6 166.0967 166.1838 D07767.gif Insecticide [veterinary...]; Antiparasitic [veterinary] Same as: C14147 veterinary medicine CAS: 66215-27-8 Pu

  8. Drug: D02547 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D02547 Drug Pamaquine; Plasmoquine [veterinary] (TN) C19H29N3O 315.2311 315.4531 D0...2547.gif Antimalarial [veterinary] veterinary medicine map07025 Quinolines CAS: 491-92-9 PubChem: 17396718 L

  9. Veterinary Oncology Immunotherapies.

    Science.gov (United States)

    Bergman, Philip J

    2018-03-01

    The ideal cancer immunotherapy agent should be able to discriminate between cancer and normal cells, be potent enough to kill small or large numbers of tumor cells, and be able to prevent recurrence of the tumor. Tumor immunology and immunotherapy are among the most exciting and rapidly expanding fields; cancer immunotherapy is now recognized as a pillar of treatment alongside traditional modalities. This article highlights approaches that seem to hold particular promise in human clinical trials and many that have been tested in veterinary medicine. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Hirudotherapy in veterinary medicine.

    Science.gov (United States)

    Sobczak, Natalia; Kantyka, Magdalena

    2014-01-01

    The saliva of medicinal leeches, e.g., Hirudo medicinalis and Hirudo verbana commonly used in hirudotherapy, contains more than 100 bioactive substances with various therapeutic effects, including anticoagulant, vasodilator, thrombolytic, anti-inflammatory and anaesthetic properties. Recently, leeches have been used very successfully in veterinary medicine to treat many diseases of animals, especially dogs, cats and horses. The most common indications for the use of leeches are hip and elbow dysplasia, acute and chronic arthritis, diseases associated with inflammation of tendons, ligaments, and fascia, diseases of the vertebrae and the treatment of scars. Leech therapy is a painless procedure which takes an average of 30 to 120 minutes, the time being dependent on the size of the animal. All leeches used in medical procedures should originate only from certified biofarms. The maintenance of sterile conditions for the culture, transport and storage of medical leeches is very important to protect animals from microbial infections. Hirudotherapy is successfully used in veterinary medicine, especially when traditional treatment is not effective, the effects of treatment are too slow, or after surgery, when the tissues may be threatened by venous congestion.

  11. Surgical Lasers In Veterinary Medicine

    Science.gov (United States)

    Newman, H. C.

    1987-03-01

    Veterinary medicine is a latecomer in benefiting from the advent of surgical lasers. It is ironic that although most of the basic work in lasers is carried out in animal species with which we are most conversant, veterinary medicine as a profession has not been very extensively involved.

  12. Veterinary dentistry: a clinician's viewpoint.

    Science.gov (United States)

    Baxter, Colin

    2013-06-01

    This is a clinician's view of the current state of veterinary dentistry at the level of the general practitioner across the different species. An indication of the work done and the hazards commonly encountered are covered. To increase awareness within the dental profession of the current state of veterinary dentistry.

  13. Sokoto Journal of Veterinary Sciences

    African Journals Online (AJOL)

    Journal Homepage Image. The Journal publishes original research articles related to veterinary sciences, including livestock health and production, diseases of wild life and fish, preventive veterinary medicine and zoonoses among others. Case reports, review articles and editorials are also accepted. Other sites related to ...

  14. Sokoto Journal of Veterinary Sciences

    African Journals Online (AJOL)

    um chafe

    1Department of Veterinary Pathology and Microbiology. 2Department of Veterinary Public Health and Preventive Medicine. Ahmadu Bello .... and cresol as its active ingredients. The most common disinfectant reported to be used in the various hatcheries investigated was Morigad® which has phenol as its active ingredient.

  15. Open Veterinary Journal: Editorial Policies

    African Journals Online (AJOL)

    Focus and Scope. Open Veterinary Journal is a peer reviewed international open access online and printed journal that publishes high-quality original research articles, reviews, short communications and case reports dedicated to all aspects of veterinary sciences and its related subjects.

  16. Perspectives on academic veterinary administration.

    Science.gov (United States)

    Gelberg, H B; Gelberg, S

    2001-09-15

    It is important for veterinary administrators to apply knowledge bases from other fields to their own unique administrative needs. For example, although some resources are written for business managers, the discussions of four key management competency areas, guidelines for mastering these skills, organizational assessment tools, and other self-help tools may provide interesting food-for-thought for veterinary administrators.(76) In developing their own administrative styles, administrators should seek to apply those principles that seem to intuitively fit with their personal research styles, work situations, managerial styles, administrative preferences, and unique organizational culture. Through strengthening their liaisons with community and university business programs, counseling agencies, employee assistance programs, and psychology researchers, administrators can continue to be exposed to and benefit from new paradigms for consideration in veterinary medical environments. Through these liaisons, the unique needs of veterinary medical environments are also communicated to individuals within the fields of psychology and business, thus stimulating new research that specifically targets veterinary medical environment leadership issues. Each field has unique contributions to help veterinary administrators work toward creating veterinary medical environments that are creative, energetic, visionary, pragmatic, and highly marketable in order to help administrators recruit and nurture the best and brightest veterinary researchers, teachers, and clinicians.

  17. 76 FR 3488 - Implantation or Injectable Dosage Form New Animal Drugs; Oxytetracycline and Flunixin

    Science.gov (United States)

    2011-01-20

    ... Animal Drugs; Oxytetracycline and Flunixin AGENCY: Food and Drug Administration, HHS. ACTION: Final rule... veterinary prescription use of a combination drug injectable solution containing oxytetracycline and flunixin... that provides for veterinary prescription use of HEXASOL (oxytetracycline and flunixin meglumine...

  18. Assessment of Bioequivalence of Weak Base Formulations Under Various Dosing Conditions Using Physiologically Based Pharmacokinetic Simulations in Virtual Populations. Case Examples: Ketoconazole and Posaconazole.

    Science.gov (United States)

    Cristofoletti, Rodrigo; Patel, Nikunjkumar; Dressman, Jennifer B

    2017-02-01

    Postabsorptive factors which can affect systemic drug exposure are assumed to be dependent on the active pharmaceutical ingredient (API), and thus independent of formulation. In contrast, preabsorptive factors, for example, hypochlorhydria, might affect systemic exposure in both an API and a formulation-dependent way. The aim of this study was to evaluate whether the oral absorption of 2 poorly soluble, weakly basic APIs, ketoconazole (KETO) and posaconazole (POSA), would be equally sensitive to changes in dissolution rate under the following dosing conditions-coadministration with water, with food, with carbonated drinks, and in drug-induced hypochlorhydria. The systems-components of validated absorption and PBPK models for KETO and POSA were modified to simulate the above-mentioned clinical scenarios. Virtual bioequivalence studies were then carried out to investigate whether formulation effects on the plasma profile vary with the dosing conditions. The slow precipitation of KETO upon reaching the upper part of the small intestine renders its absorption more sensitive to the completeness of gastric dissolution and thus to the gastric environment than POSA, which is subject to extensive precipitation in response to a pH shift. The virtual bioequivalence studies showed that hypothetical test and reference formulations containing KETO would be bioequivalent only if the microenvironment in the stomach enables complete gastric dissolution. We conclude that physiologically based pharmacokinetic modeling and simulation has excellent potential to address issues close to bedside such as optimizing dosing conditions. By studying virtual populations adapted to various clinical situations, clinical strategies to reduce therapeutic failures can be identified. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  19. Mental health and the veterinary profession.

    Science.gov (United States)

    Patterson, Ellie

    2017-10-07

    Ellie Patterson, Vetlife marketing officer, summarises the services offered by Vetlife - an independent, confidential and free charity for everyone in the veterinary community. British Veterinary Association.

  20. En Route towards European Clinical breakpoints for veterinary antimicrobial susceptibility testing

    NARCIS (Netherlands)

    Toutain, Pierre Louis; Bousquet-Mélou, Alain; Damborg, Peter; Ferran, Aude A.; Mevius, Dik; Pelligand, Ludovic; Veldman, Kees T.; Lees, Peter

    2017-01-01

    VetCAST is the EUCAST sub-committee for Veterinary Antimicrobial Susceptibility Testing. Its remit is to define clinical breakpoints (CBPs) for antimicrobial drugs (AMDs) used in veterinary medicine in Europe. This position paper outlines the procedures and reviews scientific options to solve

  1. Radiological protection in veterinary practice

    Energy Technology Data Exchange (ETDEWEB)

    Konishi, Emiko; Tabara, Takashi (Tokyo Univ. (Japan). Research Center for Nuclear Engineering and Technology); Kusama, Tomoko

    1990-06-01

    To propose measures for radiological protection of veterinary workers in Japan, X-ray exposure of workers in typical conditions in veterinary clinics was assessed. Dose rates of useful beam and scattered radiation, worker exposure doses at different stations, and effectiveness of protective clothing were determined using TLD and ion chambers. As precausions against radiation, the following practices are important: (1) use of suitable and properly maintained X-ray equipment, (2) proper selection of safe working stations, (3) use of protective clothing. Regulations are necessary to restrict the use of X-rays in the veterinary field. Because the use of X-rays in the veterinary field is not currently controlled by law, the above precautions are essential for minimizing exposure of veterinary staff. (author).

  2. Scientific considerations concerning the EMA change in the definition of "dose" of the BCS-based biowaiver guideline and implications for bioequivalence.

    Science.gov (United States)

    Daousani, Chrysa; Macheras, Panos

    2015-01-30

    This work discusses the scientific aspects of the definition of dose as the 'highest single oral IR dose' recommended for administration in the SmPC (summary of product characteristics) in the current European Medicines Agency (EMA) 2010 Guideline, for the purpose of biopharmaceutics classification system (BCS)-based biowaiver decision making. Analysis of theoretical and experimental data dealing with drug dissolution and biopharmaceutic drug classification reveals that the drug dose is an important parameter for both drug dissolution and biopharmaceutic classification. The relevant implications for the dose considerations in bioequivalence studies are also discussed briefly. It is suggested that the concept of "the highest single dose oral IR dose recommended for administration in the SmPC" of the EMA 2010 Guideline be abolished. It is advisable, each dose strength be considered separately i.e., whether or not it meets the solubility-dissolution regulatory criteria. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Advantage of population pharmacokinetic method for evaluating the bioequivalence and accuracy of parameter estimation of pidotimod.

    Science.gov (United States)

    Huang, Jihan; Li, Mengying; Lv, Yinghua; Yang, Juan; Xu, Ling; Wang, Jingjing; Chen, Junchao; Wang, Kun; He, Yingchun; Zheng, Qingshan

    2016-09-01

    This study was aimed at exploring the accuracy of population pharmacokinetic method in evaluating the bioequivalence of pidotimod with sparse data profiles and whether this method is suitable for bioequivalence evaluation in special populations such as children with fewer samplings. Methods In this single-dose, two-period crossover study, 20 healthy male Chinese volunteers were randomized 1 : 1 to receive either the test or reference formulation, with a 1-week washout before receiving the alternative formulation. Noncompartmental and population compartmental pharmacokinetic analyses were conducted. Simulated data were analyzed to graphically evaluate the model and the pharmacokinetic characteristics of the two pidotimod formulations. Various sparse sampling scenarios were generated from the real bioequivalence clinical trial data and evaluated by population pharmacokinetic method. The 90% confidence intervals (CIs) for AUC0-12h, AUC0-∞, and Cmax were 97.3 - 118.7%, 96.9 - 118.7%, and 95.1 - 109.8%, respectively, within the 80 - 125% range for bioequivalence using noncompartmental analysis. The population compartmental pharmacokinetics of pidotimod were described using a one-compartment model with first-order absorption and lag time. In the comparison of estimations in different dataset, the estimation of random three- andstrategies can provide results similar to those obtained through rich sampling. The nonlinear mixed-effects model requires fewer data points. Moreover, compared with the noncompartmental analysis method, the pharmacokinetic parameters can be more accurately estimated using nonlinear mixed-effects model. The population pharmacokinetic modeling method was used to assess the bioequivalence of two pidotimod formulations with relatively few sampling points and further validated the bioequivalence of the two formulations. This method may provide useful information for regulating bioequivalence evaluation in special populations.

  4. 76 FR 45267 - Determination That INVERSINE (Mecamylamine Hydrochloride) Tablet and Six Other Drug Products Were...

    Science.gov (United States)

    2011-07-28

    ... the approval of duplicate versions of drug products approved under an ANDA procedure. ANDA applicants... drug that was previously approved. ANDA applicants do not have to repeat the extensive clinical testing... ANDA are data to show that the drug that is the subject of the ANDA is bioequivalent to the listed drug...

  5. 77 FR 59403 - Determination That ENDURON (methyclothiazide) Tablets and Six Other Drug Products Were Not...

    Science.gov (United States)

    2012-09-27

    ... duplicate versions of drug products approved under an ANDA procedure. ANDA sponsors must, with certain... necessary to gain approval of a new drug application (NDA). The only clinical data required in an ANDA are data to show that the drug that is the subject of the ANDA is bioequivalent to the listed drug. The...

  6. 76 FR 11488 - Determination That MEGACE (Megestrol Acetate) Tablets and Nine Other Drug Products Were Not...

    Science.gov (United States)

    2011-03-02

    ... the approval of duplicate versions of drug products approved under an ANDA procedure. ANDA applicants... drug that was previously approved. ANDA applicants do not have to repeat the extensive clinical testing... ANDA are data to show that the drug that is the subject of the ANDA is bioequivalent to the listed drug...

  7. 76 FR 59141 - Determination That LOXITANE (Loxapine Succinate) Capsules and Three Other Drug Products Were Not...

    Science.gov (United States)

    2011-09-23

    ... the approval of duplicate versions of drug products approved under an ANDA procedure. ANDA applicants... drug that was previously approved. ANDA applicants do not have to repeat the extensive clinical testing... ANDA are data to show that the drug that is the subject of the ANDA is bioequivalent to the listed drug...

  8. The role of veterinary medicine regulatory agencies.

    Science.gov (United States)

    Smith, M V

    2013-08-01

    An effective animal medicine regulatory programme includes a systematic, evidence-based means of documenting the safety and effectiveness of products before they are produced, marketed or used in a particular country or region. The programme must also include adequate monitoring and controls over the use of these substances. It is clearthat such programmes provide veterinarians, farmers and other animal medicine users with greater assurance that veterinary drugs and biologicals will be safe and effective in preventing and mitigating disease. It is important that these regulatory controls include programmes to ensure that human food obtained from treated animals is safe and that all potential toxicological and microbiological hazards that may be associated with the use of veterinary medicines have been adequately evaluated. There is a great need worldwide for veterinary medicines that provide needed therapies for vast numbers of animals and animal species and, in the case of food-producing animals, for medicinal products that enhance the productivity and efficiency of food production and ensure food safety when they are used in accordance with their approval specifications. The public health mission of regulatory agencies succeeds when they are able to put into the hands of the user an approved, safe and effective, well-manufactured and appropriately labelled medicine, and when there are adequate controls in place to assure proper compliance.

  9. Antiviral chemotherapy in veterinary medicine: current applications and perspectives.

    Science.gov (United States)

    Dal Pozzo, F; Thiry, E

    2014-12-01

    The current situation in the use of antiviral drugs in veterinary medicine is characterised by a novel and optimistic approach.Viruses of veterinary importance are still used as animal models in the developmentof human therapeutics, but there is growing interest in many of these viruses in the identification of antiviral molecules for use in both livestock and companion animals. The use of antiviral drugs in livestock animals is envisaged for the treatment or control of disease on a large scale (mass treatment), whereas in companion animals an individual approach is favoured. An overview of the most recent examples of research in the use of antivirals in veterinary medicine is presented, with particular emphasis on their in vivo applications.

  10. ASVCP quality assurance guidelines: control of general analytical factors in veterinary laboratories.

    Science.gov (United States)

    Flatland, Bente; Freeman, Kathy P; Friedrichs, Kristen R; Vap, Linda M; Getzy, Karen M; Evans, Ellen W; Harr, Kendal E

    2010-09-01

    Owing to lack of governmental regulation of veterinary laboratory performance, veterinarians ideally should demonstrate a commitment to self-monitoring and regulation of laboratory performance from within the profession. In response to member concerns about quality management in veterinary laboratories, the American Society for Veterinary Clinical Pathology (ASVCP) formed a Quality Assurance and Laboratory Standards (QAS) committee in 1996. This committee recently published updated and peer-reviewed Quality Assurance Guidelines on the ASVCP website. The Quality Assurance Guidelines are intended for use by veterinary diagnostic laboratories and veterinary research laboratories that are not covered by the US Food and Drug Administration Good Laboratory Practice standards (Code of Federal Regulations Title 21, Chapter 58). The guidelines have been divided into 3 reports on 1) general analytic factors for veterinary laboratory performance and comparisons, 2) hematology and hemostasis, and 3) clinical chemistry, endocrine assessment, and urinalysis. This report documents recommendations for control of general analytical factors within veterinary clinical laboratories and is based on section 2.1 (Analytical Factors Important In Veterinary Clinical Pathology, General) of the newly revised ASVCP QAS Guidelines. These guidelines are not intended to be all-inclusive; rather, they provide minimum guidelines for quality assurance and quality control for veterinary laboratory testing. It is hoped that these guidelines will provide a basis for laboratories to assess their current practices, determine areas for improvement, and guide continuing professional development and education efforts. ©2010 American Society for Veterinary Clinical Pathology.

  11. Topical safety and vasoconstrictive assay-based bioequivalence of a new reformulated mometasone cream.

    Science.gov (United States)

    Krishna, Rajesh; Horowitz, Ann; Larson, Patrick; Bolognese, James; Marcantonio, Eugene E

    2017-07-01

    A new improved mometasone furoate (Elocon™) cream with an emulsification system that produces a stable emulsion has been developed. In order to register the product in various markets, it was essential to ensure the cream was topically well tolerated and that it was bioequivalent to the reference product. Phase I clinical studies were performed to assess the local safety and tolerability upon multiple dosing of this new cream as well as to assess the single-dose bioequivalence relative to the marketed product. Bioequivalence was assessed using a vasoconstrictive assay (VCA) after a dose-duration pilot study was completed with the marketed Elocon cream. The new mometasone cream and its vehicle were nonirritating in healthy subjects during 21-day patch application (MCII bioequivalence. In the 105 detectors, the ratio (×100%) of AUEC values at ED50 for test vs. standard (90% CI) was 112.91% (105.55, 120.87), within the bioequivalence criteria of (80, 125). These studies supported the registration of reformulated mometasone cream in various markets.

  12. Dental Education in Veterinary Medicine

    Directory of Open Access Journals (Sweden)

    Diana L. Eubanks

    2011-02-01

    Full Text Available Periodontal disease is among the most prevalent canine dis-eases affecting over 75% of dogs. Strengthening of the human-animal bond and the increasing education of the aver-age pet owner, have fostered a heightened awareness of periodontal care in dogs and cats. Industry support has further assisted the small animal veterinarian in providing quality dental treatments and prevention. As recently as the 1990’s, veterinary curriculums contained little or no dental training. That trend is changing as nearly every one of the 28 US Colleges of Veterinary Medicine offers some level of small animal dentistry during the four-year curriculum. Primary areas of focus are on client education, the treatment of periodontal disease, dental prophylaxis, dental radiology, endodontics, exodontics and pain control. Students receive instruction in dental anatomy during their di-dactic curriculum and later experience clinical cases. Graduate DVMs can attend a variety of continuing education courses and even choose to specialize in veterinary dentistry in both small animals and horses. Through the efforts of organizations such as the American Veterinary Dental So-ciety, The American Veterinary Dental College and The Academy of Veterinary Dentistry, many veterinarians have been able to advance their skills in dentistry and improve animal welfare. Increasing ex-pectations of the pet-owning public coupled with the recent advancements of training opportunities available for vete-rinary students, graduate DVMs and certified veterinary technicians make veterinary dentistry an emerging practice-builder among the most successful small animal hospitals.

  13. Bioequivalence and Pharmacokinetic Profiles of Agomelatine 25-mg Tablets in Healthy Chinese Subjects: A Four-Way Replicate Crossover Study Demonstrating High Intra- and Inter-Individual Variations.

    Science.gov (United States)

    Li, Cuiyun; Xu, Jing; Zheng, Yan; Chen, Guiling; Wang, Jianmeng; Ma, Liying; Qiao, Yan; Niu, Junqi; Wu, Min; Zhang, Hong; Li, Xiaojiiao; Chen, Hong; Zhu, Xiaoxue; Liu, Chengjiao; Ding, Yanhua

    2017-06-01

    The present study was designed to assess the bioequivalence of two agomelatine formulations (25-mg tablets) in healthy Chinese male subjects. This single-dose, open-label, randomized, four-way replicate study with a 1-week washout period was conducted in 60 healthy Chinese male volunteers under fasting conditions. Blood samples were collected over a 12-h period after a single dose of the 25-mg agomelatine test (T) formulation or a reference (R) formulation, and the drug concentrations were assayed by liquid chromatography tandem mass spectrometry (LC-MS/MS). Pharmacokinetic parameters were calculated using a non-compartmental model. Bioequivalence between the formulations was assessed. Tolerability and safety were monitored by physical examination, electrocardiogram (12-lead ECG), clinical laboratory tests, and adverse events (AEs). A total of 56 out of 60 subjects completed the study. No AEs were observed. The values of maximum plasma concentration (Cmax), maximum concentration (Tmax), area under curve (AUC)0-t and t1/2 were 12.032 ng/mL, 0.658 h, 12.637 ng·h/mL, and 0.813 h, respectively, for the test formulation, and 10.891 ng/mL, 0.709 h, 11.572 ng·h/mL, and 0.96 h, respectively, for the reference formulation. The intra-individual variability of Cmax and AUC0-t were 78.3 and 61.8%, respectively. The inter-individual coefficients of variance (CVs) of Cmax and AUC0-t were approximately 100%. The 90% confidence intervals for the ratio of means for the log-transformed Cmax (97.7-124.9%), AUC0-t (98.2-118%), and AUC0-∞ (97.8-117.2%) were within the guideline range of bioequivalence (80-125%). The test and reference formulations of agomelatine met the regulatory criteria for bioequivalence of the Chinese Food and Drug Administration. Significant intra-individual and inter-individual variations were found.

  14. [Veterinary dentistry: an update 2008].

    Science.gov (United States)

    van Foreest, Andries

    2008-12-01

    Rooted in human dentistry, veterinary dentistry has developed steadily in the Netherlands since the 1980s and is now recognized as an essential discipline of veterinary medicine. The availability of specialized tools and techniques has led to improved treatment outcomes and results, with the choice of treatment being largely determined by the functionality of the dentition and the costs involved. Domestic animals and horses with dental problems should be referred to dental veterinarians. The Working Group Veterinary Dentistry in the Netherlands is an association for skilled veterinarians with professional dental equipment at their disposal.

  15. The effects of veterinary antibiotics on soil microbial communities

    NARCIS (Netherlands)

    Schmitt, Heike

    2005-01-01

    The possible environmental “side effects” of pharmaceuticals to the environment have not yet been investigated extensively. Among the veterinary drugs, the antibiotics are an important group, due to their extensive use and their potential to also affect environmental bacteria. The main entry path

  16. Adverse reaction to veterinary multivitamins and vitamin B complex ...

    African Journals Online (AJOL)

    It has been reported that dogs in South-western Nigeria react adversely to injectable veterinary multivitamins and human vitamin B complex preparations. Experimentation and interview survey were concurrently conducted to identify the type of Adverse Drug Reactions (ADRs) that the indications produced. For the survey ...

  17. Current Issues and the Veterinary Medical Library

    Science.gov (United States)

    Nault, Andre J.

    2010-01-01

    Veterinary medical libraries and librarians are unique. There are now 33 veterinary colleges in North America, and in accordance with American Veterinary Medical Association accreditation, each has a library managed by an accredited librarian. Colleges with veterinary programs often maintain specialized branch libraries to support the degree,…

  18. Teaching veterinary internal medicine in China.

    Science.gov (United States)

    Li, Jiakui; Guo, Dingzong; Zhou, Donghai; Wu, Xiaoxiong

    2011-01-01

    Veterinary internal medicine (VIM) is a core subject and important clinical discipline for undergraduate students of veterinary science. The present paper reviews current information about the teaching of VIM, presents a description of the veterinary science curriculum, suggests methods to improve the quality of VIM teaching in China, and describes difficulties, problems, and trends in veterinary education in China.

  19. Quantification of cyproheptadine in human plasma by high-performance liquid chromatography coupled to electrospray tandem mass spectrometry in a bioequivalence study.

    Science.gov (United States)

    Mendes, Gustavo Duarte; Arruda, André; Chen, Lu Shi; de Almeida Magalhães, José Cássio; Alkharfy, Khalid M; De Nucci, Gilberto

    2012-01-01

    A rapid, sensitive and specific method to quantify cyproheptadine in human plasma using amitriptyline as the internal standard (IS) is described. The analyte and the IS were extracted from plasma by liquid-liquid extraction using a diethyl-ether/dichloromethane (70/30; v/v) solvent. After removing and drying the organic phase, the extracts were reconstituted with a fixed volume of acetonitrile/water (50/50 v/v)+0.1% of acetic acid. The extracts were analyzed by high performance liquid chromatography coupled to electrospray tandem mass spectrometry (LC-MS/MS). Chromatography was performed isocratically using an Alltech Prevail C18 5 µm analytical column, (150 mm x 4.6 mm I.D.). The method had a chromatographic run time of 4 min and a linear calibration curve ranging from 0.05 to 10 ng/mL (r2 > 0.99). The limit of quantification was 0.05 ng/mL. This HPLC/MS/MS procedure was used to assess the bioequivalence of cyproheptadine in two cyproheptadine + cobamamide (4 mg + 1 mg) tablet formulations (Cobactin® [cyproheptadine + cobamamide] test formulation supplied from Zambon Laboratórios Farmacêuticos Ltda. and Cobavital® from Solvay Farma (standard reference formulation)). A single 4 mg + 1 mg [cyproheptadine + cobamamide] dose of each formulation was administered to healthy volunteers. The study was conducted using an open, randomized, two-period crossover design with a 1-week washout interval. Since the 90% CI for Cmax and AUCs ratios were all within the 80-125% bioequivalence limit proposed by the US Food and Drug Administration, it was concluded that the cyproheptadine test formulation (Cobactin®) is bioequivalent to the Cobavital® formulation for both the rate and the extent of absorption of cyproheptadine. Copyright © 2011 John Wiley & Sons, Ltd.

  20. Bioequivalence of 2 Formulations of Sildenafil Oral Soluble Film 100 mg and Sildenafil Citrate (Viagra) 100 mg Oral Tablets in Healthy Male Volunteers.

    Science.gov (United States)

    Dadey, Eric

    Sildenafil citrate tablets (VIAGRA; Pfizer Inc) have been used since 1998 as an oral therapy for the treatment of erectile dysfunction. However, in some cases, patients may have difficulty in swallowing tablets, and the need to use water to aid in the oral administration of the tablets has the potential to interrupt the sexual encounter, reduce spontaneity, and therefore decrease the quality of the experience. Two oral soluble film (OSF) formulations of sildenafil were developed using MonoSol Rx's proprietary PharmFilm technology. Both films were formulated to dissolve rapidly on the tongue, thereby releasing the drug into the oral cavity, whereupon it is swallowed without the use of water. From a patient perspective, it is anticipated that the film formulations of sildenafil citrate will provide a more compliant and discreet dosage form. The purpose of this clinical study was to compare the bioequivalence of the 2 sildenafil OSF 100 mg formulations (MonoSol Rx, LLC) with the sildenafil citrate 100 mg tablets. The design was a single-dose, randomized, open-label, 3-period, 6-sequence, 3-treatment, single-center, crossover study conducted in 18 healthy, nonsmoking male volunteers under fasting conditions, with each treatment period separated by a 7-day washout period. Plasma sildenafil concentrations were measured predose and then periodically to 24 hours after dosing. The 90% confidence intervals for plasma sildenafil AUC0-t, AUC0-∞, and Cmax for both sildenafil OSF formulations as compared with sildenafil citrate tablets were all within the 80%-125% range, indicating bioequivalence of both film formulations to sildenafil citrate tablets. Overall, the demonstrated bioequivalence coupled with the performance advantages of an OSF dosage form (ie, rapid dissolution in the mouth, can be taken without water, and can be dosed discreetly) suggest that the sildenafil OSF may provide an attractive alternative to sildenafil citrate oral tablets.

  1. 76 FR 80878 - Solicitation of Veterinary Shortage Situation Nominations for the Veterinary Medicine Loan...

    Science.gov (United States)

    2011-12-27

    ... the American Veterinary Medical Association (JAVMA), and sponsored by the Food Supply Veterinary... by the American Veterinary Medical Association (AVMA) in the spring of 2009, the average educational... grateful to the Association of American Veterinary Medical Colleges (AAVMC), the American Veterinary...

  2. 76 FR 5131 - Solicitation of Nomination of Veterinary Shortage Situations for the Veterinary Medicine Loan...

    Science.gov (United States)

    2011-01-28

    ... the American Veterinary Medical Association (JAVMA), and sponsored by the Food Supply Veterinary... by the American Veterinary Medical Association (AVMA) in the spring of 2009, the average educational... grateful to the Association of American Veterinary Medical Colleges (AAVMC), the American Veterinary...

  3. Challenges and opportunities in polymer technology applied to veterinary medicine.

    Science.gov (United States)

    Bermudez, J M; Cid, A G; Ramírez-Rigo, M V; Quinteros, D; Simonazzi, A; Sánchez Bruni, S; Palma, S

    2014-04-01

    An important frontier in the administration of therapeutic drugs to veterinary species is the use of different polymers as drug delivery platforms. The usefulness of polymers as platforms for the administration of pharmaceutical and agricultural agents has been clearly recognized in the recent decades. The chemical versatility of polymers and the wide range of developed controlled-release strategies enhance the possibilities for the formulation of active molecules. In particular, the veterinary area offers opportunities for the development of novel controlled-release drug delivery technologies adapted to livestock or companion animal health needs. In some cases, it also allows to improve profitability in meat production or to meet the safety criteria related to drug residues. A number of factors affect the selection of polymers and subsequent properties of the controlled-release drug delivery system. However, their selection also dictates the release kinetics of the drug from the delivery system. Such choices are therefore crucial as they affect the success and potential of the delivery system for achieving the therapeutic goals of the veterinarian. It is the intention of this review to give an overview of the most relevant polymers, which are used or have been tested as drug delivery release rate modifiers in the veterinary field. The article highlights some recent developments focusing on their advantages and applications and analyzes the future direction of the scientific and technological advancements in this area. © 2013 John Wiley & Sons Ltd.

  4. Center for Veterinary Medicine (CVM)

    Data.gov (United States)

    Federal Laboratory Consortium — As seen on the center's logo, the mission statement for FDA's Center for Veterinary Medicine (CVM) reads: "Protecting Human and Animal Health." To achieve this broad...

  5. Workforce needs in veterinary medicine

    National Research Council Canada - National Science Library

    Board on Agriculture and Natural Resources; Board on Higher Education and Workforce; Division on Earth and Life Studies; Policy and Global Affairs; National Research Council

    2013-01-01

    In a study of the issues related to the veterinary medical workforce, including demographics, workforce supply, trends affecting job availability, and capacity of the educational system to fill future...

  6. Towards a humane veterinary education.

    Science.gov (United States)

    Martinsen, Siri; Jukes, Nick

    2005-01-01

    There is a vast array of learning tools and approaches to veterinary education, many tried and true, many innovative and with potential. Such new methods have come about partly from an increasing demand from both students and teachers to avoid methods of teaching and training that harm animals. The aim is to create the best quality education, ideally supported by validation of the efficacy of particular educational tools and approaches, while ensuring that animals are not used harmfully and that respect for animal life is engendered within the student. In this paper, we review tools and approaches that can be used in the teaching of veterinary students, tools and approaches that ensure the dignity and humane treatment of animals that all teachers and students must observe as the very ethos of the veterinary profession that they serve. Veterinary education has not always met, and still often does not meet, this essential criterion.

  7. Stem cells in veterinary medicine

    OpenAIRE

    Fortier, Lisa A; Travis, Alexander J

    2011-01-01

    The stem cell field in veterinary medicine continues to evolve rapidly both experimentally and clinically. Stem cells are most commonly used in clinical veterinary medicine in therapeutic applications for the treatment of musculoskeletal injuries in horses and dogs. New technologies of assisted reproduction are being developed to apply the properties of spermatogonial stem cells to preserve endangered animal species. The same methods can be used to generate transgenic animals for production o...

  8. Welcome to Veterinary Medicine: Research and Reports

    OpenAIRE

    Musser JMB

    2011-01-01

    Musser Jeffrey MBDepartment of Veterinary Pathobiology, College of Veterinary Medicine, Texas A&M University, TX, USAThis year marks the 250th anniversary of the Royal Veterinary School in Lyon, France, the world's first veterinary college. Since its inception, many changes have occurred in veterinary medicine such as views on education and didactic learning, demographics of our profession, and standards of practice in animal husbandry, medicine, surgery, anesthesia, and vacci...

  9. Clinical Bioequivalence of OT329 SOLIS and ADVAIR DISKUS in Adults with Asthma.

    Science.gov (United States)

    Longphre, Malinda V; Getz, Elise Burmeister; Fuller, Rick

    2017-02-01

    OT329 SOLIS is a generic candidate for the branded asthma treatment, ADVAIR DISKUS (fluticasone propionate/salmeterol xinafoate), and, as such, the manufacturer is required to provide evidence of clinical "bioequivalence" as a condition for regulatory approval. The objective of the current study was to determine if SOLIS and DISKUS provided bioequivalent improvements in lung function at two time points: Day 1 and Week 4. This study was a randomized, multiple-dose, placebo-controlled, parallel-group design conducted in the United States (NCT02260492) with a 2-week run-in followed by a 4-week treatment period. Consenting patients were randomized to treatment with OT329 SOLIS 100/50, ADVAIR DISKUS 100/50, or placebo. Lung function was measured predose and 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours after the first dose to test equivalence of the β-agonist salmeterol component based on FEV1 area under the curve (0-12 h). After 4 weeks of twice-daily dosing, trough (predose) FEV1 was measured to evaluate equivalence of the fluticasone propionate corticosteroid component. Bioequivalence was concluded if the 90% confidence interval (CI) for the ratio of the products fell within 80-125%. Of the 1,524 screened, 879 patients with asthma were randomized to treatment (n = 418 SOLIS, 419 DISKUS, 42 placebo). OT329 SOLIS and ADVAIR DISKUS were bioequivalent at Day 1, with an FEV1 area under the curve (0-12 h) test/reference ratio of 108% (90% CI = 94-122%). Likewise, the products were bioequivalent at Week 4 with a trough FEV1 test/reference ratio of 105% (90% CI = 90-119). Both active treatments were superior to placebo (P bioequivalence of OT329 SOLIS to ADVAIR DISKUS. Clinical trial registered with www.clinicaltrials.gov (NCT02260492).

  10. One world of veterinary medicine.

    Science.gov (United States)

    King, L J

    2009-08-01

    The veterinary profession finds itself in the midst of a new world order. Today veterinarians are part of a world that is exquisitely interconnected culturally, economically, socially, and professionally. As a consequence, societal needs and expectations of the profession are more demanding, critical and far-reaching. Veterinarians must play important roles in five intersecting domains of work: public health, bio-medical research, global food safety and security, ecosystem health and the more traditional role of caring for animals. To be successful in this broad and complex range of services and activities, veterinarians must possess an expanded knowledge base, acquire new skills, and develop a new mindset that will ensure their success and excellence in all these domains. The veterinary profession is becoming more fragmented and specialised, and it needs to be brought back together by a single sphere of knowledge or discipline that can serve as an intellectual foundation. The concept of One World of Veterinary Medicine can do just that. With this mindset veterinarians will become better connected to the world around and gain new public recognition and esteem. To achieve this, a special commitment by academic veterinary medicine is, of course, essential. Veterinary schools must lead an educational transformation that reaffirms the social contract of veterinarians and works to align diverse sectors, build a global community, find a common purpose and expand the 21st Century veterinary portfolio of services, activities, and new possibilities.

  11. Governance, veterinary legislation and quality.

    Science.gov (United States)

    Petitclerc, M

    2012-08-01

    This review of governance distinguishes between ends and means and, by highlighting the complexity and differing definitions of the concept, defines its scope and focuses discussion on its characteristics in order to establish an interrelationship between veterinary legislation and governance. Good governance must be backed by legislation, and good legislation must incorporate the principles and instruments of good governance. This article lists some of the main characteristics of governance and then reviews them in parallel with the methodology used to draft veterinary legislation, emphasising the importance of goal-setting and stakeholder participation. This article describes the criteria developed by the Veterinary Legislation Support Programme (VLSP) of the World Organisation for Animal Health (OIE) for assessing the quality of veterinary legislation. It then makes a comparison between the quality assurance process and the good governance process in order to demonstrate that the introduction and proper use of the tools for developing veterinary legislation offered by the OIE VLSP leads to a virtuous circle linking legislation with good governance. Ultimately, the most important point remains the implementation of legislation. Consequently, the author points out that satisfactory implementation relies not only on legislation that is technically and legally appropriate, acceptable, applicable, sustainable, correctly drafted, well thought through and designed for the long term, but also on the physical and legal capacity of official Veterinary Services to perform their administrative and enforcement duties, and on there being the means available for all those involved to discharge their responsibilities.

  12. Relative bioavailability and bioequivalence of a newly developed fixed combination sachet of acetylsalicylic acid and pseudoephedrine compared with a preliminary combination.

    Science.gov (United States)

    Lücker, P W; Birkel, M; Hey, B; Loose, I; Schaefer, A

    2003-10-01

    Acetylsalicylic acid (ASA) and pseudoephedrine (PSE) are often administered together for the treatment of symptoms of the common cold, i.e., nasal congestion, runny nose, sore throat and headache. Based on this fact we developed a fixed combination of 500 mg ASA and 30 mg PSE, the recommended doses for both drugs for treating symptoms of the common cold, as granulate to be dissolved in water for administration. The purpose of this open, randomized, three-factorial (three-treatment, three-period, six-sequence) Latin Square clinical study was to investigate the relative bioavailability of ASA and PSE as well as the establishment of bioequivalence after single administration of the fixed combination (final formulation for approval) of 500 mg ASA/30 mg PSE*HCl and the preliminary formulation of this combination. Pharmacokinetic characteristics AUC(norm) and C(max,norm) of ASA, its metabolite SA, and PSE, were determined as measure of rate and extent of absorption of the two formulations. The treatment ratios final/preliminary formulation and their corresponding 90% confidence intervals were calculated to establish bioequivalence. Additionally, descriptive statistics were calculated for the parameters t(max), t((1/2)), and mean residence time (MRT). In total, data from 18 healthy male volunteers were included in the pharmacokinetic evaluation. The primary target parameters were analyzed using an analysis of variance (ANOVA) after logarithmic transformation of the data. Confidence intervals of 90% were calculated for the geometric means of ratios using the mean square error term of the ANOVA. Bioequivalence criteria were fulfilled for AUC(norm) and C(max,norm). Geometric means of individual ratios of AUC(norm) and of C(max,norm) showed equal bioavailability of the new formulation compared with the preliminary. Furthermore, a relative bioavailability of approximately 100% of the preliminary formulation was shown for the newly developed formulation for all parameters. The

  13. Bioavailability and bioequivalence of two oral formulations of alendronate sodium 70 mg: an open-label, randomized, two-period crossover comparison in healthy Korean adult male volunteers.

    Science.gov (United States)

    Rhim, Si-Youn; Park, Jin-Hee; Park, Yoo-Sin; Lee, Min-Ho; Kim, Dong-Sun; Shaw, Leslie M; Yang, Seok-Chul; Kang, Ju-Seop

    2009-05-01

    Alendronate sodium is a Bisphosphonate drug used to treat and prevent osteoporosis and several other bone diseases. A new formulation has been developed and is currently awaiting regulatory approval, pending findings on bioequivalence. The aims of the present study were to compare the bioavailability and pharmacokinetic (PK) properties, and to determine the bioequivalence, of a test and reference formulation of alendronate sodium 70 mg in a healthy Korean adult male population. This open-label, randomized, 2-sequence, 2-period crossover study was carried out at Hanyang University Medical Center (Seoul, Republic of Korea). Healthy Korean adult male volunteers were randomly assigned to receive a single 70-mg dose of the test or reference formulation of alendronate sodium, administered with 240 mL of water, followed by a 7-day washout period and administration of the alternate formulation. The study drugs were administered after a 12-hour overnight fast. Serial blood samples were collected and adverse events were monitored by a clinical investigator via observation, personal interview, and vital signs (blood pressure, heart rate, and body temperature) over a 7-hour period (at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, and 7 hours) after drug administration. Plasma alendronate sodium concentrations were determined using a validated high-performance liquid chromatographic-postcolumn fluorescence derivatization method, with visible detection in the range of 2 to 100 ng/mL and lower limit of quantification set at 2 ng/mL. PK properties, including AUC(0-t), AUC(0-infinity), C(max), T(max), t(1/2), and the elimination constant (k(e)), were determined using non-compartmental analysis. The formulations were considered bioequivalent if the 90% CI ratios for C(max) and AUC were within the predetermined interval of 80% to 125%, the regulatory definition set by the US Food and Drug Administration (FDA). Twenty-three healthy male volunteers (mean [SD] age, 23.5 [2.0] years [range, 19

  14. Pharmacokinetic properties and bioequivalence of 2 formulations of valsartan 160-mg tablets: A randomized, single-dose, 2-period crossover study in healthy Korean male volunteers.

    Science.gov (United States)

    Kim, Ji-Eon; Ki, Min-Hyo; Yoon, In-Soo; Cho, Hyun-Jong; Kim, Ree-Sun; Tae Kim, Geun; Kim, Dae-Duk

    2014-02-01

    The solubility of valsartan is dependent on pH and thus may cause patient variability in drug absorption and failure in bioequivalence studies; thus, increasing the solubility and release of valsartan at low pH has been suggested for a more favorable pharmacokinetic profile. However, due to this pH dependence, the change in the formulation process could alter the disintegration and/or dissolution profile of the drug, possibly making the results of bioequivalence studies misleading. The aim of this study was to assess the bioavailability and tolerability of a newly developed oral formulation of valsartan 160 mg (wet-granulation tablet) in healthy Korean male volunteers. This study was performed with the subjects under fasted conditions, using a randomized, single-dose, 2-period crossover design. Subjects were assigned to receive, in randomized order, a single dose of the test formulation and a reference formulation (valsartan 160-mg dry-granulation tablet), with a washout period of 7 days between the administrations. Blood samples were collected up to 24 hours after dosing, and pharmacokinetic parameters were determined after the plasma valsartan concentration was analyzed using UPLC-MS/MS. The dissolution studies of both formulations were conducted using USP apparatus 2 at 50 rpm with 1000 mL of phosphate buffer solution (pH, 6.8) at 37°C ± 0.5°C. Bioequivalence was defined per Korean Food and Drug Administration's regulatory criteria as 90% CIs of the geometric mean test/reference ratios of AUC0-t and Cmax within the range of 0.8 to 1.25. Tolerability was assessed using physical examination and subject interviews. Sixty subjects were enrolled (mean [SD] age [range], 23.6 [2.4] years [21-31]; height, 173.7 [6.6] cm [161-190]; and weight, 68.0 [8.7] kg [54-85]). The mean AUC0-∞ values with the test and reference tablets were 31,784 (13,844) and 32,714 (14,512) ng · h/mL, respectively; Cmax, 5094 (2061) and 5064 (1864) ng/mL; Tmax, 2.92 (1.04) and 3.08 (1

  15. The history of veterinary cardiology.

    Science.gov (United States)

    Buchanan, James W

    2013-03-01

    Throughout civilization, animals have played a pivotal role in the advancement of science and medicine. From as early as 400 BC when Hippocrates recognized that diseases had natural causes, the steadfast advances made by biologists, scientists, physicians and scholars were fueled by timely and important facts and information- much of it gained through animal observations that contributed importantly to understanding anatomy, physiology, and pathology. There have been many breakthroughs and historic developments. For example, William Harvey in the 16th and 17th centuries clarified the importance of the circulatory system, aided by observations in dogs and pigs, which helped to clarify and confirm his concepts. The nineteenth century witnessed advances in physical examination techniques including auscultation and percussion. These helped create the basis for enhanced proficiency in clinical cardiology. An explosion of technologic advances that followed in the 20th century have made possible sophisticated, accurate, and non-invasive diagnostics. This permitted rapid patient assessment, effective monitoring, the development of new cardiotonic drugs, clinical trials to assess efficacy, and multi-therapy strategies. The latter 20th century has marshaled a dizzying array of advances in medical genetics and molecular science, expanding the frontiers of etiologies and disease mechanisms in man, with important implications for animal health. Veterinary medicine has evolved during the last half century, from a trade designed to serve agrarian cultures, to a diverse profession supporting an array of career opportunities ranging from private, specialty practice, to highly organized, specialized medicine and subspecialty academic training programs in cardiology and allied disciplines. Copyright © 2013 Elsevier B.V. All rights reserved.

  16. Pharmacokinetics and bioequivalence of a liquid formulation of hydroxyurea in children with sickle cell anemia.

    Science.gov (United States)

    Estepp, Jeremie H; Melloni, Chiara; Thornburg, Courtney D; Wiczling, Paweł; Rogers, Zora; Rothman, Jennifer A; Green, Nancy S; Liem, Robert; Brandow, Amanda M; Crary, Shelley E; Howard, Thomas H; Morris, Maurine H; Lewandowski, Andrew; Garg, Uttam; Jusko, William J; Neville, Kathleen A

    2016-03-01

    Hydroxyurea (HU) is a crucial therapy for children with sickle cell anemia, but its off-label use is a barrier to widespread acceptance. We found HU exposure is not significantly altered by liquid vs capsule formulation, and weight-based dosing schemes provide consistent exposure. HU is recommended for all children starting as young as 9 months of age with sickle cell anemia (SCA; HbSS and HbSβspan(0) thalassemia); however; a paucity of pediatric data exists regarding the pharmacokinetics (PK) or the exposure-response relationship of HU. This trial aimed to characterize the PK of HU in children and to evaluate and compare the bioavailability of a liquid vs capsule formulation. This multicenter; prospective; open-label trial enrolled 39 children with SCA who provided 682 plasma samples for PK analysis following administration of HU. Noncompartmental and population PK models are described. We report that liquid and capsule formulations of HU are bioequivalent; weight-based dosing schemes provide consistent drug exposure; and age-based dosing schemes are unnecessary. These data support the use of liquid HU in children unable to swallow capsules and in those whose weight precludes the use of fixed capsule formulations. Taken with existing safety and efficacy literature; these findings should encourage the use of HU across the spectrum of age and weight in children with SCA; and they should facilitate the expanded use of HU as recommended in the National Heart; Lung; and Blood Institute guidelines for individuals with SCA. © 2015, The American College of Clinical Pharmacology.

  17. Comparative in vitro dissolution and in vivo bioequivalence of two diclofenac enteric coated formulations.

    Science.gov (United States)

    Basmenji, Saeed; Valizadeh, Hadi; Zakeri-Milani, Parvin

    2011-01-01

    The aim of this study was the comparison of in vitro dissolution and in vivo bioavailability of two different brands of diclofenac sodium (CAS 15307-86-5) enteric coated tablets in healthy male Iranian volunteers in a single-dose, randomized, open-label, single blind study, which was conducted according to a crossover design in healthy volunteers. A washout interval of two weeks was selected between administrations to each subject in this study. Serial venous blood samples over 10 h after each administration to measure diclofenac sodium concentration in serum were obtained, and placed into tubes containing sodium heparin. Then the plasma was separated and kept frozen at -20 degrees C for subsequent analysis with a modified HPLC method with UV detection. In addition, the in vitro dissolution study was performed on the brands. For the test and reference formulation, mean Cmax values were 2257.3 (ng/ml) and 2156 (ng/ml), respectively. The mean AUC(0)tau and AUC(0)infinity were 5726.1 (ng x h/ml) and 5917.8 (ng x h/ml) for the test and 5689.9 (ng x h/ml) and 5967.4 (ng x h/ml) for the reference formulation, respectively. Results show that the 90% confidence intervals for the ratio of test and reference products in Cmax (101.4-114.9%), AUC(0)tau (96.3-109.1%) and AUC(0)infinity (94.7-107.3%) were all within the 80-125% interval proposed by the FDA and EMA. Both formulations released > 80% of drug within 30 min in buffer pH = 6.8 medium. Therefore the diclofenac sodium enteric coated tablets of the test and reference formulations are bioequivalent in terms of rate and extent of absorption.

  18. A comparison of antimicrobial usage in human and veterinary medicine in France from 1999 to 2005.

    Science.gov (United States)

    Moulin, Gérard; Cavalié, Philippe; Pellanne, Isabelle; Chevance, Anne; Laval, Arlette; Millemann, Yves; Colin, Pierre; Chauvin, Claire

    2008-09-01

    The antimicrobials allowed and amounts sold in veterinary and human medicine in France were compared to see if the same antimicrobial drugs are used in veterinary and human medicine, and to the same extent. Registers of all approved antimicrobial commercial products, kept by the French Agency for Veterinary Medicinal Products (AFSSA ANMV) for animals and the French Health Products Safety Agency (AFSSAPS) for humans, were compared to determine whether the same antimicrobials were approved in 2007 for use in both human and animal populations. Sales data were collected from pharmaceutical companies between 1999 and 2005 by the AFSSA ANMV and AFSSAPS. Usage of the different antimicrobial anatomical therapeutic chemical (ATC) classes in human and veterinary medicines was recorded. Data were expressed in tonnes of active ingredients and were then related to the animal and human biomasses to compare usages expressed in mg/kg. All antimicrobial ATC classes were used in both human and veterinary medicine. Tetracyclines accounted for the most sales in veterinary medicine. beta-Lactams predominated in human medicine. A decrease in the amounts consumed by both human and animal populations was observed during the study. In 2005, 760 tonnes were used in human medicine and 1320 tonnes in veterinary medicine, corresponding to 199 and 84 mg/kg of live weight in human and animal populations, respectively. The same antimicrobial drugs were used in human and veterinary medicines but the quantitative patterns of use were different. Expression of antimicrobial usage is a key point to address when comparing usage trends.

  19. 75 FR 48352 - Determination That MOTRIN (Ibuprofen) Tablets and Four Other Drug Products Were Not Withdrawn...

    Science.gov (United States)

    2010-08-10

    ... of duplicate versions of drug products approved under an ANDA procedure. ANDA applicants must, with... was previously approved. ANDA applicants do not have to repeat the extensive clinical testing... ANDA are data to show that the drug that is the subject of the ANDA is bioequivalent to the listed drug...

  20. Human health hazards of veterinary medications: information for emergency departments.

    Science.gov (United States)

    Lust, Elaine Blythe; Barthold, Claudia; Malesker, Mark A; Wichman, Tammy O

    2011-02-01

    There are over 5000 approved prescription and over-the-counter medications, as well as vaccines, with labeled indications for veterinary patients. Of these, there are several products that have significant human health hazards upon accidental or intentional exposure or ingestion in humans: carfentanil, clenbuterol (Ventipulmin), ketamine, tilmicosin (Micotil), testosterone/estradiol (Component E-H and Synovex H), dinoprost (Lutalyse/Prostamate), and cloprostenol (Estromate/EstroPlan). The hazards range from mild to life-threatening in terms of severity, and include bronchospasm, central nervous system stimulation, induction of miscarriage, and sudden death. To report medication descriptions, human toxicity information, and medical management for the emergent care of patients who may have had exposure to veterinary medications when they present to an emergency department (ED). The intended use of this article is to inform and support ED personnel, drug information centers, and poison control centers on veterinary medication hazards. There is a need for increased awareness of the potential hazards of veterinary medications within human medicine circles. Timely reporting of veterinary medication hazards and their medical management may help to prepare the human medical community to deal with such exposures or abuses when time is of the essence. Copyright © 2011 Elsevier Inc. All rights reserved.

  1. Review of hazards to female reproductive health in veterinary practice.

    Science.gov (United States)

    Scheftel, Joni M; Elchos, Brigid L; Rubin, Carol S; Decker, John A

    2017-04-15

    OBJECTIVE To review publications that address female reproductive health hazards in veterinary practice, summarize best practices to mitigate reproductive risks, and identify current knowledge gaps. DESIGN Systematized review. SAMPLE English-language articles describing chemical, biological, and physical hazards present in the veterinary workplace and associations with adverse reproductive outcomes or recommendations for minimizing risks to female reproductive health. PROCEDURES Searches of the CAB abstracts database were performed in July 2012 and in May 2015 with the following search terms: veterinarians AND occupational hazards and vets.id AND occupational hazards.sh. Searches of the PubMed database were conducted in November 2012 and in May 2015 with the following medical subject heading terms: occupational exposure AND veterinarians; anesthetics, inhalation/adverse effects AND veterinarians; risk factors AND pregnancy AND veterinarians; pregnancy outcome AND veterinarians; and animal technicians AND occupational exposure. Two additional PubMed searches were completed in January 2016 with the terms disinfectants/toxicity AND female AND fertility/drug effects and veterinarians/psychology AND stress, psychological. No date limits were applied to searches. RESULTS 4 sources supporting demographic trends in veterinary medicine and 118 resources reporting potential hazards to female reproductive health were identified. Reported hazards included exposure to anesthetic gases, radiation, antineoplastic drugs, and reproductive hormones; physically demanding work; prolonged standing; and zoonoses. CONCLUSIONS AND CLINICAL RELEVANCE Demographic information suggested that an increasing number of women of reproductive age will be exposed to chemical, biological, and physical hazards in veterinary practice. Information on reproductive health hazards and minimizing risk, with emphasis on developing a safety-focused work culture for all personnel, should be discussed starting

  2. Veterinary education as leader: which alternatives?

    Science.gov (United States)

    Waldau, Paul

    2007-01-01

    This article suggests that veterinary medicine has a leadership role to play in our society on ethical matters involving non-human animals. The article contrasts two trends within veterinary medicine; the first trend is a continuation of the avowedly utilitarian attitude toward non-humans that has its roots in Western veterinary medicine's eighteenth-century origins, and the second is the implicit view in veterinary practice that animals matter in and of themselves. Using the idea of alternatives in research and teaching, the article suggests that, in the years to come, veterinary medicine's answers to the relationships of these two trends will shape not only the soul of veterinary medicine, veterinary education, and the veterinary profession but, just as importantly, the larger society and culture themselves. This text is based on the keynote address delivered at the AAVMC Education Symposium in Washington, DC, on March 9, 2006, under the title "Ethical Issues Impacting Animal Use in Veterinary Medical Teaching."

  3. Bioequivalence study of two formulations of flupirtine maleate capsules in healthy male Chinese volunteers under fasting and fed conditions

    Directory of Open Access Journals (Sweden)

    Liu YF

    2017-12-01

    Full Text Available Yanfang Liu, Hua Huo, Zhibo Zhao, Wenli Hu, Yujia Sun, Yunbiao Tang Technical Center for Clinical Pharmacy, Department of Drug Clinical Trail Management Agency, General Hospital of Shenyang Military Area Command, Shenyang, China Aim: This study developed a high-performance liquid chromatography–tandem mass spectrometry method to simultaneously determine the concentrations of flupirtine and its major active metabolite D-13223 in human plasma in order to assess the bioequivalence (BE of two flupirtine maleate capsules among healthy male Chinese volunteers under fasting and fed conditions. Materials and methods: There were two single-center, randomized, single-dose, open-label, laboratory-blinded, two-period, cross-over studies which included 24 healthy male Chinese volunteers under fasting and fed conditions, respectively. Plasma samples were collected prior to and up to 48 h after dosing. The concentrations of flupirtine and its major active metabolite D-13223 in plasma samples were determined by a validated method, that is, high-performance liquid chromatography coupled with a tandem mass spectrometry detector. Pharmacokinetic metrics of area from time zero to the last measurable concentration (AUC0-t, area under the plasma concentration–time curve from administration to infinite time (AUC0-∞, and Cmax were used for BE assessment. Results: Forty-eight healthy volunteers who met the criteria were enrolled and completed the study. According to the observation of vital signs and laboratory measurement, no volunteers had any adverse reactions. Under fasting condition, the geometric mean ratios (90% CI of the test/reference drug for flupirtine were 103.0% (98.1%–108.2% for AUC0-t, 102.9% (98.2%–107.9% for AUC0-∞, and 97.0% (85.9%–109.5% for Cmax. Under fed condition, the geometric mean ratios (90% CI of the test/reference drug for flupirtine were 101.7% (98.4%–105.1% for AUC0-t, 101.6% (98.5%–104.8% for AUC0-∞, and 103.5% (94.7%

  4. Investigation of the bioequivalence of montelukast chewable tablets after a single oral administration using a validated LC-MS/MS method

    Directory of Open Access Journals (Sweden)

    Zaid AN

    2015-09-01

    Full Text Available Abdel Naser Zaid,1 Murad N Abualhasan,1 David G Watson,2 Ayman Mousa,3 Nadia Ghazal,4 Rana Bustami5 1Department of Pharmacy, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, Palestine; 2Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK; 3R&D Department, Avalon Pharma (Middle East Pharmaceutical Industries Co. Ltd., Riyadh, Kingdom of Saudi Arabia; 4Naratech Pharmaceutical Consultancy, 5Pharmaceutical Research Unit, Amman, Jordan Background: Montelukast (MT is a leukotriene D4 antagonist. It is an effective and safe medicine for the prophylaxis and treatment of chronic asthma. It is also used to prevent acute exercise-induced bronchoconstriction and as a symptomatic relief of seasonal allergic rhinitis and perennial allergic rhinitis.Objective: The aim of this study was to evaluate the bioequivalence (BE of two drug products: generic MT 5 mg chewable tablets versus the branded drug Singulair® pediatric 5 mg chewable tablets among Mediterranean volunteers.Methods: An open-label, randomized two-period crossover BE design was conducted in 32 healthy male volunteers with a 9-day washout period between doses and under fasting conditions. The drug concentrations in plasma were quantified by using a newly developed and fully validated liquid chromatography tandem mass spectrometry method, and the pharmacokinetic parameters were calculated using a non-compartmental model. The ratio for generic/branded tablets using geometric least squares means was calculated for both the MT products.Results: The relationship between concentration and peak area ratio was found to be linear within the range 6.098–365.855 ng/mL. The correlation coefficient (R2 was always greater than 0.99 during the course of the validation. Statistical comparison of the main pharmacokinetic parameters showed no significant difference between the generic and branded products. The point estimates (ratios of

  5. Average bioequivalence of two oral formulations of fluconazole in healthy subjects after multiple dosing.

    Science.gov (United States)

    Atanasova, I; Bozhinova, K; Terziivanov, D

    1999-06-01

    To assess the average bioequivalence of two oral dosage forms of fluconazole--test (Fungolon, Antibiotic Co.) and reference (Diflucan, Pfizer)--in 18 healthy volunteers in a multiple dose-balanced, two-period, crossover study design. The dosage regimen consisted of seven days treatment (first day 100 mg and 50 mg thereafter for six days given orally) and a washout period of two weeks between different treatments. Plasma samples were taken at regular time intervals according to the study protocol for measuring of plasma fluconazole concentrations. The primary and secondary parameters AUC(168-192), Cav, %PTF, Cmax, %Swing, %AUCF, 100 Cmax/AUC, T above Cav, and Tmax were estimated. The point estimates--geometric means of the ratios test (T)/reference (R) and the 90% confidence intervals (CI) for the ratios of expected medians (T)/(R), assuming a multiplicative model, estimated by parametric and nonparametric analysis--were in the defined ranges for accepting of bioequivalence for two of the primary metrics. The point estimates and the 90% CIs after parametric analysis of AUC(168-192) were 1.00 (0.98-1.02) and for the metric %PTF exceeded the accepted range for bioequivalence after parametric analysis the point estimate and 90% CI were 0.93 and (0.799-1.08). The two preparations were considered to be bioequivalent in the rate and extent of absorption with significant variability across subjects.

  6. Application of dermal microdialysis for the evaluation of bioequivalence of a ketoprofen topical gel

    DEFF Research Database (Denmark)

    Tettey-Amlalo, Ralph Nii Okai; Kanfer, Isadore; Skinner, Michael F

    2008-01-01

    The purpose was to investigate dermal microdialysis (DMD) for the assessment of the bioavailability of a ketoprofen topical gel formulation and to evaluate this technique as a tool for the determination of bioequivalence. Four microdialysis probes were inserted into the dermis on the volar aspect...

  7. Pilot and Repeat Trials as Development Tools Associated with Demonstration of Bioequivalence.

    Science.gov (United States)

    Fuglsang, Anders

    2015-05-01

    The purpose of this work is to use simulated trials to study how pilot trials can be implemented in relation to bioequivalence testing, and how the use of the information obtained at the pilot stage can influence the overall chance of showing bioequivalence (power) or the chance of approving a truly bioinequivalent product (type I error). The work also covers the use of repeat pivotal trials since the difference between a pilot trial followed by a pivotal trial and a pivotal trial followed by a repeat trial is mainly a question of whether a conclusion of bioequivalence can be allowed after the first trial. Repeating a pivotal trial after a failed trial involves dual or serial testing of the bioequivalence null hypothesis, and the paper illustrates how this may inflate the type I error up to almost 10%. Hence, it is questioned if such practice is in the interest of patients. Tables for power, type I error, and sample sizes are provided for a total of six different decision trees which allow the developer to use either the observed geometric mean ratio (GMR) from the first or trial or to assume that the GMR is 0.95. In cases when the true GMR can be controlled so as not to deviate more from unity than 0.95, sequential design methods ad modum Potvin may be superior to pilot trials. The tables provide a quantitative basis for choosing between sequential designs and pivotal trials preceded by pilot trials.

  8. 77 FR 10535 - Final Guidances for Industry Describing Product-Specific Bioequivalence Recommendations...

    Science.gov (United States)

    2012-02-22

    ... guidances represent the Agency's current thinking on product-specific design of BE studies to support ANDAs... bioequivalence (BE) recommendations. The recommendations provide product-specific guidance on the design of BE... Recommendations for Specific Products,'' which explained the process that would be used to make product-specific...

  9. 78 FR 19271 - Draft Guidance for Industry on Bioequivalence Recommendations for Metronidazole Vaginal Gel...

    Science.gov (United States)

    2013-03-29

    ... finalized, will represent the Agency's current thinking on the design of BE studies to support ANDAs for... guidance provides specific recommendations on the design of bioequivalence (BE) studies to support... for Specific Products,'' which explained the process that would be used to make product-specific...

  10. NIGERIAN VETERINARY JOURNAL

    African Journals Online (AJOL)

    ADEYEYE

    practice in Nigeria. The objective of this study was to evaluate the pattern of drugs prescription in dogs diagnosed with CPE in some small animal clinics in Nigeria. MATERIALS AND METHODS ... presumptive and/or laboratory diagnoses. Data obtained from individual .... be appropriate and prudent. There is currently no ...

  11. Comparative bioequivalence studies of tramadol hydrochloride sustained-release 200 mg tablets

    Directory of Open Access Journals (Sweden)

    Suhas S Khandave

    2010-11-01

    Full Text Available Suhas S Khandave1, Satish V Sawant1, Santosh S Joshi1, Yatish K Bansal2, Sonal S Kadam21Accutest Research Laboratories (I Private Limited, Koparkhirne, Navi Mumbai, Maharashtra, India; 2Ipca Laboratories Limited, Kandivli Mumbai, Maharashtra, IndiaBackground: Tramadol hydrochloride is available as 50 mg immediate-release (IR and 100 mg, 200 mg, and 300 mg sustained-release (SR tablets. The recommended dose of tramadol is 50–100 mg IR tablets every 4–6 hours. The tramadol SR 200 mg tablet is a better therapeutic option, with a reduced frequency of dosing, and improved patient compliance and quality of life. The present study evaluated the bioequivalence of a generic tramadol SR 200 mg tablet.Methods: A comparative in vitro dissolution study was performed on the test and reference products, followed by two separate single-dose bioequivalence studies under fasting and fed conditions and one multiple-dose bioequivalence study under fasting conditions. These bioequivalence studies were conducted in healthy human subjects using an open-label, randomized, two-treatment, two-period, two-sequence, crossover design. The oral administration of the test and reference products was done on day 1 for both the single-dose studies and on days 1–5 for the multiple-dose study in each study period as per the randomization code. Serial blood samples were collected at predefined time points in all the studies. Analysis of plasma concentrations of tramadol and O-desmethyltramadol (the M1 metabolite was done by a validated liquid chromatography-mass spectrometry analytical method. The standard acceptance criterion of bioequivalence was applied on log-transformed pharmacokinetic parameters for tramadol and its M1 metabolite.Results: The ratios for geometric least-square means and 90% confidence intervals were within the acceptance range of 80%–125% for log-transformed primary pharmacokinetic parameters for tramadol and its M1 metabolite in all the three studies

  12. Physical ergonomics in veterinary dentistry.

    Science.gov (United States)

    DeForge, Donald H

    2002-12-01

    Ergonomics is the application of a body of knowledge addressing the interactions between man and the total working environment, such as atmosphere, heat, light and sound, as well as all tools and equipment of the workplace. Work related musculoskeletal injuries, caused by poor posture, have been discussed in human dentistry for several years. Veterinary dentistry, as a relatively new specialty within veterinary medicine, should address the ergonomics of poor posture without further delay to prevent work-related injuries. The generalist, as well as the specialist and their technicians, are subject to various neck and back disorders if proper ergonomic recommendations are not followed. This review article highlights basic ergonomic design principles for illumination and posture in veterinary dentistry.

  13. A Sensitive Liquid Chromatographic Method for the Analysis of Clarithromycin with Pre-Column Derivatization: Application to a Bioequivalence Study

    Directory of Open Access Journals (Sweden)

    Amir Farshchi

    2009-03-01

    Full Text Available Objective(sA sensitive liquid chromatographic method for the analysis of clarithromycin- a macrolide antibiotic- in human serum, using pre-column derivatization with 9-fluorenylmethyl chloroformate (FMOC-Cl is described. Materials and MethodsThe method involved liquid–liquid extraction of the drug and an internal standard (amantadine followed by pre-column derivatization of the analytes with FMOC-Cl. A mixture of 0.05 M phosphate buffer containing triethylamine (2 ml/l; pH 3.8 and methanol (17:83, v/v was used as mobile phase and chromatographic separation was achieved on a Shimpack CLC-ODS column. The eluate was monitored by a fluorescence detector with respective excitation and emission wavelengths of 265 and 315 nm. ResultsThe analytical method was linear over the concentration range of 0.025-10 μg/ml of clarithromycin in human serum with a limit of quantification of 0.025 μg/ml. The assay is sensitive enough to measure drug levels obtained in human single dose studies.ConclusionIn the present method, sensitivity and the running time of analysis have been improved and successfully applied in a bioequivalence study of three different clarithromycin preparations in 12 healthy volunteers.

  14. Integrative veterinary medical education and consensus guidelines for an integrative veterinary medicine curriculum within veterinary colleges.

    Science.gov (United States)

    Memon, M A; Shmalberg, J; Adair, H S; Allweiler, S; Bryan, J N; Cantwell, S; Carr, E; Chrisman, C; Egger, C M; Greene, S; Haussler, K K; Hershey, B; Holyoak, G R; Johnson, M; Jeune, S Le; Looney, A; McConnico, R S; Medina, C; Morton, A J; Munsterman, A; Nie, G J; Park, N; Parsons-Doherty, M; Perdrizet, J A; Peyton, J L; Raditic, D; Ramirez, H P; Saik, J; Robertson, S; Sleeper, M; Dyke, J Van; Wakshlag, J

    2016-01-01

    Integrative veterinary medicine (IVM) describes the combination of complementary and alternative therapies with conventional care and is guided by the best available evidence. Veterinarians frequently encounter questions about complementary and alternative veterinary medicine (CAVM) in practice, and the general public has demonstrated increased interest in these areas for both human and animal health. Consequently, veterinary students should receive adequate exposure to the principles, theories, and current knowledge supporting or refuting such techniques. A proposed curriculum guideline would broadly introduce students to the objective evaluation of new veterinary treatments while increasing their preparation for responding to questions about IVM in clinical practice. Such a course should be evidence-based, unbiased, and unaffiliated with any particular CAVM advocacy or training group. All IVM courses require routine updating as new information becomes available. Controversies regarding IVM and CAVM must be addressed within the course and throughout the entire curriculum. Instructional honesty regarding the uncertainties in this emerging field is critical. Increased training of future veterinary professionals in IVM may produce an openness to new ideas that characterizes the scientific method and a willingness to pursue and incorporate evidence-based medicine in clinical practice with all therapies, including those presently regarded as integrative, complementary, or alternative.

  15. Integrative veterinary medical education and consensus guidelines for an integrative veterinary medicine curriculum within veterinary colleges

    Science.gov (United States)

    Memon, M.A.; Shmalberg, J.; Adair, H.S.; Allweiler, S.; Bryan, J.N.; Cantwell, S.; Carr, E.; Chrisman, C.; Egger, C.M.; Greene, S.; Haussler, K.K.; Hershey, B.; Holyoak, G.R.; Johnson, M.; Jeune, S. Le; Looney, A.; McConnico, R.S.; Medina, C.; Morton, A.J.; Munsterman, A.; Nie, G.J.; Park, N.; Parsons-Doherty, M.; Perdrizet, J.A.; Peyton, J.L.; Raditic, D.; Ramirez, H.P.; Saik, J.; Robertson, S.; Sleeper, M.; Dyke, J. Van; Wakshlag, J.

    2016-01-01

    Integrative veterinary medicine (IVM) describes the combination of complementary and alternative therapies with conventional care and is guided by the best available evidence. Veterinarians frequently encounter questions about complementary and alternative veterinary medicine (CAVM) in practice, and the general public has demonstrated increased interest in these areas for both human and animal health. Consequently, veterinary students should receive adequate exposure to the principles, theories, and current knowledge supporting or refuting such techniques. A proposed curriculum guideline would broadly introduce students to the objective evaluation of new veterinary treatments while increasing their preparation for responding to questions about IVM in clinical practice. Such a course should be evidence-based, unbiased, and unaffiliated with any particular CAVM advocacy or training group. All IVM courses require routine updating as new information becomes available. Controversies regarding IVM and CAVM must be addressed within the course and throughout the entire curriculum. Instructional honesty regarding the uncertainties in this emerging field is critical. Increased training of future veterinary professionals in IVM may produce an openness to new ideas that characterizes the scientific method and a willingness to pursue and incorporate evidence-based medicine in clinical practice with all therapies, including those presently regarded as integrative, complementary, or alternative. PMID:27200270

  16. Renal scintigraphy in veterinary medicine.

    Science.gov (United States)

    Tyson, Reid; Daniel, Gregory B

    2014-01-01

    Renal scintigraphy is performed commonly in dogs and cats and has been used in a variety of other species. In a 2012 survey of the members of the Society of Veterinary Nuclear Medicine, 95% of the respondents indicated they perform renal scintigraphy in their practice. Renal scintigraphy is primarily used to assess renal function and to evaluate postrenal obstruction. This article reviews how renal scintigraphy is used in veterinary medicine and describes the methods of analysis. Species variation is also discussed. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Laser use in veterinary dentistry.

    Science.gov (United States)

    Bellows, Jan

    2002-05-01

    Lasers have been used in human dentistry since the 1960's. Lasers can provide a veterinary dentist access to difficult to reach areas with a relatively bloodless surgical field. Due to vaporization of nerve endings, human patients undergoing laser dental treatment reveal less pain compared to scalpel driven procedures. Dental applications for the commonly used lasers are discussed, as are special safety precautions. Many dental procedures enhanced by a carbon dioxide laser are covered. Future applications for the laser in veterinary dentistry are also discussed.

  18. Veterinary applications of infrared thermography.

    Science.gov (United States)

    Rekant, Steven I; Lyons, Mark A; Pacheco, Juan M; Arzt, Jonathan; Rodriguez, Luis L

    2016-01-01

    Abnormal body temperature is a major indicator of disease; infrared thermography (IRT) can assess changes in body surface temperature quickly and remotely. This technology can be applied to a myriad of diseases of various etiologies across a wide range of host species in veterinary medicine. It is used to monitor the physiologic status of individual animals, such as measuring feed efficiency or diagnosing pregnancy. Infrared thermography has applications in the assessment of animal welfare, and has been used to detect soring in horses and monitor stress responses. This review addresses the variety of uses for IRT in veterinary medicine, including disease detection, physiologic monitoring, welfare assessment, and potential future applications.

  19. Health risk from veterinary antimicrobial use in China's food animal production and its reduction.

    Science.gov (United States)

    Hu, Yuanan; Cheng, Hefa

    2016-12-01

    The overuse and misuse of veterinary drugs, particularly antimicrobials, in food animal production in China cause environmental pollution and wide food safety concerns, and pose public health risk with the selection of antimicrobial resistance (AMR) that can spread from animal populations to humans. Elevated abundance and diversity of antimicrobial resistance genes (ARGs) and resistant bacteria (including multi-drug resistant strains) in food-producing animals, food products of animal origin, microbiota of human gut, and environmental media impacted by intensive animal farming have been reported. To rein in drug use in food animal production and protect public health, the government made a total of 227 veterinary drugs, including 150 antimicrobial products, available only by prescription from licensed veterinarians for curing, controlling, and preventing animal diseases in March 2014. So far the regulatory ban on non-therapeutic use has failed to bring major changes to the long-standing practice of drug overuse and misuse in animal husbandry and aquaculture, and significant improvement in its implementation and enforcement is necessary. A range of measures, including improving access to veterinary services, strengthening supervision on veterinary drug production and distribution, increasing research and development efforts, and enhancing animal health management, are recommended to facilitate transition toward rational use of veterinary drugs, particularly antimicrobials, and to reduce the public health risk arising from AMR development in animal agriculture. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Determination of platinum surface contamination in veterinary and human oncology centres using inductively coupled plasma mass spectrometry

    NARCIS (Netherlands)

    Janssens, T.; Brouwers, E. E M; de Vos, J. P.; de Vries, N.; Schellens, J. H M; Beijnen, J. H.

    2015-01-01

    The objective of this study was to determine the surface contamination with platinum-containing antineoplastic drugs in veterinary and human oncology centres. Inductively coupled plasma mass spectrometry was used to measure platinum levels in surface samples. In veterinary and human oncology

  1. Bioequivalence Study of a New Fixed-dose Combination Tablet Containing S-Amlodipine Nicotinate and Olmesartan Medoxomil in Healthy Korean Male Subjects.

    Science.gov (United States)

    Oh, Mi Jin; Hwang, Hyun Hwan; Kim, Hyun Gyu; Lee, Geun Hyeog; Cho, Yun-Seok; Lee, Sun Young; Kang, Soo Yeon; Cho, Kyung Hee; Lee, Yun Young; Lee, Yun Jeong; Jang, Choon-Gon; Lee, Seok-Yong

    2017-07-01

    A fixed-dose combination (FDC) pill of amlodipine (relatively old calcium channel blocker as dihydropyridine) and olmesartan (relatively new angiotensin II receptor blocker) is used for hypertension that is not adequately controlled with a single-formulation drug. Because the FDC is a one-pill formulation, and amlodipine and olmesartan have different mechanisms of action, it is expected to improve patients' medication compliance and have an increased blood pressure-lowering efficacy. The purpose of this study was to assess the safety profile and the bioequivalence of two different FDC formulations [amlodipine besylate/olmesartan medoxomil 10/40 mg (reference product) and S-amlodipine nicotinate/olmesartan medoxomil 5/40 mg (test product)]. A randomized, open-label, single-dose, 2-treatment, 2-way, and 2-period crossover study, including a 3-week washout period, was performed in 32 healthy Korean male volunteers. To analyze the concentration of S-amlodipine or olmesartan, plasma samples were collected up to 144 hours after the dose for S-amlodipine and 48 hours after the dose for olmesartan. Pharmacokinetic parameters, including the Cmax and the area under the curve from time 0 to the last measurable concentration (AUC0-last) for the time versus concentration plot, were calculated. Analysis of variance for bioequivalence was conducted using Cmax and AUC0-last converted to log scale, and the mean ratios and 90% CIs were determined. Safety data included analysis of adverse events (AEs), vital signs, physical examinations, clinical laboratory test, and 12-lead ECGs. Of the 32 enrolled participants, 29 healthy volunteers completed the study. For both S-amlodipine and olmesartan, the main pharmacokinetic parameters were all within the acceptable range for regulatory bioequivalence. The 90% CIs for the geometric mean ratios of Cmax and AUC0-last were 0.8766 to 0.9760 and 0.8288 to 0.9224, respectively, for S-amlodipine and 0.9097 to 1.1229 and 0.8904 to 1

  2. Bioequivalence of vildagliptin/metformin fixed-dose combination tablets and a free combination of vildagliptin and metformin in healthy subjects.

    Science.gov (United States)

    He, Y-L; Paladini, S; Sabia, H; Campestrini, J; Zhang, Y; Leon, S; Ligueros-Saylan, M; Jarugula, V

    2008-05-01

    To assess the bioequivalence of vildagliptin/metformin fixed-dose combination tablets (at doses of 50/500, 50/850 and 50/1,000 mg) with free combination of the individual drugs in healthy subjects. The pharmacokinetics of vildagliptin and metformin following administration of a fixed-dose combination tablet of vildagliptin/metformin at doses of 50/500 mg (Study I), 50/850 mg (Study II) and 50/1,000 mg (Study III) compared with administration of the individual drugs as free combinations were investigated. All three studies were open-label, single-center, randomized, two-period, two-treatment crossover studies in healthy subjects. Pharmacokinetic parameters (AUC(0-infinity), C(max), t(max), t(1/2) and CL/F) for vildagliptin and metformin across the three studies were similar whether vildagliptin and metformin were administered as a single fixed-dose combination tablet (vildagliptin/metformin 50/500, 50/850 or 50/1,000 mg) or as the respective individual tablets. The point estimates and 90% CI of the geometric mean ratios for vildagliptin and metformin C(max), AUC(0-t), and AUC(0-infinity) were all within the predefined bioequivalence range of 0.80 - 1.25. Administration of the vildagliptin/metformin combination tablets was well tolerated; the incidence of adverse events was similar to that observed with the respective free combinations of vildagliptin and metformin, and the most common individual adverse events were mild gastrointestinal events, which are commonly observed with metformin treatment. The fixed-dose combination tablet of vildagliptin/metformin is bioequivalent to administration of the individual drugs as a free combination at dose levels of 50/500, 50/850 and 50/1,000 mg and is well tolerated. Consequently, the fixed-dose combination tablets are considered therapeutically equivalent and exchangeable to the free combination in clinical practice. Furthermore, the fixed-dose combination tablets are expected to enhance convenience and thereby improve

  3. Evaluation of the Most Frequently Prescribed Extemporaneously Compounded Veterinary Medications at a Large Independent Community Pharmacy.

    Science.gov (United States)

    Karara, Adel H; Hines, Ryan; Demir, Zehra; Nnorom, Bethran; Horsey, Robert; Twigg, Geoffrey

    2016-01-01

    Extemporaneous drug formulation is essential to provide optimal pharmaceutical care to veterinary patients. The need for this is exacerbated by the fact that commercially produced veterinary-specific products, without a human indication, require specialty veterinary manufacturing facilities and a new animal drug application process to gain marketing approval. This study examined the prescription patterns of extemporaneously compounded veterinary preparations in the compounding department at a large independent community pharmacy. Data was obtained from a total of 1348 prescriptions requiring extemporaneous compounding over the course of a two-year period (2014-2015). A database was constructed and each compounded prescription was allocated to a therapeutic category based on the American Hospital Formulary Service Drug Information. Data analysis showed that the most commonly prescribed preparations belonged to the central nervous system (39%), anti-infective agents (21%), and hormones (12%) therapeutic categories. Overall, suspensions were the most dispensed (47%), extemporaneously compounded dosage forms followed by solutions (28%), and capsules (10%). The majority (88%) of compounded preparations were administered by the oral route. The top three drugs that are compounded for veterinary medicine were (1) potassium bromide oral solution for canine epilepsy, (2) methimazole solution used to treat hyperthyroidism in cats, and (3) metronidazole suspension, an antibiotic for the treatment of diarrhea and other infections in dogs and cats. Remarkably, our findings are in good agreement with previously published survey data on the top drugs that are compounded for veterinary medicine. In the era of personalized medicine, veterinary extemporaneous compounding for specialized needs will continue to play an important role providing optimum therapy for veterinary patients. Copyright© by International Journal of Pharmaceutical Compounding, Inc.

  4. Pharmacovigilance in veterinary medicine in Chile: a pilot study.

    Science.gov (United States)

    Iragüen, D; Urcelay, S; San Martín, B

    2011-04-01

    Iragüen, D., Urcelay, S., San Martín, B. Pharmacovigilance in veterinary medicine in Chile: a pilot study. J. vet. Pharmacol. Therap.34, 108-115. In Chile, there is no present government policy to survey and analyse adverse drug reactions (ADRs) in the field of veterinary medicine. The intent of this study is to assess, for the first time, ADR frequency in treated animals. To this purpose, a 6-month period pilot study based on WHO recommendations was conducted to monitor ADRs in cats and dogs for frequently used drugs and common labelled signs. Of a total of 149 detected ADRs, 29 (6 in cats and 23 in dogs) were notified by means of ADR report forms, while the rest was identified after reviewing patient clinical records, thus evidencing strong under-reporting problems. More than 70% of ADRs were related to antimicrobials, vaccines and tranquilizers. In dogs, there was a significant effect on ADRs' presentation when acepromazine, amoxicillin, carprofen, ivermectin, sextuple vaccine (polyvalent vaccine that confers immunity against canine distemper virus, canine parvovirus, Leptospira canicola, L. icterohemmoragiae, canine adenovirus type 2 and canine parainfluenza virus) and phytomenadione (subcutaneous injection) were administered. In the case of cats, a significant influence on ADRs was detected when acepromazine, amoxicillin or vitamin K was administered. Present results suggest the need for a pharmacovigilance programme in veterinary medicine for timely ADR-presenting drug detection and drug safety improvement. © 2010 Blackwell Publishing Ltd.

  5. Fosfomycin: Uses and potentialities in veterinary medicine

    Directory of Open Access Journals (Sweden)

    D.S. Pérez

    2014-03-01

    Full Text Available Fosfomycin (FOS is a natural bactericidal broad-spectrum antibiotic which acts on proliferating bacteria by inhibiting cell wall and early murein/peptidoglycan synthesis. Bactericidal activity is evident against Gram positive and Gram negative bacteria and can also act synergistically with other antibiotics. Bacterial resistance to FOS may be natural or acquired. Other properties of this drug include inhibition of bacterial adhesion to epithelial cells, exopolysaccharide biofilm penetration, immunomodulatory effect, phagocytosis promotion and protection against the nephrotoxicity caused by other drugs. FOS has chemical characteristics not typically observed in organic phosphoric compounds and its molecular weight is almost the lowest of all the antimicrobials. It tends to form salts easily due to its acidic nature (disodium salt, for intravenous (IV, intramuscular (IM and subcutaneous (SC administration; calcium and trometamol salt: for oral (PO administration. FOS has a very low protein binding (<0.5% which, along with its low molecular weight and water solubility, contributes to its good diffusion into fluids (cerebrospinal fluid, aqueous and vitreous humor, interstitial fluid and tissues (placenta, bone, muscle, liver, kidney and skin/fat. In all species, important differences in the bioavailability have been found after administration in relation to the various derivatives of FOS salts. Pharmacokinetic profiles have been described in humans, chickens, rabbits, cows, dogs, horses and weaning piglets. The low toxicity and potential efficacy of FOS are the main factors that contribute to its use in humans and animals. Thus, it has been used to treat a broad variety of bacterial infections in humans, such as localized peritonitis, brain abscesses, severe soft tissue infections, cystitis and other conditions. In veterinary medicine, FOS is used to treat infectious diseases of broiler chickens and pigs. In broilers, it is administered for the

  6. The Literature of Veterinary Medicine. CE 60.

    Science.gov (United States)

    Kerker, Ann E.; Malamud, Judie

    This course guide outlines the objectives and content for a professional continuing education course on the literature of veterinary medicine. Topics covered include: (1) an introduction to veterinary medicine as a discipline, including comparison with other medical sciences, veterinary medicine education, licensure, animal models, veterinary…

  7. Sokoto Journal of Veterinary Sciences: Editorial Policies

    African Journals Online (AJOL)

    Focus and Scope. The Sokoto Journal of Veterinary Sciences publishes original research articles related to veterinary sciences, including livestock health and production, diseases of wild life and fish, preventive veterinary medicine and zoonoses among others. Case reports, review articles and editorials are also accepted.

  8. Establishing veterinary education in North America.

    Science.gov (United States)

    Jones, Bruce Vivash

    2013-01-12

    The American Veterinary Medical Association is marking its 150th anniversary in 2013, celebrating '150 years of education, science and service'. As Bruce Vivash Jones explains, veterinary surgeons from the UK played a key role in establishing a system of veterinary education in North America.

  9. Sokoto Journal of Veterinary Sciences

    African Journals Online (AJOL)

    um chafe

    2. 1Faculty of Veterinary Medicine, Ahmadu Bello Unviersity, Zaria, Nigeria. 2College of Agriculture and Animal Science, Ahmadu Bello University, Mando, Kaduna, Nigeria. Correspondence Author: Abstract. Village chickens in Kaduna State, Nigeria were vaccinated once with a Malaysian heat-resistant Newcastle disease ...

  10. Veterinary Microbiology, 3rd Edition

    Science.gov (United States)

    Veterinary Microbiology, Third Edition is organized into four sections and begins with an updated and expanded introductory section on infectious disease pathogenesis, diagnosis and clinical management. The second section covers bacterial and fungal pathogens, and the third section describes viral d...

  11. Veterinary clinical nutrition: success stories: an overview.

    Science.gov (United States)

    Davies, Mike

    2016-08-01

    In this overview of success stories in veterinary clinical nutrition topics in cats and dogs reviewed include the dietary management of chronic kidney disease, dissolution of urinary tract uroliths by dietary modification, the recognition that taurine and L-carnitine deficiencies can cause dilated cardiomyopathy; that clinical signs associated with feline hyperthyroidism (caused by a benign adenoma) can be controlled by a low-iodine diet alone; that dietary management of canine osteoarthritis can also reduce non-steroidal anti-inflammatory drug doses; and that disease-free intervals and survival times can be statistically longer in dogs with Stage III lymphoma managed with diet. As we discover more about nutrigenetics and nutrigenomics, and as we expand our basic understanding of idiopathic diseases we are bound to identify more nutritionally related causes, and be able to develop novel dietary strategies to manage disease processes, including the formulation of diets designed to alter gene expression to obtain beneficial clinical outcomes.

  12. Bioequivalence of two formulations of pregabalin 150-mg capsules under fasting conditions in healthy male subjects
.

    Science.gov (United States)

    Lee, Hyun A; Lee, SeungHwan; Yim, Sung-Vin; Kim, Bo-Hyung

    2017-02-01

    Pregabalin binds to the α2δ auxiliary subunit of voltage-gated calcium channels, which are widely distributed throughout the central and peripheral nervous systems and modulate calcium-dependent neurotransmitter release. Pregabalin is indicated for the treatment of peripheral and central neuropathic pain, partial seizures with or without secondary generalization, and treatment of generalized anxiety disorder (GAD). The purpose of this study was to assess the bioequivalence of two different formulations of pregabalin 150-mg capsules in healthy Korean male subjects under fasting conditions. This bioequivalence study was based on an open-label, single-dose, randomized, 2-period, 2-sequence crossover design with a washout period of 7 days. Blood samples for pharmacokinetic (PK) evaluation were collected up to 24 hours postdose. Plasma concentrations of pregabalin were determined using a validated LC-MS/MS method. PK parameters were determined using noncompartmental analysis. Bioequivalence was assumed if the 90% confidence intervals (CIs) for the test/reference ratios of log-transformed Cmax and AUClast values met the bioequivalence criteria specified by Korean regulatory guidelines (90% CI 0.8 - 1.25). The extent of exposure in terms of AUClast amounted to 26,018.3 - 3,580.8 µg×h/L for the test formulation and 25,680.2 ± 3,083.6 µg×h/L for the reference formulation. Cmax reached values of 4,782.7 ± 1,124.2 µg/L and 4,654.0 ± 911.4 µg/L for the test product and reference product, respectively. The geometric mean ratio and 90% CIs of the test product to the reference product were 1.0132 (0.9862 - 1.0351) for AUClast and 1.0153 (0.9351 - 1.1044) for Cmax, which were well within the range necessary to establish bioequivalence (90% CI 0.8 - 1.25). The bioequivalence between test and reference formulations under fasting conditions was confirmed both in terms of the rate and extent of absorption.
.

  13. TSH-Based Protocol, Tablet Instability, and Absorption Effects on L-T4 Bioequivalence

    Science.gov (United States)

    DiStefano, Joseph J.

    2009-01-01

    Background FDA Guidance for pharmacokinetic (PK) testing of levothyroxine (L-T4) for interbrand bioequivalence has evolved recently. Concerns remain about efficacy and safety of the current protocol, based on PK analysis following supraphysiological L-T4 dosing in euthyroid volunteers, and recent recalls due to intrabrand manufacturing problems also suggest need for further refinement. We examine these interrelated issues quantitatively, using simulated what-if scenarios testing efficacy of a TSH-based protocol and tablet stability and absorption, to enhance precision of L-T4 bioequivalence methods. Methods We use an updated simulation model of human thyroid hormone regulation quantified and validated from data that span a wide range of normal and abnormal thyroid system function. Bioequivalence: We explored a TSH-based protocol, using normal replacement dosing in simulated thyroidectomized patients, switching brands after 8 weeks of full replacement dosing. We simulated effects of tablet potency differences and intestinal absorption differences on predicted plasma TSH, T4, and triiodothyronine (T3) dynamics. Stability: We simulated effects of potency decay and lot-by-lot differences in realistic scenarios, using actual tablet potency data spanning 2 years, comparing the recently reduced 95–105% FDA-approved potency range with the original 90–110% range. Results A simulated decrease as small as 10–15% in L-T4 or its absorption generated TSH concentrations outside the bioequivalence target range (0.5–2.5 mU/L TSH), whereas T3 and T4 plasma levels were maintained normal. For a 25% reduction, steady-state TSH changed 300% (from 1.5 to 6 mU/L) compared with bioequivalent between lots and between fresh and near-expired tablets. Conclusions A pharmacodynamic TSH-measurement bioequivalence protocol, using normal L-T4 replacement dosing in athyreotic volunteers, is likely to be more sensitive and safer than current FDA Guidance based on T4 PK. The tightened 95

  14. WHAT IS THERAPEUTIC EQUIVALENCE OF GENERIC DRUG AND HOW TO PROVE IT

    Directory of Open Access Journals (Sweden)

    N. P. Kutishenko

    2011-01-01

    Full Text Available The problem of generic drugs use in clinical practice and confirmation of their therapeutic equivalence is discussed. The significance of studies on generic drugs bioequivalence, as well as details of international practice and regulations in this area is explained.

  15. Bioequivalence evaluation of two capsule formulations of amoxicillin in healthy adult male bangladeshi volunteers: A single-dose, randomized, open-label, two-period crossover study.

    Science.gov (United States)

    Ullah, Ashik; Azad, Mohammad Abul Kalam; Sultana, Rebeka; Akbor, Maruf Mohammad; Hasan, Ahasanul; Latif, Mahbub; Hasnat, Abul

    2008-12-01

    Amoxicillin, a semisynthetic penicillin antibiotic, is widely prescribed in Bangladesh due to its extended spectrum and its rapid and extensive oral absorption with good tolerability. Although a number of generic oral formulations of amoxicillin are available in Bangladesh, a study of the bioequivalence and pharmacokinetic properties of these formulations has not yet been conducted in a Bangladeshi population. The aim of this study was to assess the pharmacokinetic properties and bioequivalence of 2 formulations of amoxicillin 500-mg capsules (test, SK-mox(®); reference, Amoxil-Bencard(®)) using serum data. This single-dose, randomized, open-label, 2-period crossover study was conducted in healthy male subjects in compliance with the Declaration of Helsinki and International Conference on Harmonisation guidelines. Subjects were assigned to receive the test or the reference drug as a single-dose, 500-mg capsule under fasting conditions after a 1-week washout period. After oral administration, blood samples were collected and analyzed for amoxicillin concentration using a validated high-performance liquid chromatography method. The pharmacokinetic parameters were determined using a noncompartmental method. The formulations were considered bioequivalent if the natural log-transformed ratios of pharmacokinetic parameters were within the predetermined equivalence range of 80% to 125%, according to the US Food and Drug Administration (FDA) requirement. Twenty-four healthy adult male Bangladeshi volunteers (mean [SD] age, 26.92 [3.37] years; age range, 23-34 years; mean [SD] body mass index, 23.O9 [1.58] kg/m(2)) participated in the study. Using serum data, the values obtained for the test and reference formulations, respectively, were as follows: Cmax, 9.85 (2.73) and 10.63 (2.12) μg/mL; Tmax, 1.29 (0.58) and 1.33 (0.49) hours; and AUC0-12, 27.09 (7.62) and 28.56 (6.30) μg/mL · h(-1). No period, sequence, or formulation effects were observed; however, significant

  16. The history of veterinary medicine in Namibia

    Directory of Open Access Journals (Sweden)

    Herbert P. Schneider

    2012-04-01

    Full Text Available Until the middle of the 19th century, very few references exist regarding the occurrence of animal diseases in Namibia. With the introduction of contagious bovine pleuropneumonia (CBPP in 1859, this picture changed completely and livestock owners implemented various forms of disease control in an effort to contain the spread of this disease and minimise its devastating effects. After the establishment of the colonial administration in 1884, the first animal disease legislation was introduced in 1887 and the first veterinarian, Dr Wilhelm Rickmann, arrived in 1894. CBPP and the outbreak of rinderpest in 1897 necessitated a greatly expanded veterinary infrastructure and the first veterinary laboratory was erected at Gammams near Windhoek in 1897. To prevent the spread of rinderpest, a veterinary cordon line was established, which was the very beginning of the Veterinary Cordon Fence as it is known today. After the First World War, a small but dedicated corps of veterinarians again built up an efficient animal health service in the following decades, with veterinary private practice developing from the mid–1950s. The veterinary profession organised itself in 1947 in the form of a veterinary association and, in 1984, legislation was passed to regulate the veterinary profession by the establishment of the Veterinary Council of Namibia. The outbreak of foot and mouth disease in 1961 was instrumental in the creation of an effective veterinary service, meeting international veterinary standards of quality and performance which are still maintained today.

  17. The history of veterinary medicine in Namibia.

    Science.gov (United States)

    Schneider, Herbert P

    2012-05-16

    Until the middle of the 19th century, very few references exist regarding the occurrence of animal diseases in Namibia. With the introduction of contagious bovine pleuropneumonia (CBPP) in 1859, this picture changed completely and livestock owners implemented various forms of disease control in an effort to contain the spread of this disease and minimise its devastating effects. After the establishment of the colonial administration in 1884, the first animal disease legislation was introduced in 1887 and the first veterinarian, Dr Wilhelm Rickmann, arrived in 1894. CBPP and the outbreak of rinderpest in 1897 necessitated a greatly expanded veterinary infrastructure and the first veterinary laboratory was erected at Gammams near Windhoek in 1897. To prevent the spread of rinderpest, a veterinary cordon line was established, which was the very beginning of the Veterinary Cordon Fence as it is known today. After the First World War, a small but dedicated corps of veterinarians again built up an efficient animal health service in the following decades, with veterinary private practice developing from the mid-1950s. The veterinary profession organised itself in 1947 in the form of a veterinary association and, in 1984, legislation was passed to regulate the veterinary profession by the establishment of the Veterinary Council of Namibia. The outbreak of foot and mouth disease in 1961 was instrumental in the creation of an effective veterinary service, meeting international veterinary standards of quality and performance which are still maintained today.

  18. Determination of itopride hydrochloride in human plasma by RP-HPLC with fluorescence detection and its use in bioequivalence study.

    Science.gov (United States)

    Ma, Jing; Yuan, Li-Hua; Ding, Mei-Juan; Zhang, Jun; Zhang, Qing; Xu, Qun-Wei; Zhou, Xue-Min

    2009-03-01

    A sensitive, selective and simple method using a precipitation of protein with 10% perchloric acid, followed by high-performance liquid chromatography (HPLC) with fluorescence detection was developed for the determination of itopride hydrochloride in human plasma, using levofloxacin as the internal standard (IS). Chromatographic separation was obtained within 7.0 min using a reverse phase Hypersil BDS C(18) (250 mm x 4.6 mm, 5 microm) column and an isocratic mobile phase, constituting of a mixture of 0.1 mol/l ammonium acetate-methanol (30:70, v/v) flowing at 1.1 ml/min. The excitation and emission wavelengths were set at 304 and 344 nm, respectively. The method was validated over the concentration range of 5 ng/ml to 1000.0 ng/ml. The lower limit of quantitation (LLOQ) was 5 ng/ml. The extractive recovery of itopride hydrochloride from the biological matrix was more than 80.77%. The intra-day accuracy of the drug containing serum samples was more than 82.94% with a precision of 2.81-4.37%. The inter-day accuracy was 82.91% or more, with a precision of 6.89-9.54%. The limit we have used (70-143%) is based on the local regulatory authority (SFDA). The developed method was validated and successfully applied to bioequivalence studies of itopride hydrochloride in healthy male volunteers.

  19. Assessing the bioequivalence of biosimilars: The Retacrit case

    NARCIS (Netherlands)

    Schellekens, H.|info:eu-repo/dai/nl/068406762

    2009-01-01

    This first phase of the first generation of modern biotechnology-derived protein drugs is now coming to an end with the expiration of their patents and consequently the possibility of the marketing of copies. The generic paradigm used for classical drugs cannot, however, be applied to therapeutic

  20. Veterinary vaccines against Toxoplasma gondii.

    Science.gov (United States)

    Innes, Elisabeth A; Bartley, Paul M; Maley, Stephen; Katzer, Frank; Buxton, David

    2009-03-01

    Toxoplasma gondii has a very wide intermediate host range and is thought to be able to infect all warm blooded animals. The parasite causes a spectrum of different diseases and clinical symptoms within the intermediate hosts and following infection most animals develop adaptive humoral and cell-mediated immune responses. The development of protective immunity to T. gondii following natural infection in many host species has led researchers to look at vaccination as a strategy to control disease, parasite multiplication and establishment in animal hosts. A range of different veterinary vaccines are required to help control T. gondii infection which include vaccines to prevent congenital toxoplasmosis, reduce or eliminate tissue cysts in meat producing animals and to prevent oocyst shedding in cats. In this paper we will discuss some of the history, challenges and progress in the development of veterinary vaccines against T. gondii.

  1. Anxiety in veterinary surgical students

    DEFF Research Database (Denmark)

    Langebæk, Rikke; Eika, Berit; Jensen, Asger Lundorff

    2012-01-01

    in a Surgical Skills Lab (SSL) has an anxiety reducing effect. Investigations were carried out as a comparative study and a parallel group study. Potential participants were fourth-year veterinary students who attended a surgical course (Basic Surgical Skills) and a non-surgical course (Clinical Examination......The surgical educational environment is potentially stressful and this can negatively affect students' learning. The aim of this study was to investigate whether veterinary students' level of anxiety is higher in a surgical course than in a non-surgical course and if pre-surgical training...... anxiety questionnaires (Spielberger's state-trait anxiety inventory and Cox and Kenardy's performance anxiety questionnaire) were used. Anxiety levels were measured before the non-surgical course (111 students from 2009) and before live-animal surgery during the surgical course (153 students from 2009...

  2. Veterinary vaccines against Toxoplasma gondii

    Directory of Open Access Journals (Sweden)

    Elisabeth A Innes

    2009-03-01

    Full Text Available Toxoplasma gondii has a very wide intermediate host range and is thought to be able to infect all warm blooded animals. The parasite causes a spectrum of different diseases and clinical symptoms within the intermediate hosts and following infection most animals develop adaptive humoral and cell-mediated immune responses. The development of protective immunity to T. gondii following natural infection in many host species has led researchers to look at vaccination as a strategy to control disease, parasite multiplication and establishment in animal hosts. A range of different veterinary vaccines are required to help control T. gondii infection which include vaccines to prevent congenital toxoplasmosis, reduce or eliminate tissue cysts in meat producing animals and to prevent oocyst shedding in cats. In this paper we will discuss some of the history, challenges and progress in the development of veterinary vaccines against T. gondii.

  3. Emotions in veterinary surgical students

    DEFF Research Database (Denmark)

    Langebæk, Rikke; Eika, Berit; Pedersen, Lene Tanggaard

    2012-01-01

    A surgical educational environment is potentially stressful and can negatively affect students' learning. The aim of the present study was to investigate the emotions experienced by veterinary students in relation to their first encounter with live-animal surgery and to identify possible sources...... of positive and negative emotions, respectively. During a Basic Surgical Skills course, 155 veterinary fourth-year students completed a survey. Of these, 26 students additionally participated in individual semi-structured interviews. The results of the study show that students often experienced a combination...... of emotions; 63% of students experienced negative emotions, while 58% experienced positive ones. In addition, 61% of students reported feeling excited or tense. Students' statements reveal that anxiety is perceived as counterproductive to learning, while excitement seems to enhance students' focus...

  4. Pain management in veterinary patients

    Directory of Open Access Journals (Sweden)

    H. S. Vedpathak

    Full Text Available The veterinary practitioner has an ethical obligation to help alleviate animal pain. Although most veterinarians accept the fact that animals feel pain, still, postoperative pain relief is not a routine practice in all veterinary hospitals and clinics today. Nociception is a physiological process which involves transduction, transmission, modulation and perception of the noxious stimuli. Chemical mediators are important components of the nociceptive reflex and offer a target of pharmacologic modulation. Assessment of pain in animals is the most important step in the successful management of pain. Choosing appropriate method of pain control would depend upon the type of procedure followed, severity of pain and economic considerations for each individual circumstance. Our understanding of the pain in its manifestation, mechanisms, assessment and alleviation in animals is still although improving, limited. [Vet World 2009; 2(9.000: 360-363

  5. Dental Education in Veterinary Medicine

    OpenAIRE

    Diana L. Eubanks

    2011-01-01

    Periodontal disease is among the most prevalent canine dis-eases affecting over 75% of dogs. Strengthening of the human-animal bond and the increasing education of the aver-age pet owner, have fostered a heightened awareness of periodontal care in dogs and cats. Industry support has further assisted the small animal veterinarian in providing quality dental treatments and prevention. As recently as the 1990’s, veterinary curriculums contained little or no dental training. That trend is changin...

  6. Bioequivalence of eslicarbazepine acetate from two different sources of its active product ingredient in healthy subjects.

    Science.gov (United States)

    Falcão, Amílcar; Lima, Ricardo; Sousa, Rui; Nunes, Teresa; Soares-da-Silva, Patrício

    2013-06-01

    To compare the bioavailability (BA) and pharmacokinetic (PK) properties and to demonstrate the bioequivalence (BE) between two active product ingredient (API) sources of eslicarbazepine acetate (ESL) in healthy volunteers. Forty healthy male and female subjects aged 18-40 years were randomized to treatment with 400 or 800 mg ESL marketed (MF) formulation [current active pharmaceutical ingredient (API) source] and 400 or 800 mg ESL to-be-marketed (TBM) formulation (new API source) under a gender-balanced, two-period, two-sequence crossover open-label study design. Subjects were assigned to receive either 400 or 800 mg ESL dose strengths, and each was randomly administered on two occasions--either a single oral tablet of MF or a single oral tablet of TBM--separated by a washout period of at least 7 days. Formulations were to be considered bioequivalent if, for both 400 or 800 mg ESL dosage strengths, the test (TBM)/reference (MF) geometric mean ratios (GMR) and 90% confidence intervals (90% CI) of the area under the plasma concentration-time curve (AUC) and peak plasma concentration (Cmax) were within the predetermined range of 80-125%. Test/reference GMR (90% CI) for the Cmax and AUC was respectively 100% (94-109%) and 96% (94-98%) following 400 mg ESL and 100% (95-105%) and 100% (97-103%) following 800 mg ESL. Oral tablet formulations of either 400 or 800 mg ESL from the new API source were found to be bioequivalent to the corresponding marketed Zebinix® formulation according to the regulatory definition of bioequivalence.

  7. Bioequivalence of generic lamotrigine 100-mg tablets in healthy Thai male volunteers: a randomized, single-dose, two-period, two-sequence crossover study.

    Science.gov (United States)

    Srichaiya, Arunee; Longchoopol, Chaowanee; Oo-Puthinan, Sarawut; Sayasathid, Jarun; Sripalakit, Pattana; Viyoch, Jarupa

    2008-10-01

    Lamotrigine is an antiepileptic drug which has been used in the treatment of epilepsy and bipolar disorder. A search of the literature did not find previously published bioequivalence and pharmacokinetic evaluations of lamotrigine in healthy Thai male volunteers. The aim of this study was to compare the pharmacokinetic parameters between 2 brands of lamotrigine in healthy Thai male volunteers. A randomized, single-dose, 2-period, 2-sequence, crossover study design with a 2-week washout period was conducted in healthy Thai males. Subjects were randomized to receive either the test or reference formulation in the first period. All subjects were required to be nonsmokers and without a history of alcohol or drug abuse. Plasma samples were collected over a 120-hour period after 100-mg lamotrigine administration in each period. A validated high-performance liquid chromatography ultraviolet method was used to analyze lamotrigine concentration in plasma. Pharmacokinetic parameters were determined using a noncompartmental method. Bioequivalence between the test and reference products, as defined by the US Food and Drug Administration (FDA), is determined when the ratio for the 90% CIs of the difference in the means of the log-transformed AUC(0-t), AUC(0-infinity), and C(max) of the 2 products are within 0.80 and 1.25. Adverse events were determined by measuring vital signs after dosing. Subjects were also asked if they suffered from undesirable effects such as nausea, vomiting, dizziness, and headache. This bioequivalence study was performed in 24 healthy Thai males (mean [SD] age, 20.5 [1.3] years; range, 19-24 years; weight, 62.5 [7.4] kg; height, 172.8 [6.9] cm; body mass index, 20.9 [2.0] kg/m(2)). The mean (SD) C(max) and T(max) of the test formulation of lamotrigine were 1.7 (0.3) microg/mL and 1.2 (0.9) hours, respectively. The mean (SD) C(max) and T(max) of the reference formulation of lamotrigine were 1.7 (0.3) microg/mL and 1.4 (1.0) hours, respectively. The mean

  8. Teaching and assessing veterinary professionalism.

    Science.gov (United States)

    Mossop, Liz H; Cobb, Kate

    2013-01-01

    The teaching and assessment of professional behaviors and attitudes are important components of veterinary curricula. This article aims to outline some important considerations and concepts which will be useful for veterinary educators reviewing or developing this topic. A definition or framework of veterinary professionalism must be decided upon before educators can develop relevant learning outcomes. The interface between ethics and professionalism should be considered, and both clinicians and ethicists should deliver professionalism teaching. The influence of the hidden curriculum on student development as professionals should also be discussed during curriculum planning because it has the potential to undermine a formal curriculum of professionalism. There are several learning theories that have relevance to the teaching and learning of professionalism; situated learning theory, social cognitive theory, adult learning theory, reflective practice and experiential learning, and social constructivism must all be considered as a curriculum is designed. Delivery methods to teach professionalism are diverse, but the teaching of reflective skills and the use of early clinical experience to deliver valid learning opportunities are essential. Curricula should be longitudinal and integrated with other aspects of teaching and learning. Professionalism should also be assessed, and a wide range of methods have the potential to do so, including multisource feedback and portfolios. Validity, reliability, and feasibility are all important considerations. The above outlined approach to the teaching and assessment of professionalism will help ensure that institutions produce graduates who are ready for the workplace.

  9. Liver scintigraphy in veterinary medicine.

    Science.gov (United States)

    Morandi, Federica

    2014-01-01

    The most common veterinary application of liver scintigraphy is for the diagnosis of portosystemic shunts (PSSs). There has been a continual evolution of nuclear medicine techniques for diagnosis of PSS, starting in the early 1980s. Currently, transplenic portal scintigraphy using pertechnetate or (99m)Tc-mebrofenin is the technique of choice. This technique provides both anatomical and functional information about the nature of the PSS, with high sensitivity and specificity. Hepatobiliary scintigraphy has also been used in veterinary medicine for the evaluation of liver function and biliary patency. Hepatobiliary scintigraphy provides information about biliary patency that complements finding in ultrasound, which may not be able to differentiate between biliary ductal dilation from previous obstruction vs current obstruction. Hepatocellular function can also be determined by deconvolutional analysis of hepatic uptake or by measuring the clearance of the radiopharmaceutical from the plasma. Plasma clearance of the radiopharmaceutical can be directly measured from serial plasma samples, as in the horse, or by measuring changes in cardiac blood pool activity by region of interest analysis of images. The objective of this paper is to present a summary of the reported applications of hepatobiliary scintigraphy in veterinary medicine. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Strategies That Delay Market Entry of Generic Drugs.

    Science.gov (United States)

    Vokinger, Kerstin Noëlle; Kesselheim, Aaron S; Avorn, Jerry; Sarpatwari, Ameet

    2017-09-18

    Increasing prescription drug expenditures in the United States are primarily driven by high brand-name drug prices. Although generic competition helps lower drug prices, manufacturers of brand-name drugs often work to delay the availability of generic versions of their products. Strategies to forestall generic competition include patenting peripheral aspects of a drug or modified formulations that do not add clinical value, paying generic manufacturers to settle lawsuits challenging the validity of patents on brand-name drugs ("reverse payment" settlements), denying generic manufacturers access to drug samples necessary for bioequivalence testing, misusing risk evaluation and mitigation strategies, and filing citizen petitions with the US Food and Drug Administration (FDA). To address such tactics, the federal government can interpret existing patenting standards more strictly and promote certain types of patent challenges to ensure that patents are granted or upheld only for true innovations. Congress can enact pending legislation that would help discourage reverse payment settlements and compel brand-name manufacturers to share drug samples for bioequivalence testing. Finally, the FDA can provide earlier guidance on bioequivalence determinations for complex generic products and adopt the presumption that late-filed citizen petitions should be summarily rejected.

  11. Pharmacokinetic and bioequivalence comparison of a single 100-mg dose of cefteram pivoxil powder suspension and tablet formulations: a randomized-sequence, open-label, two-period crossover study in healthy Chinese adult male volunteers.

    Science.gov (United States)

    Zou, Jianjun; Di, Bin; Wu, Chun Yong; Hu, Qin; Li, Jian Hua; Zhu, Yubing; Fan, Hongwei; Xiao, DaWei; Wang, Guang Ji

    2008-04-01

    Cefteram pivoxil (CFTM-PI) is an oral antibiotic available in powder suspension and tablet formulations indicated in China for the treatment of bacterial infections. Although these 2 formulations are marketed in China, published information regarding their pharmacokinetics and bioequivalence in the Chinese population is not available. The aim of this study was to compare the pharmacokinetics and bioequivalence of the powder suspension (test) and tablet (reference) formulations of CFTM-PI 100 mg available in China. This single-dose, randomized-sequence, open-label, 2-period crossover study was performed at the Nanjing First Hospital of Nanjing Medical University. Eligible subjects were healthy male volunteers who were randomly assigned at a 1:1 ratio to receive a single 100-mg dose of the test or reference formulation, followed by a 1-week washout period and administration of the alternate formulation. The study drugs were administered after a 12-hour overnight fast. Plasma was assayed using a high-performance liquid chromatography method. For analysis of pharmacokinetic properties, including C(max), AUC from time 0 (baseline) to 6 hours (AUC(0-6)), and AUC from baseline to infinity (AUC(0-infinity)), blood samples were obtained at intervals over the 6-hour period after study drug administration. The formulations were considered bioequivalent if the log-transformed ratios of C(max) and AUC were within the predetermined equivalence range (80%-125%) as established by the US Food and Drug Administration (FDA). Tolerability was assessed by monitoring vital signs and laboratory tests (hematology, blood biochemistry, hepatic function, and urinalysis), and by questioning subjects about adverse events (AEs). Twenty-four Chinese male subjects (mean [range] age,24.2 [23-32] years;weight,64.3 [58-67] kg; height, 172 [167-185] cm) enrolled; all completed the study. No period or sequence effect was observed. The 90% CIs for the log-transformed ratios of C(max), AUC(0-6;), and

  12. Evaluation of the bioequivalence of capsules containing 150 mg of fluconazole.

    Science.gov (United States)

    Porta, V; Chang, K H; Storpirtis, S

    2005-01-06

    Fluconazole is an antifungal agent. The purpose of this study was to evaluate bioequivalence of two commercial 150 mg capsule formulations of fluconazole available in the Brazilian market. The study was an open, randomized, two-period, two-group crossover trial with a 2-week washout interval. Blood samples were collected throughout a 96-h period after administration of reference product (R) and test product (T) to 28 fasting volunteers. A simple, accurate, precise and sensitive high-performance liquid chromatographic (HPLC) method with ultraviolet detection was developed and validated for quantification of fluconazole in plasma samples after liquid-liquid extraction. Bioequivalence between the products was determined by calculating 90% confidence intervals (90% C.I.) for the ratio of C(max), AUC(0-t) and AUC(0-infinity) values for the test and reference products, using logarithmic transformed data. The 90% confidence intervals for the ratio of C(max) (101.06-105.45%), AUC(0-t) (97.11-104.69%) and AUC(0-infinity) (97.96-103.36%) values for the test and reference products are within the 80-125% interval, proposed by FDA and EMEA. It was concluded that the two fluconazole formulations are bioequivalent in their rate and extent of absorption.

  13. Tests for bioequivalence of control media and test media in studies of toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Erickson, W.P.; McDonald, L.L. [Western EcoSystems Technology, Inc., Cheyenne, WY (United States)

    1995-07-01

    Statistical tests of the classical (null) hypothesis--that there is no difference in effects of control media and tested--are commonly used to make statistical inferences toward the no-observed-adverse-effect concentration. However, failing to rejects this hypothesis is not considered as scientific proof the hypothesis is true. An effect may exist, but high variation due to inadequate replication, variation in experimental units, or imprecise measurement techniques may yield data for which the hypothesis is not rejected. An experiment may also be too precise, yielding effects that are statistically significant but not biologically important. The authors propose the use of tests of bioequivalence of control media and test media to alleviate these unsatisfactory characteristics of tests and of the classical hypotheses for regulatory decisions. They review and illustrate the test for bioequivalence using acute and chronic toxicity data. They also define a procedure for determining the level of effect at which there will be high power to refute the hypothesis that there is a lack of bioequivalence if in fact the biological response in the control media is identical to the responses in the test media.

  14. Bioequivalence study with lapatinib powder for oral suspension and the original tablet formulation in cancer patients.

    Science.gov (United States)

    Koch, Kevin M; Ferron-Brady, Geraldine; Lemmon, Colleen; Cartee, Leanne; Hollyfield, Hedy; D'Amelio, Anthony M; Piepszak, Alexandra; Swaby, Ramona F; Curran, David; Arya, Niki

    2015-01-01

    Lapatinib is approved for use in various therapeutic combinations for treating metastatic breast cancers that over-express HER2. To deliver the approved doses, up to six large tablets need to be ingested with the current 250-mg tablets. For ease of ingestion, a powder for oral suspension was developed. This study was an open-label, randomized, adaptive design, two-period crossover bioequivalence study of the powder for suspension relative to the commercial tablet at steady state following once daily dosing for 7 days in patients with advanced cancer. To minimize the number of cancer patients required for a pivotal bioequivalence study (144 in this case), a four-stage adaptive group sequential design with interim analyses after every 36 subjects was implemented to allow for early termination. Bioequivalence for the oral suspension relative to the commercial tablet was demonstrated in both the first (and only) interim analysis and the final analysis, as the 90% confidence intervals for the treatment comparison ratios for both AUC0-24 and Cmax were contained within the acceptance criteria (0.80, 1.25). Additionally, there was no statistical difference in tlag or tmax , suggesting no difference in the absorption rate between treatments. There were no unexpected safety findings during this study. © 2014, The American College of Clinical Pharmacology.

  15. Overview of suspected adverse reactions to veterinary medicinal products reported in South Africa (March 2002 – February 2003

    Directory of Open Access Journals (Sweden)

    V. Naidoo

    2003-07-01

    Full Text Available The Veterinary Pharmacovigilance and Medicines Information Centre is responsible for the monitoring of veterinary adverse drug reactions in South Africa. An overview of reports of suspected adverse drug reactions received by the centre during the period March 2002 to February 2003 is given. In total, 40 reports were received. This had declined from the previous year. Most reports involved suspected adverse reactions that occurred in dogs and cats. Most of the products implicated were Stock Remedies. The animal owner predominantly administered these products. Only 1 report was received from a veterinary pharmaceutical company. Increasing numbers of reports are being received from veterinarians.

  16. Drug: D10032 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D10032 Drug Tylvalosin (USAN/INN) C53H87NO19 1041.5872 1042.2532 D10032.gif Veterinary...hibitor 23S rRNA of 50S ribosomal subunit inhibitor [KO:K01980] Macrolides Tylvalosin; Veterinary

  17. Drug: D08391 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D08391 Drug Pirlimycin (INN); Pirsue [veterinary] (TN) ... C17H31ClN2O5S D08391.gif ... ... ... Antibacterial ... DG01578 ... Lincosamide antibiotic Chemical group: DG01577 ... Lincosamide Target: 50S ribosomal subunit (veterinary

  18. Drug: D03867 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D03867 Drug Dirlotapide (USAN/INN); Slentrol [veterinary] (TN) ... C40H33F3N4O3 D0386...7.gif ... Not for use in humans. veterinary medicine - Treatment of obesity in companion animals (dogs) M

  19. Drug: D02601 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D02601 Drug Phenothiazine (INN); Thiodiphenylamin; Nemazine [veterinary] (TN) ... C12...H9NS D02601.gif ... veterinary medicine ... CAS: 92-84-2 PubChem: 17396771 ChEMBL: CHEMBL828 LigandBox: D02601 NIKKAJI: J3.932B ...

  20. Drug: D07730 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D07730 Drug Cloprostenol (INN); Dalmazin [veterinary] (TN) ... C22H29ClO6 D07730.gif ... ... Prostaglandin derivative veterinary medicine ... CAS: 40665-92-7 PubChem: 51092026 LigandBox: D07730 NIKKAJI: J299.284A ...

  1. Drug: D10034 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D10034 Drug Tylvalosin tartrate (USAN); Aiviosin [veterinary] (TN) ... C53H87NO19. (C... 50S ribosomal subunit (veterinary) ... CAS: 63428-13-7 PubChem: 135626754 LigandBox: D10034 ... ... and porcine proliferative enteropathy caused by Lawsonia intracellularis Target:

  2. Drug: D08211 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D08211 Drug Metomidate hydrochloride; Hypnodil [veterinary] (TN) C13H14N2O2. HCl 26...6.0822 266.7234 D08211.gif Hypnotic, sedative [veterinary] CAS: 35944-74-2 PubChem: 96024899 LigandBox: D082

  3. Drug: D07964 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D07964 Drug Fluazuron (INN); Acatak Pour-ON (TN) [veterinary] C20H10Cl2F5N3O3 505.0...019 506.2097 D07964.gif Insecticide [veterinary] insect growth regulator (chitin synthesis inhibitor) CAS: 8

  4. Drug: D05084 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D05084 Drug Moxidectin (USAN/INN) C37H53NO8 639.3771 639.8186 D05084.gif Antiparasitic [veterinary] veterina...ry medicine CAS: 113507-06-5 PubChem: 47206811 LigandBox: D05084 NIKKAJI: J481.172K

  5. Drug: D08034 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D08034 Drug Halofuginone (INN); Halocur [veterinary] (TN) C16H17BrClN3O3 413.0142 4...14.6815 D08034.gif Antiprotozoal, coccidiocidal [veterinary] Febrifugine [CPD:C10677] derivative glutamyl-pr

  6. Drug: D08178 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D08178 Drug Menbutone (INN); Genabiline [veterinary] (TN) C15H14O4 258.0892 258.269...3 D08178.gif Choleretic veterinary medicine CAS: 3562-99-0 PubChem: 96024868 LigandBox: D08178 NIKKAJI: J8.1

  7. Drug: D04140 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D04140 Drug Fenbendazole (USP/INN); Panacur [veterinary] (TN) C15H13N3O2S 299.0728 ...299.3476 D04140.gif Anthelmintic ATC code: P02CA06 veterinary medicine Anatomical Therapeutic Chemical (ATC)

  8. Drug: D05813 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D05813 Drug Selamectin (USAN/INN) C43H63NO11 769.4401 769.9604 D05813.gif Antiparasitic [veterinary] veterin...ary medicine CAS: 165108-07-6 PubChem: 47207474 LigandBox: D05813 ATOM 55 1 C1z C 2

  9. Drug: D08455 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D08455 Drug Pyriproxyfen; Cyclio [veterinary] (TN) C20H19NO3 321.1365 321.3698 D084...55.gif Antiparasitic Same as: C18605 veterinary medicine CAS: 95737-68-1 PubChem: 96025141 LigandBox: D08455

  10. Drug: D07795 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D07795 Drug Detomidine (INN) C12H14N2 186.1157 186.253 D07795.gif Analgesic [veterinary...]; Hypnotic, sedative [veterinary] alpha2-adrenergic receptor agonist [HSA:150 151 152] [KO:K04138 K0413

  11. Drug: D05076 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D05076 Drug Morantel tartrate (USP) C12H16N2S. C4H6O6 370.1199 370.4207 D05076.gif Anthelmintic [veterinary...] veterinary medicine nicotinic cholinergic receptor alpha3beta2 enhancer [KO:K04805

  12. Drug: D08200 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D08200 Drug Methoprene (INN); Zodiac [veterinary] (TN) C19H34O3 310.2508 310.4715 D...08200.gif Insecticide; Pediculocide Same as: C14308 veterinary medicine juvenile hormone [CPD:C19613 C04867

  13. Drug: D07829 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D07829 Drug Diflubenzuron C14H9ClF2N2O2 310.0321 310.6833 D07829.gif Insecticide [veterinary...] Same as: C14427 veterinary medicine CAS: 35367-38-5 PubChem: 96024526 LigandBox: D07829 NIKKAJI:

  14. Drug: D08156 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D08156 Drug Marbofloxacin (INN); Marbocyl (TN) C17H19FN4O4 362.139 362.3556 D08156.gif Antibiotic [veterinar...y] veterinary medicine CAS: 115550-35-1 PubChem: 96024846 LigandBox: D08156 NIKKAJI

  15. Bioequivalence of generic alendronate sodium tablets (70 mg to Fosamax® tablets (70 mg in fasting, healthy volunteers: a randomized, open-label, three-way, reference-replicated crossover study

    Directory of Open Access Journals (Sweden)

    Zhang Y

    2017-07-01

    Full Text Available Yifan Zhang,1 Xiaoyan Chen,1 Yunbiao Tang,2 Youming Lu,1 Lixia Guo,1 Dafang Zhong1 1State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 2Department of Pharmacy, The General Hospital of Shenyang Military Region, Shenyang, People’s Republic of China Purpose: The aim of this study was to evaluate the bioequivalence of a generic product 70 mg alendronate sodium tablets with the reference product Fosamax® 70 mg tablet. Materials and methods: A single-center, open-label, randomized, three-period, three-sequence, reference-replicated crossover study was performed in 36 healthy Chinese male volunteers under fasting conditions. In each study period, the volunteers received a single oral dose of the generic or reference product (70 mg. Blood samples were collected at pre-dose and up to 8 h after administration. The bioequivalence of the generic product to the reference product was assessed using the US Food and Drug Administration (FDA and European Medicines Agency (EMA reference-scaled average bioequivalence (RSABE methods. Results: The average maximum concentrations (Cmax of alendronic acid were 64.78±43.76, 56.62±31.95, and 60.15±37.12 ng/mL after the single dose of the generic product and the first and second doses of the reference product, respectively. The areas under the plasma concentration–time curves from time 0 to the last timepoint (AUC0–t were 150.36±82.90, 148.15±85.97, and 167.11±110.87 h·ng/mL, respectively. Reference scaling was used because the within-subject standard deviations of the reference product (sWR for Cmax and AUC0–t were all higher than the cutoff value of 0.294. The 95% upper confidence bounds were -0.16 and -0.17 for Cmax and AUC0–t, respectively, and the point estimates for the generic/reference product ratio were 1.08 and 1.00, which satisfied the RSABE acceptance criteria of the FDA. The 90% CIs for Cmax and AUC0–t were 90.35%–129

  16. Bioequivalence and pharmacokinetics of two zidovudine formulations in healthy Brazilian volunteers: an open-label, randomized, single-dose, two-way crossover study.

    Science.gov (United States)

    Dos Reis Serra, Cristina Helena; Mori Koono, Eunice Emiko; Kano, Eunice Kazue; Schramm, Simone Grigoleto; Armando, Yara Popst; Porta, Valentina

    2008-05-01

    Zidovudine is a thymidine nucleoside reverse transcriptase inhibitor with activity against HIV type 1. Some (approximately 8) generic formulations of zidovudine are available in Brazil; however, based on a literature search, information concerning their bioavailability and pharmacokinetic properties in the Brazilian population has not been reported. The aim of this study was to compare the bioavailability and pharmacokinetic properties of 2 capsule formulations of zidovudine 100 mg in healthy Brazilian volunteers. This open-label, randomized, 2-way crossover study utilized a 1-week washout period between doses. Blood samples were collected for 8 hours after a single dose of zidovudine 100-mg test (Zidovudina, Fundação para o Remédio Popular, São Paulo, Brazil) or reference formulation (Retrovir, GlaxoSmithKline, Philadelphia, Pennsylvania). Plasma zidovudine concentrations were determined using a validated high-performance liquid chromatography method with ultraviolet detection at 265 nm. C(max), T(max), AUC(0-t), AUC(0-infinity), t(1/2), and the elimination constant (k(e)) were determined using noncompartmental analysis. The formulations were considered bioequivalent if the 90% CIs for C(max), AUC(0-t), and AUC(0-infinity) fell within the interval of 80% to 125%,the regulatory definition set by the US Food and Drug Administration (FDA). Twenty-four healthy volunteers (12 males, 12 females; mean age, 27 years; weight, 60 kg; height, 167 cm) were enrolled and completed the study. The 90% CIs of the treatment ratios for the logarithmic transformed values of C(max), AUC(max)0-t, and AUC(0-infinity) were 80.0% to 113.6%, 93.9% to 109.7%, and 93.6% to 110.1%, respectively. The values for the test and reference formulations were within the FDA bioequivalence definition intervals of 80% to 125%. In this small study in healthy subjects, no statistically significant differences in C(max), AUC(0-t), and AUC(0-infinity) were found between the test and reference

  17. Veterinary School Applicants: Financial Literacy and Behaviors.

    Science.gov (United States)

    Carr, McKensie M; Greenhill, Lisa M

    2015-01-01

    Each year the Association of American Veterinary Medical Colleges (AAVMC) conducts a survey after the close of the Veterinary Medical College Application Service (VMCAS) application. The survey provides a glimpse into applicant behavior surrounding the veterinary school application process. Additional survey questions probe into applicant financial behaviors, use of financial products and services, and pet ownership. This article examines the 2013 survey data from applicants who successfully completed the application, with a focus on applicant financial literacy and behaviors. Data from the study revealed a disconnect between applicants' perception of their ability to deal with day-to-day finances and their actual financial behaviors, particularly for first-generation college student applicants and applicants who are racially/ethnically underrepresented in veterinary medicine (URVM). Many applicants were not able to accurately report the average veterinary school graduate's student debt level, which suggests the potential need for better education about the costs associated with attending veterinary school.

  18. Welcome to Veterinary Medicine: Research and Reports

    Directory of Open Access Journals (Sweden)

    Musser JMB

    2011-09-01

    Full Text Available Musser Jeffrey MBDepartment of Veterinary Pathobiology, College of Veterinary Medicine, Texas A&M University, TX, USAThis year marks the 250th anniversary of the Royal Veterinary School in Lyon, France, the world's first veterinary college. Since its inception, many changes have occurred in veterinary medicine such as views on education and didactic learning, demographics of our profession, and standards of practice in animal husbandry, medicine, surgery, anesthesia, and vaccinology. In fact, the concept of infectious diseases has changed - remember the germ theory was proposed a mere 140 years ago. However, one constant tenet in our profession has been the need to disseminate progresses, innovations, advances, and developments in veterinary sciences. Published reports are the foundation for the growth of medicine and science. What would the state of medicine be if Pasteur, Koch, Bourgelat, or Theobald Smith had not published their works?

  19. Veterinary Business Management Association presents program to aid future growth and stability of veterinary profession

    OpenAIRE

    Douglas, Jeffrey S.

    2008-01-01

    Spiraling veterinary student debt and the lack of a sustainable and profitable business model for many private practices in the modern business environment threaten the future growth and stability of the veterinary profession.

  20. Primary care veterinary usage of systemic glucocorticoids in cats and dogs in three UK practices.

    Science.gov (United States)

    O'Neill, D; Hendricks, A; Summers, J; Brodbelt, D

    2012-04-01

    To describe systemic glucocorticoid usage in cats and dogs by three primary care -veterinary practices in England and to ascertain risk factors for clinical use. To evaluate consistency of prescribing patterns across clinics. To validate a merged database of primary veterinary clinical data as a functional tool for clinical epidemiological research. A merged database was established from clinical data on 31,273 cat and dog consultations with pharmacotherapy from three veterinary practices in England. Descriptive statistics described systemic glucocorticoid drug use in cats and dogs while mixed-effects logistic regression modelling evaluated risk factors. Individual clinic usage was compared. Overall, 1877 (16·68%) cat consultations and 2913 (14·55%) dog consultations resulted in systemic glucocorticoid therapy. Cats received higher parenteral (Pveterinary clinical database was effective for epidemiological research. © 2012 British Small Animal Veterinary Association.

  1. Pursuing a career in veterinary public health.

    Science.gov (United States)

    Radakovic, Milorad

    2015-11-14

    Milorad Radakovic is a teaching fellow in veterinary public health (VPH) at the University of Cambridge. Here, he explains why he believes the challenges in this field of veterinary medicine make for an exciting career path. In a second article to be published in Vet Record Careers next week, he will share some of his own experiences of working in this field. British Veterinary Association.

  2. Stress management interventions for veterinary students.

    Science.gov (United States)

    Gelberg, Susan; Gelberg, Howard

    2005-01-01

    Two-hundred-and-eighty-nine veterinary students from all four years of the University of Tennessee, College of Veterinary Medicine (UTCVM) were invited to complete the Derogatis Stress Profile (DSP)1 and an original Demographic Data Profile (DDP). The DSP assessed the students' current experiences of perceived stress, and the DDP was designed to gather information about students' academic year, their living situations, their financial situations, their interest area within the veterinary medical profession, and their current methods of coping with stress. These data were gathered as a baseline measure of veterinary medical students' perceived level of stress and quality of life. In an earlier study, data were also collected from faculty and staff about the perceived quality of the climate and culture of the veterinary college. The results of the DSP and DDP suggest that, although veterinary students at UTCVM do not experience significant levels of stress overall, they do report higher levels of subjective stress, time pressure, and depression than the general population. The more companion animals that veterinary students cared for in their personal lives, the more likely they were to report higher levels of perceived stress. Lastly, there were significant differences between genders, with female veterinary students reporting higher levels of perceived stress than their male counterparts. The preliminary results of the climate and culture data suggest that faculty and staff of the veterinary college individually feel that they are cared for in the work environment and collectively believe that the college strives for excellence.

  3. Privatizing community animal health worker based veterinary ...

    African Journals Online (AJOL)

    Privatizing community animal health worker based veterinary services delivery system in West Kordofan, Southern Sudan; The needed roles of community animal health assistant (CAHA) and Pastoral unions.

  4. Clinical features and management of equine post operative ileus (POI): Survey of Diplomates of the American Colleges of Veterinary Internal Medicine (ACVIM), Veterinary Surgeons (ACVS) and Veterinary Emergency and Critical Care (ACVECC).

    Science.gov (United States)

    Lefebvre, D; Hudson, N P H; Elce, Y A; Blikslager, A; Divers, T J; Handel, I G; Tremaine, W H; Pirie, R S

    2016-11-01

    A recent survey of European Colleges (European College of Equine Internal Medicine [ECEIM] and European College of Veterinary Surgeons [ECVS]) revealed the different strategies implemented by, and some of the challenges facing, European clinicians presented with cases of post operative ileus (POI). It was concluded that further comparative analysis of opinions, canvassed from additional colleges of equine veterinary specialism worldwide, would provide valuable additional insight into current POI knowledge on a more global scale. To report and compare the current strategies favoured by American veterinary specialists when managing POI in horses that underwent emergency colic surgery. Cross-sectional survey. Electronic invitations were sent to 814 Large Animal specialists, including 3 colleges: the American College of Veterinary Internal Medicine (ACVIM), American College of Veterinary Surgeons (ACVS) and the American College of Veterinary Emergency and Critical Care (ACVECC). The response rate was 14% (115/814). The majority of respondents (68%) reported an estimated prevalence range of POI of 0-20%. The presence of reflux on nasogastric intubation was the main criterion used to define POI. A lesion involving the small intestine was considered the main risk factor for POI. Anti-inflammatory drugs, intravenous (i.v.) fluids and antimicrobial drugs were the primary strategies used when managing POI. Flunixin meglumine and i.v. lidocaine were the drugs most commonly used in the treatment of horses with POI. Supplementary management strategies targeted mainly the prevention of post operative adhesions, infection and inflammation. There is a lack of consensus on the clinical definition of POI. Prospective and objective clinical assessment of the effectiveness of the different strategies contained within this and the European survey is necessary in order to identify a standardised approach to the management of equine POI. © 2015 EVJ Ltd.

  5. A rapid and sensitive HPLC method for the analysis of metronidazole in human plasma: application to single dose pharmacokinetic and bioequivalence studies

    Directory of Open Access Journals (Sweden)

    Jaber Emami

    2006-03-01

    Full Text Available A sensitive, accurate and rapid reverse phase HPLC method was developed to quantitate plasma levels of metronidazole in order to conduct a comparative bioavailability studies. The drug and internal standard were added to plasma samples, vortexed and then zinc sulfate solution was added in order to precipitate the plasma proteins. Samples were centrifuged at 3000 rpm for 10 min. The supernatant layer was separated and analyzed on a phenyl (300 × 4.6mm column, with 5% acetonitrile in 0.1 M KH2PO4 buffer (pH = 4.5 at 324 nm. The standard curve covering 0.15 – 30 μg/ml concentration range, was linear (r2 = 0.9999, relative errors were within 2.48 to 9.15 % and the CV% ranged from 2.999 to 10.796. The method is suitable for bioavailability, pharmacokinetic, and bioequivalent studies in human. The in-vivo study was carried out in 12 healthy volunteers according to a single dose, two-sequence, cross over randomized design. The bioavailability was compared using the total area under the plasma level versus time curve (AUC0-48, AUC0-, peak plasma concentration (Cmax and time to Cmax (Tmax. No statistically significant difference was found between the AUC0- , Cmax and Tmax values of the test and reference, Flagyl® (p > 0.05. The 90% CI for the ratio of the AUC0- (0.94-1.07 and Cmax (0.88-1.03 and the logarithmically transformed AUC0- (0.99-1.01 and Cmax (0.94-1.01 values of the generic product over those of Flagyl® was calculated to be within the acceptable limit of 0.80-1.20 and 0.80-1.25, respectively. It was, therefore, concluded that the generic metronidazole was bioequivalent with the innovator formulation.

  6. Randomized two-way cross-over bioequivalence study of two amoxicillin formulations and inter-ethnicity pharmacokinetic variation in healthy Malay volunteers.

    Science.gov (United States)

    Liew, Kai Bin; Loh, Gabriel Onn Kit; Tan, Yvonne Tze Fung; Peh, Kok Khiang

    2014-09-01

    The objectives of this study were to develop a new deproteinization method to extract amoxicillin from human plasma and evaluate the inter-ethnic variation of amoxicillin pharmacokinetics in healthy Malay volunteers. A single-dose, randomized, fasting, two-period, two-treatment, two-sequence crossover, open-label bioequivalence study was conducted in 18 healthy Malay adult male volunteers, with one week washout period. The drug concentration in the sample was analyzed using high-performance liquid chromatography (UV-vis HPLC). The mean (standard deviation) pharmacokinetic parameter results of Moxilen® were: peak concentration (Cmax ), 6.72 (1.56) µg/mL; area under the concentration-time graph (AUC0-8 ), 17.79 (4.29) µg/mL h; AUC0-∞ , 18.84 (4.62) µg/mL h. Those of YSP Amoxicillin® capsule were: Cmax , 6.69 (1.44) µg/mL; AUC0-8 , 18.69 (3.78) µg/mL h; AUC00-∞ , 19.95 (3.81) µg/mL h. The 90% confidence intervals for the logarithmic transformed Cmax , AUC0-8 and AUC0-∞ of Moxilen® vs YSP Amoxicillin® capsule was between 0.80 and 1.25. Both Cmax and AUC met the predetermined criteria for assuming bioequivalence. Both formulations were well tolerated. The results showed significant inter-ethnicity variation in pharmacokinetics of amoxicillin. The Cmax and AUC of amoxicillin in Malay population were slightly lower compared with other populations. Copyright © 2014 John Wiley & Sons, Ltd.

  7. 78 FR 23742 - Nomination Form of Veterinary Shortage Situations for the Veterinary Medicine Loan Repayment...

    Science.gov (United States)

    2013-04-22

    ... National Institute of Food and Agriculture Nomination Form of Veterinary Shortage Situations for the Veterinary Medicine Loan Repayment Program (VMLRP) AGENCY: National Institute of Food and Agriculture, USDA... Act of 1995, invites the general public to comment on an information collection for the Veterinary...

  8. Opinions of Veterinary Medical Educators Towards the Problems and Needs of Veterinary Medical Education

    Science.gov (United States)

    Sisk, Dudley B.; And Others

    1976-01-01

    Members of the American Association of Veterinary Medical Colleges-Council of Educators were surveyed in an attempt to measure their opinions and feelings towards veterinary medical education. Their opinions on such topics as relationships between students, faculty, the curriculum, and the identity of veterinary medicine are reported. (LBH)

  9. The toxicity effect of selected drugs in animals

    OpenAIRE

    HUNCHAK V.M.; HUFRIY D.F.; MASLIANKO R.P.; HUTІY B.V.; LEVKIVSKY D.M.; LEVKIVSKA N.D.; STORCHAK Y.G.

    2014-01-01

    Therapeutic products quite often are causes of poisoning in both small and large animals. Drug poisonings in animals occur commonly due to off-label use of medicines, wrong dosage, negligence, accidental ingestion and deliberate poisonings. Toxicity of veterinary drugs may become evident also in therapeutic doses when adverse effects may occur. The aim of this review is to inform veterinary specialists about both veterinary and human drugs, specifically antiparasitics, non-steroidal anti-infl...

  10. Therapeutic laser in veterinary medicine.

    Science.gov (United States)

    Pryor, Brian; Millis, Darryl L

    2015-01-01

    Laser therapy is an increasingly studied modality that can be a valuable tool for veterinary practitioners. Mechanisms of action have been studied and identified for the reduction of pain and inflammation and healing of tissue. Understanding the basics of light penetration into tissue allows evaluation of the correct dosage to deliver for the appropriate condition, and for a particular patient based on physical properties. New applications are being studied for some of the most challenging health conditions and this field will continue to grow. Additional clinical studies are still needed and collaboration is encouraged for all practitioners using this technology. Copyright © 2015. Published by Elsevier Inc.

  11. Introduction to veterinary clinical oncology

    Energy Technology Data Exchange (ETDEWEB)

    Weller, R.E.

    1991-10-01

    Veterinary clinical oncology involves a multidisciplinary approach to the recognition and management of spontaneously occurring neoplasms of domestic animals. This requires some knowledge of the causes, incidence, and natural course of malignant disease as it occurs in domestic species. The purpose of this course is to acquaint you with the more common neoplastic problems you will encounter in practice, so that you can offer your clients an informed opinion regarding prognosis and possible therapeutic modalities. A major thrust will be directed toward discussing and encouraging treatment/management of malignant disease. Multimodality therapy will be stressed. 10 refs., 3 tabs.

  12. [New concepts in human oncology: is it possible to use them in veterinary medicine as well?].

    Science.gov (United States)

    Marconato, L; Ruess-Melzer, K; Buchholz, J; Kaser-Hotz, B

    2011-08-01

    In human oncology, novel targeted therapy focusing on monoclonal antibodies and tyrosine kinase inhibitors has become an attractive anticancer strategy. The introduction of antiangiogenetic drugs and metronomic chemotherapy has also increased the therapeutic arsenal. Chemotherapy still plays a key role in the treatment of many tumors affecting dogs and cats. However, novel anticancer strategies (including tyrosine kinase inhibitors and monoclonal antibodies, as well as antiangiogenetic treatments) are becoming relevant in veterinary medicine, too. The goal of this review is to describe new therapeutic strategies for cancer treatment in veterinary medicine, including less well-known chemotherapeutic drugs.

  13. Veterinary Preventive Medicine Curriculum Development at Louisiana State University

    Science.gov (United States)

    Hubbert, William T.

    1976-01-01

    The program aims at training veterinarians, with interdepartmental faculty participation the rule rather than the exception. Included in the curriculum are: avian medicine, herd health management, veterinary public health, veterinary food hygiene, and regulatory veterinary medicine. (LBH)

  14. [New drugs for horses and production animals in 2012].

    Science.gov (United States)

    Emmerich, I U

    2013-01-01

    In 2012, two newly developed active pharmaceutical ingredients for horses and food producing animals were released on the German market for veterinary drug products. Those are the parenterally applicable first generation cephalosporin Cefalonium (Cepravin®) and the nonsteroidal anti-inflammatory drug Suxibuzone (Danilon®). Furthermore, one established veterinary active pharmaceutical ingredient is applicable to additional species: The anticoccidial Amprolium (Eimeryl®) has again been authorized for chicken and turkeys. Additionally, two veterinary drugs with a new formulation as well as three products with a new strength and one product with a new indication have recently been released to the veterinary drugs market for horses and food producing animals.

  15. Applications of informatics in veterinary medicine

    Science.gov (United States)

    Smith, Ronald D.; Williams, Mitsuko

    2000-01-01

    This study used the peer-reviewed biomedical literature to define the veterinary informatics knowledgebase and associated subspecialties, and assesses the level of activity in the field over the thirty-year period from 1966 through 1995. Grateful Med was used to search the MEDLINE bibliographic database for articles that shared one or more Medical Subject Headings (MeSH) keywords from the veterinary and medical informatics subject headings. Each of ninety-five MeSH medical informatics terms was assigned to one of twelve veterinary informatics subspecialties. The number of articles retrieved by each MeSH keyword and subspecialty was calculated. A total of 611 articles were retrieved, representing the contributions of 1,338 authors published in 153 journals. The field experienced slow growth over the twenty-year period from 1966 through 1985. In the following decade, the cumulative number of veterinary informatics articles almost tripled and the percentage of veterinary-related articles that included an informatics component increased almost two-and-one-half fold. Despite this recent growth, the number of veterinary-related articles with an informatics component has never exceeded 1% of either the veterinary or medical informatics literature over the past thirty years, and representation of veterinary subspecialties in the literature varied widely. PMID:10658963

  16. Computer applications in veterinary medicine | Hassan | Nigerian ...

    African Journals Online (AJOL)

    ... diagnostic imaging and laboratory evaluations of specimens. Computers have also crept into the field of agro-veterinary consultancy services and have been useful here for clinical consultancy; agro-veterinary project design, monitoring and implementation; preparation of presentations as resource persons or instructor; ...

  17. Veterinary Safety's Conflicts in the EAEU

    Science.gov (United States)

    Kalymbek, Bakytzhan; Shulanbekova, Gulmira K.; Madiyarova, Ainur S.; Mirambaeva, Gulnaz Zh.

    2016-01-01

    This article is devoted to the problem of veterinary safety of the countries under the Eurasian Economic Union. Animal health's measures are provided in order to prevent the entry and spread of infectious animal diseases, including common to humans and animals, as well as goods not conforming to the common veterinary and sanitary requirements.…

  18. Operational modes of providing linkage between veterinary ...

    African Journals Online (AJOL)

    The study was conducted to. (1) determine the kinds of veterinary extension services that are provided to livestock farmers;. (2) determine the frequency of farmers contact with extension agents in relation to the extent of adoption of animal health innovations, and. (3) identify the various constraints to veterinary extension ...

  19. 9 CFR 3.110 - Veterinary care.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Veterinary care. 3.110 Section 3.110... WELFARE STANDARDS Specifications for the Humane Handling, Care, Treatment, and Transportation of Marine Mammals Animal Health and Husbandry Standards § 3.110 Veterinary care. (a) Newly acquired marine mammals...

  20. Staying current by searching the veterinary literature.

    Science.gov (United States)

    Buchanan, Robert A; Wooldridge, Anne A

    2011-01-01

    The body of knowledge in veterinary medicine and the biomedical sciences continues to grow logarithmically, and learning about new developments in veterinary medicine requires successful navigation of recently published literature worldwide. This article examines how veterinarians can use different types of automated services from databases and publishers to search the current and past literature, access articles, and manage references that are found.