Pharmaceutical Preparations Commons^™

Examining The Role Of Menthol Cigarettes In Progression To Established T Smoking Among Youth, James Nonnemaker, Shari P. Feirman, Anna Macmonegle, Bridget K. Ambrose, Kia J. Jackson, Megan J. Schroeder, Alexandria A. Smith, William Ridgeway, Olga Rass

United States Food and Drug Administration: Publications

Background: Menthol, a flavoring compound added to cigarettes, makes cigarettes more appealing to youth and inexperienced smokers and increases cigarettes' abuse liability. However, limited studies are available on menthol's role in smoking progression.

Methods: To assess the association between menthol in cigarettes and progression to established smoking, we used five waves of data from the Evaluation of Public Education Campaign on Teen Tobacco Cohort Study, a nationally representative longitudinal survey of U.S. youth conducted as part of “The Real Cost” evaluation. We used discrete time survival analysis to model the occurrence of two event outcomes—progression to established, current smoking and …

U.S. Adult Perceptions Of The Harmfulness Of Tobacco Products: Descriptive T Findings From The 2013–14 Baseline Wave 1 Of The Path Study, Geoffrey T. Fong, Tara Elton-Marshall, Pete Driezen, Annette R. Kaufman, K. Michael Cummings, Kelvin Choi, Jonathan Kwan, Amber Koblitz, Andrew Hyland, Maansi Bansal-Travers, Charles Carusi, Mary E. Thompson

United States Food and Drug Administration: Publications

Introduction: This study is the first nationally representative survey of U.S. adults (18+) to examine perceptions of the relative harms of eight non-cigarette tobacco products.

Methods: Data are from Wave 1 of the Population Assessment of Tobacco and Health (PATH) Study Adult Questionnaire, a nationally representative study of 32,320 adults in the United States conducted from September 2013 to December 2014.

Results: 40.7% of adults believed that electronic cigarettes were less harmful than cigarettes, and 17.8% of adults believed that hookah was less harmful than cigarettes. Those less knowledgeable about the health risks of smoking were more likely to believe …

Use Of Beta-Antagonists Or Hmg-Coa Reductase Inhibitors For Cardioprotection During Chemotherapy In Oncology Patients, Nicole Streich

Physician Assistant Scholarly Project Posters

Over the years, oncologists are better able to fight cancer and have increased cancer survival, but we are also finding that these lifesaving therapies can affect the heart and other parts of the body in a negative way. Chemotherapy is excellent at destroying cancer cells, but it also causes collateral damage to other healthy cells. There are certain chemotherapeutic agents that are known to cause cardiotoxicity. Currently we are monitoring the heart function of the patients who are receiving these cardiotoxic drugs prior to starting the chemotherapy as well as during and after treatment. However, there are currently no recommendations …

Can Nanotechnology Be The Leading Method In Detecting And Treating Cerebral Tumors?, Daniel D. Singh, Zuri Jules-Culver

OUR Journal: ODU Undergraduate Research Journal

Nanotechnology refers to the manipulation or design of materials and structures with desired features in the 1nm–1000 nm size range. The blood brain barrier (BBB) is a major obstacle that drugs must overcome in order to reach tumor cells. The role of this barrier is to transport essential nutrients while protecting and regulating the internal environment. Nanoparticles have been shown to transport drugs through this barrier and accumulate in tumor cells. This is significant since nanoparticles are drug carriers allowing chemotherapeutic drugs to accumulate in target areas (Sun et al., 2017). This is possible because they are able to be …

Development Of A Chemical Genetic Screen To Identify Compounds That Enhance Laromustine Cytotoxicity, Xiaoou Wang

Honors Theses

Laromustine is a chemotherapeutic sulfonylhydrazine prodrug used in clinical trials against acute myeloid leukemia. Though laromustine showed some success in clinical trials, more experiments are needed to understand the hematological toxicity and the molecular mechanisms of patients’ resistance. This project aims to develop a strategy to identify compounds synergistic with laromustine in cultured leukemia cells from a library of 450 FDA-approved compounds through a forward chemical genetic screen. To optimize the screen, the cell seeding density, doubling time, and dose response curves were determined. The optimized concentration of HL60 cells in these experiments was determined to be between 25,000 and …

The Impact Of Medical Marijuana On The Opioid Crisis, Carl David Eastep

Physician Assistant Scholarly Project Posters

• The opioid crisis dictates the need for research into alternative treatments for acute and chronic pain.

• Comprehensive literature review was conducted to determine if medical marijuana might play a role in the treatment of acute and chronic pain.

• The addiction profiles of medical marijuana and prescription opiates were compared along with the adverse effects and quality of life.

• No use for medical marijuana for the treatment of acute pain.

• Likely some benefits from medical marijuana for chronic pain.

• Addictive profile

• Marijuana – marijuana withdrawal syndrome.
• Prescription Opiates – highly addictive

• Adverse …

At Risk Alcohol Consumption With Smoking By National Background: Results From The Hispanic Community Health Study/Study Of Latinos, Frank C. Bandiera, Eliseo J. Pérez-Stable, Folefac Atem, Raul Caetano, Denise C. Vidot, Marc D. Gellman, Elena L. Navas-Nacher, Jianwen Cai, Gregory Talavera, Neil Schneiderman, Robert Kaplan

United States Food and Drug Administration: Publications

Introduction: Tobacco smoking and binge or excess drinking are unhealthy behaviors that frequently co-occur. Studies of Hispanics/Latinos have mostly been of Mexican Americans although there are substantial differences in smoking and drinking by heritage background. Associated with co-use by 5 subpopulations.

Methods: Cross-sectional data of 16,412 Hispanics/Latinos from Miami, the Bronx, Chicago and San Diego collected between 2008 and 2011 as part of the HCHS/SOL were analyzed. Smoking and alcohol consumption and demographic data were measured by self-report. Prevalence of smoking and alcohol consumption and co-use were reported. Logistic regression models examined the odds of co-use of smoking and binge …

Comparing Methods For Clinical Investigator Site Inspection Selection: A Comparison Of Site Selection Methods Of Investigators In Clinical Trials, Nicholas Hein, Elena Rantou, Paul Schuette

United States Food and Drug Administration: Publications

Background During the past two decades, the number and complexity of clinical trials have risen dramatically increasing the difficulty of choosing sites for inspection. FDA’s resources are limited and so sites should be chosen with care.

Purpose To determine if data mining techniques and/or unsupervised statistical monitoring can assist with the process of identifying potential clinical sites for inspection.

Methods Five summary-level clinical site datasets from four new drug applications (NDA) and one biologics license application (BLA), where the FDA had performed or had planned site inspections, were used. The num- ber of sites inspected and the results of the …

Mechanisms And Thermodynamics Of The Influence Of Solution-State Interactions Between Hpmc And Surfactants On Mixed Adsorption Onto Model Nanoparticles, Salin Gupta Patel

Theses and Dissertations--Pharmacy

Nanoparticulate drug delivery systems (NDDS) such as nanocrystals, nanosuspensions, solid-lipid nanoparticles often formulated for the bioavailability enhancement of poorly soluble drug candidates are stabilized by a mixture of excipients including surfactants and polymers. Most literature studies have focused on the interaction of excipients with the NDDS surfaces while ignoring the interaction of excipients in solution and the extent to which the solution-state interactions influence the affinity and capacity of adsorption. Mechanisms by which excipients stabilize NDDS and how this information can be utilized by formulators a priori to make a rational selection of excipients is not known.

The goals of …

Hematologic Safety Of Chronic Brain-Penetrating Erythropoietin Dosing In App/Ps1 Mice, Jiahong Sun, Joshua Yang, Kathrine Whitman, Charlene Zhu, David H. Cribbs, Ruben J. Boado, William M. Pardridge, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Introduction: Low blood-brain barrier (BBB) penetration and hematopoietic side effects limit the therapeutic development of erythropoietin (EPO) for Alzheimer's disease (AD). A fusion protein of EPO and a chimeric monoclonal antibody targeting the mouse transferrin receptor (cTfRMAb) has been engineered. The latter drives EPO into the brain via receptor-mediated transcytosis across the BBB and increases its peripheral clearance to reduce hematopoietic side effects of EPO. Our previous work shows the protective effects of this BBB-penetrating EPO in AD mice but hematologic effects have not been studied. Herein, we investigate the hematologic safety and therapeutic effects of chronic cTfRMAb-EPO dosing, …

An Open-Label, Single-Dose Study To Evaluate The Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Of Cinacalcet In Pediatric Subjects Aged 28 Days To < 6 Years With Chronic Kidney Disease Receiving Dialysis., Winnie Y. Sohn, Anthony A. Portale, Isidro B. Salusky, Hao Zhang, Lucy L. Yan, Bella Ertik, Shahnaz Shahinfar, Edward Lee, Bastian Dehmel, Bradley A. Warady

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Calcimimetics, shown to control biochemical parameters of secondary hyperparathyroidism (SHPT), have well-established safety and pharmacokinetic profiles in adult end-stage renal disease subjects treated with dialysis; however, such studies are limited in pediatric subjects.

METHODS: In this study, the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of cinacalcet were evaluated in children with chronic kidney disease (CKD) and SHPT receiving dialysis. Twelve subjects received a single dose of cinacalcet (0.25 mg/kg) orally or by nasogastric or gastric tube. Subjects were randomized to one of two parathyroid hormone (PTH) and serum calcium sampling sequences: [(1) 2, 8, 48 h; or (2) …

Breaking The Paradigm: Dr Insight Empowers Signature-Free, Enhanced Drug Repurposing, Jinyan Chan, Xuan Wang, Jacob A. Turner, Nicole E. Baldwin, Jinghua Gu

Faculty Publications

Motivation: Transcriptome-based computational drug repurposing has attracted considerable interest by bringing about faster and more cost-effective drug discovery. Nevertheless, key limitations of the current drug connectivity-mapping paradigm have been long overlooked, including the lack of effective means to determine optimal query gene signatures. Results: The novel approach Dr Insight implements a frame-breaking statistical model for the ‘hand-shake’ between disease and drug data. The genome-wide screening of concordantly expressed genes (CEGs) eliminates the need for subjective selection of query signatures, added to eliciting better proxy for potential disease-specific drug targets. Extensive comparisons on simulated and real cancer datasets have validated the …

Discovery Of Selective Probes Targeting Rna Polymerase I, Xiao Tan

Theses and Dissertations--Chemistry

RNR Polymerase I (RNA Pol I) is a “factory” that orchestrate the transcription of ribosomal rRNA for constructing ribosomes as a primary workshop for protein translation to sustain cell growth. Misregulation of RNA Pol I can cause uncontrolled cell proliferation, which leads to the development of cancer. Yeast (Saccharomyces cerevisiae) is a valuable model system to study RNA Pol I. Recently, the X-ray crystal structure of the yeast homologue of RNA Pol I was elucidated, offering the structural basis to selectively target this transcriptional machinery. The approach to selective RNA Pol I targeting was to disrupt the interaction …

Identification Of Antibiotic Ge37468a From Pseudonocardia Symbionts Of Trachymyrmex Septentrionalis Ants, Krithika Rao

Scripps Senior Theses

In response to the growing rates of antibiotic resistance in human bacterial pathogens, this study explores the natural products involved in the defensive symbiosis between actinobacteria and fungus-growing ants to uncover new potential antibiotics. This study also seeks to understand the function of natural antibiotics in their ecological contexts, especially those involved in defensive symbioses. Defensive symbiosis can be a beneficial platform for discovering useful antibiotics, because antibiotics in these relationships must be able to selectively inhibit enemies without harming hosts, and are therefore likely more specific and less toxic. Pseudonocardia sp. associated with Trachymyrmex septentrionalis ants demonstrated antibiotic activity …

Development And Ex Vivo Characterization Of Enteric Coated Chitosan Beads For Crohn’S Disease Management, Craig Mendonca

University Scholar Projects

Drug delivery is the process of transporting a drug to its site of action. It includes controlled delivery, where the drug is released at the tissue in a regulated manner. Additionally, it includes targeted delivery, where the drug is aimed at a specific tissue or region to avoid unwanted side effects (that would occur if the drug were distributed throughout the body). A cellulose acetate phthalate coated chitosan bead was developed as a formulation for controlled and targeted release of dexamethasone to the ilium and colon. This formulation was determined to be effective in delaying dexamethasone release until the formulation …

Clinical Pharmacology Of Tisagenlecleucel In B-Cell Acute Lymphoblastic Leukemia., Karen Thudium Mueller, Edward Waldron, Stephan A. Grupp, John E. Levine, Theodore W. Laetsch, Michael A. Pulsipher, Michael W. Boyer, Keith August, Jason Hamilton, Rakesh Awasthi, Andrew M. Stein, Denise Sickert, Abhijit Chakraborty, Bruce L. Levine, Carl H. June, Lori Tomassian, Sweta S. Shah, Mimi Leung, Tetiana Taran, Patricia A. Wood, Shannon L. Maude

Manuscripts, Articles, Book Chapters and Other Papers

PURPOSE: Tisagenlecleucel is an anti-CD19 chimeric antigen receptor (CAR19) T-cell therapy approved for the treatment of children and young adults with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL).

PATIENTS AND METHODS: We evaluated the cellular kinetics of tisagenlecleucel, the effect of patient factors, humoral immunogenicity, and manufacturing attributes on its kinetics, and exposure-response analysis for efficacy, safety and pharmacodynamic endpoints in 79 patients across two studies in pediatric B-ALL (ELIANA and ENSIGN).

RESULTS: Using quantitative polymerase chain reaction to quantify levels of tisagenlecleucel transgene, responders (N = 62) had ≈2-fold higher tisagenlecleucel expansion in peripheral blood than nonresponders ( …

December 2018, Randy Curry, Cindy Brooks

RURAL ROCKS

Rural Rocks, the Rural Health Network newsletter by the SWOSU College of Pharmacy

September/October/November 2018, Randy Curry, Cindy Brooks

RURAL ROCKS

Rural Rocks, the Rural Health Network newsletter by the SWOSU College of Pharmacy

Improving The Palatability Of Colonoscopy Preparations, Phuong Anh Hoang Nguyen, Darnell Leon Cuylear, Heather Elizabeth Canavan

Shared Knowledge Conference

Colorectal cancer (CRC) is the second leading cause of cancer-related deaths in the United States. The most reliable screening method of CRC is a colonoscopy which requires a 4-Liter polymer with electrolytes preparation. Two in five patients are non-compliant to their colonoscopy schedules, with many patients who abstain reporting refusal due to significant discomfort associated with this preparation. Furthermore, there are distinct gender differences in the tolerance of colonoscopy preparations in male and female populations. We hypothesize the differences in clinic are a result of toxic effects of the drug associated with poor mixing by individual patients. PEG, the drug, …

Duet: A Phase 2 Study Evaluating The Efficacy And Safety Of Sparsentan In Patients With Fsgs., Howard Trachtman, Peter Nelson, Sharon Adler, Kirk N. Campbell, Abanti Chaudhuri, Vimal Kumar Derebail, Giovanni Gambaro, Loreto Gesualdo, Debbie S. Gipson, Jonathan Hogan, Kenneth Lieberman, Brad Marder, Kevin Edward Meyers, Esmat Mustafa, Jai Radhakrishnan, Tarak Srivastava, Miganush Stepanians, Vladimír Tesar, Olga Zhdanova, Radko Komers, Duet Study Group

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: We evaluated and compared the effects of sparsentan, a dual endothelin type A (ETA) and angiotensin II type 1 receptor antagonist, with those of the angiotensin II type 1 receptor antagonist irbesartan in patients with primary FSGS.

METHODS: In this phase 2, randomized, double-blind, active-control Efficacy and Safety of Sparsentan (RE-021), a Dual Endothelin Receptor and Angiotensin Receptor Blocker, in Patients with Focal Segmental Glomerulosclerosis (FSGS): A Randomized, Double-blind, Active-Control, Dose-Escalation Study (DUET), patients aged 8-75 years with biopsy-proven FSGS, eGFR>30 ml/min per 1.73 m2, and urinary protein-to-creatinine ratio (UP/C) ≥1.0 g/g received sparsentan (200, 400, or 800 …

Azithromycin For Early Pseudomonas Infection In Cystic Fibrosis. The Optimize Randomized Trial., Nicole Mayer-Hamblett, George Retsch-Bogart, Margaret Kloster, Frank Accurso, Margaret Rosenfeld, Gary Albers, Philip Black, Perry Brown, Annemarie Cairns, Stephanie D. Davis, Gavin R. Graff, Gwendolyn S. Kerby, David Orenstein, Rachael Buckingham, Bonnie W. Ramsey, Optimize Study Group

Manuscripts, Articles, Book Chapters and Other Papers

RATIONALE: New isolation of Pseudomonas aeruginosa (Pa) is generally treated with inhaled antipseudomonal antibiotics such as tobramycin inhalation solution (TIS). A therapeutic approach that complements traditional antimicrobial therapy by reducing the risk of pulmonary exacerbation and inflammation may ultimately prolong the time to Pa recurrence.

OBJECTIVES: To test the hypothesis that the addition of azithromycin to TIS in children with cystic fibrosis and early Pa decreases the risk of pulmonary exacerbation and prolongs the time to Pa recurrence.

METHODS: The OPTIMIZE (Optimizing Treatment for Early Pseudomonas aeruginosa Infection in Cystic Fibrosis) trial was a multicenter, double-blind, randomized, placebo-controlled, 18-month trial …

Glimepiride Administered In Chow Reversibly Impairs Glucose Tolerance In Mice, Dana M. Niedowicz, Sabire Özcan, Peter T. Nelson

Sanders-Brown Center on Aging Faculty Publications

Sulfonylureas are a class of antidiabetes medications prescribed to millions of individuals worldwide. Rodents have been used extensively to study sulfonylureas in the laboratory. Here, we report the results of studies treating mice with a sulfonylurea (glimepiride) in order to understand how the drug affects glucose homeostasis and tolerance. We tested the effect of glimepiride on fasting blood glucose, glucose tolerance, and insulin secretion, using glimepiride sourced from a local pharmacy. We also examined the effect on glucagon, gluconeogenesis, and insulin sensitivity. Unexpectedly, glimepiride exposure in mice was associated with fasting hyperglycemia, glucose intolerance, and decreased insulin. There was no …

Oxcarbazepine Overdose In A Polysubstance Related Suicide, Melissa Beals, Robert J. Krumsick, C. Clinton Frazee Iii, Lindsey J. Haldiman, Uttam Garg

Posters

Introduction
Oxcarbazepine is a derivative of carbamazepine that is used primarily in the treatment of epilepsy, and experimentally as a mood-stabilizer in adjunctive therapy for the treatment of bipolar disorder. Oxcarbazepine is converted through oxidation to its pharmacologically active metabolite 10-OH-Carbazepine, which is thought to be responsible for most of the anticonvulsant action of the drug. Adverse effects of oxcarbazepine are generally dose-dependent and may include fatigue, somnolence, dizziness, diplopia, nystagmus, and ataxia. Additive sedative effects have been noted when oxcarbazepine is used in combination with other CNS depressionproducing medications. Furthermore, oxcarbazepine and 10-OH-Carbazepine are powerful CYP2C19 inhibitors, potentially increasing …

Improving The Management Of Nationwide Drug And Iv Bag Shortages, Stephen Tyzik, Mark Parker, Suneela Nayak, Ruth Hanselman, Amy Sparks

Operations Transformation

IMPROVING THE MANAGEMENT OF NATIONWIDE DRUG AND IV SHORTAGE

In September of 2017, Hurricane Maria struck the island of Puerto Rico where over 50 pharmaceutical factories had previously operated. The impact of this was felt not only in the drastic reduction of products that are produced on the island, but it also exacerbated the supply chain issues for key drugs nationwide.

The pharmacy department and supply chain in an academic tertiary care medical center did not have a consistent and reliable process for communication, planning and real-time updates. This resulted in a tremendous amount of wasted staff time at their …

Brain Endothelial Erythrophagocytosis And Hemoglobin Transmigration Across Brain Endothelium: Implications For Pathogenesis Of Cerebral Microbleeds, Rudy Chang, Juan Castillo, Alexander C. Zambon, Tatiana B. Krasieva, Mark J. Fisher, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Peripheral endothelial cells are capable of erythrophagocytosis, but data on brain endothelial erythrophagocytosis are limited. We studied the relationship between brain endothelial erythrophagocytosis and cerebral microhemorrhage, the pathological substrate of MRI-demonstrable cerebral microbleeds. To demonstrate the erythrophagocytic capability of the brain endothelium, we studied the interactions between brain endothelial cells and red blood cells exposed to oxidative stress in vitro, and developed a new in vitro cerebral microbleeds model to study the subsequent passage of hemoglobin across the brain endothelial monolayer. Using multiple approaches, our results show marked brain endothelial erythrophagocytosis of red blood cells exposed to oxidative stress compared …

Interfering With Dna Decondensation As A Strategy Against Mycobacteria, Enzo M. Scutigliani, Edwin R. Scholl, Anita E. Grootemaat, Sadhana Khanal, Jakub A. Kochan, Przemek M. Krawczyk, Eric A. Reits, Atefeh Garzan, Huy X. Ngo, Keith D. Green, Sylvie Garneau-Tsodikova, Jan M. Ruijter, Henk A. Van Veen, Nicole N. Van Der Wel

Pharmaceutical Sciences Faculty Publications

Tuberculosis is once again a major global threat, leading to more than 1 million deaths each year. Treatment options for tuberculosis patients are limited, expensive and characterized by severe side effects, especially in the case of multidrug-resistant forms. Uncovering novel vulnerabilities of the pathogen is crucial to generate new therapeutic strategies. Using high resolution microscopy techniques, we discovered one such vulnerability of Mycobacterium tuberculosis. We demonstrate that the DNA of M. tuberculosis can condense under stressful conditions such as starvation and antibiotic treatment. The DNA condensation is reversible and specific for viable bacteria. Based on these observations, we hypothesized …

Leveraging Pharma To Lower Premiums: Medical Loss Ratio Regulation In The Pharmaceutical Industry, Cami R. Schiel

BYU Law Review

Many recognize escalating drug prices as a significant dilemma related to America’s rising healthcare costs. Yet few can agree on what to do about them. Unaffordable drug prices are a result of many complex forces. One theory to address this problem is to reduce all government intervention and let normal market forces act as they usually do to bring the goods’ prices down to consumer-friendly ranges. However, the prescription drug market is not, and perhaps never can be, a normal market. Reasons for this include (1) a lack of price transparency, (2) information and control asymmetries between patients and physicians, …

Recombinant Human Proteoglycan-4 Reduces Phagocytosis Of Urate Crystals And Downstream Nuclear Factor Kappa B And Inflammasome Activation And Production Of Cytokines And Chemokines In Human And Murine Macrophages, Marwa Qadri, Gregory D. Jay, Ling X. Zhang, Wendy Wong, Anthony M. Reginato, Changqi Sun, Tannin A. Schmidt

Pharmacy Faculty Articles and Research

Microbial biofilms are organized communities of cells that are associated with a wide spectrum of resistant and chronic infections that lead to the treatment failure. Accordingly, there is an urgent demand to create novel effective therapeutic drugs that can inhibit biofilm formation with new mechanisms of action to surmount the current escalating resistance. In this study, in silico hybrid model was utilized to develop three novel short linear peptides (4, 5, and 6) with potential biofilm inhibiting activities (scores > 1.0). The peptides were composed of cationic and hydrophobic residues. They were synthesized using solid-phase strategy. Synthesized peptides were purified and …

August 2018, Randy Curry, Cindy Brooks

RURAL ROCKS

Rural Rocks, the Rural Health Network newsletter by the SWOSU College of Pharmacy

Macromolecule Loading On Plga Particles Through Surface Adsorption, Yiwei Wang

Electronic Theses and Dissertations

The advent of biotherapeutics have impacted the ways in which diseases are treated. In many instances development of recombinant proteins and oligonucleotides into therapeutics are slowed by poor stability of the candidate drugs. Progress has been made in using polymeric particles as carriers of macromolecule drugs. Historically the method is to encapsulate biological drugs into spherical polymeric matrices. Owing to its biocompatible and biodegradable nature, poly (d,l-lactic-co-glycolic acid) (PLGA) has been used extensively in formulating biological drugs into nano- and micro-sized particles. The development of PLGA biologic formulations, however, has been hampered by matrix acidification; the hydrolysis of the polymer …