Medicine and Health Sciences Commons^™

Feasibility Of Aquasolvetm Hpmc-As Lg Via Hot-Melt Extrusion: Effect Of Pressurized Co2 On Physico-Mechanical Properties, Mashan Almutairi

Electronic Theses and Dissertations

The objective of the current study was to investigate the processability of Aquasolve™ HPMC-AS LG via hot-melt extrusion, and to examine the effect of pressurized carbon dioxide (P-CO2) on the physico-mechanical properties of Efavirenz (EFA)-loaded extrudates (EXT). EFA is as a poorly water-soluble drug and HPMC-AS LG was chosen as a carrier for this study. To optimize the process parameters and formulations, various physical mixtures were prepared with the following composition: EFA (30-40-50% w/w) and HPMC-AS LG (70-60-50 % w/w) respectively. Physical mixtures were extruded through the co-rotating twin-screw extruder (16mm Prism Euro Lab, Thermo Fisher Scientific) utilizing a standard …

Strategies For Compliance With Government Regulations In A Pharmaceutical Company, Charles Jagun

Walden Dissertations and Doctoral Studies

Pharmaceutical companies accrued fines of over $30 billion within 25 years because of noncompliance with regulations. Noncompliance with regulations results in fines and an adverse impact on company profitability. Some pharmaceutical company managers lack effective strategies to ensure overall company compliance with regulation. Based on complexity leadership theory, the purpose of this single case study was to explore strategies pharmaceutical company managers used to ensure compliance with regulatory requirements in Nigeria. The target population was functional managers purposely selected because they had successfully implemented strategies for compliance with the regulatory requirements in Nigeria. Data were collected through face-to-face and telephone …

Under-Reporting Of Adverse Drug Reactions To The Food & Drug Administration, James Alexander Lamb

Walden Dissertations and Doctoral Studies

This study examined the potential significant differences in the distribution of adverse drug reactions (ADRs) by reporter (consumer versus physician) and patient outcome at case and event level. This study also contains exploratory questions to evaluate reporting of ADRs by consumers versus physician by system organ class (SOC) and reporter demographics within the United States Food & Drug Administration Adverse Event Reporting System (FAERS). The theoretical foundation applied in this quantitative study was the social amplification of risk framework. Data from the second quarter of 2016 were obtained from FAERS, and a total of 87,807 ADR reports corresponding to 143,399 …

เภสัชจลนศาสตร์ประชากรของยาแวนโคมัยซินในผู้ป่วยเด็กชาวไทย, ชนิกา ชูพันธ์

Chulalongkorn University Theses and Dissertations (Chula ETD)

การศึกษาแบบเก็บข้อมูลย้อนหลังนี้มีวัตถุประสงค์เพื่อสร้างแบบจำลองทางเภสัชจลนศาสตร์และหาปัจจัยที่มีผลต่อค่าพารามิเตอร์ทางเภสัชจลนศาสตร์ของยาแวนโคมัยซินในผู้ป่วยเด็กชาวไทย ค่าความเข้มข้นของ ยาแวนโคมัยซินในซีรั่มจานวน 348 ตัวอย่าง จากผู้ป่วยเด็กอายุระหว่าง 1 เดือน ถึง 18 ปี ที่เข้ารับการรักษา ณ โรงพยาบาลจุฬาลงกรณ์ สภากาชาดไทย ระหว่างปี พ.ศ. 2555-2560 จานวน 212 คน วิเคราะห์ข้อมูลเภสัช จลนศาสตร์ประชากรด้วยโปรแกรม NONMEM® โดยวิธี first-order conditional estimation with interaction ลักษณะทางเภสัชศาสตร์ของยาแวนโคมัยซินอธิบายได้ด้วยแบบจำลองชนิดหนึ่งห้องที่มีการกำจัดยา แบบปฏิกิริยาอันดับหนึ่ง ค่าเฉลี่ยอัตราการกำจัดยาแวนโคมัยซิน (CL) มีค่า 0.13 ลิตร/ชั่วโมง/กิโลกรัม และ ค่าเฉลี่ยปริมาตรการกระจายยา (Vd) มีค่า 0.88 ลิตร/กิโลกรัม ปัจจัยที่มีผลต่อค่าพารามิเตอร์ทางเภสัชศาสตร์ ได้แก่ น้ำหนัก (กิโลกรัม) และอัตราการกรองของไต (มิลลิลิตร/นาที/1.73 ตารางเมตร) ดังแสดงในสมการ CL (ลิตร/ชั่วโมง) = 1.66*(น้ำหนัก/14)[superscript 0.75]*(อัตราการกรองของไต/108.9) และ V (ลิตร) = 12.7*(น้ำหนัก/14) ค่า ความผันแปรระหว่างบุคคลของ CL เท่ากับร้อยละ 34.8 ค่าความผันแปรระหว่างบุคคลของ V เท่ากับร้อยละ 39.6 และแบบจำลองสุดท้ายถูกตรวจสอบความสมเหตุสมผลด้วยวิธี bootstrap และ visual predictive check (VPC) ค่าพารามิเตอร์จากแบบจำลองสุดท้ายมีค่าใกล้เคียงกับค่าพารามิเตอร์ที่ได้จากการทำ bootstrap 1,000 ครั้ง และอยู่ในช่วงความเชื่อมั่นที่ร้อยละ 95 ผลการจำลองข้อมูลด้วยวิธี VPC 1,000 ครั้ง พบค่าความเข้มข้นของ ยาแวนโคมัยซินร้อยละ 6 ที่อยู่นอกช่วงความเชื่อมั่นที่ร้อยละ 90 แสดงถึงความเหมาะสมของแบบจำลองดังกล่าว ในการอธิบายเภสัชจลนศาสตร์ของยาแวนโคมัยซิน

Scalable Feature Selection And Extraction With Applications In Kinase Polypharmacology, Derek Jones

Theses and Dissertations--Computer Science

In order to reduce the time associated with and the costs of drug discovery, machine learning is being used to automate much of the work in this process. However the size and complex nature of molecular data makes the application of machine learning especially challenging. Much work must go into the process of engineering features that are then used to train machine learning models, costing considerable amounts of time and requiring the knowledge of domain experts to be most effective. The purpose of this work is to demonstrate data driven approaches to perform the feature selection and extraction steps in …

Alpha-Glucosidase Inhibitors From Dendrobium Scabrilingue, Chalermporn Sarakulwattana

Chulalongkorn University Theses and Dissertations (Chula ETD)

Phytochemical study of the methanol extract of the whole plant of Dendrobium scabrilingue Lindl. (Orchidaceae) resulted in the isolation of a new phenanthrene and a new bisbibenzyl namely dendroscabrols A and B, respectively, along with eight known compounds, identified as (Z)-ferulic acid tetracosyl ester, (E)-ferulic acid tetracosyl ester, gigantol, batatasin III, coelonin, aloifol I, lusianthridin and RF-3192C. The structures of these isolated compounds were determined mainly by spectroscopic data. All isolates were examined for alpha-glucosidase inhibitory activity. Dendroscabrol B and RF-3192C exhibited the most potent activity. In addition, dendroscabrol A, gigantol, coelonin and lusianthridin displayed strong activity compared with the …

Novel Regulatory Mechanisms Of Protein Kinase B On Apoptosis Susceptibility And Cancer Dedifferentiation, Arnatchai Maiuthed

Chulalongkorn University Theses and Dissertations (Chula ETD)

No abstract provided.

A Comprehensive Examination Of The Pharmacist's Role In Mental Illness, Kaleb D. Barnes

Honors Theses

The number of people receiving mental illness diagnoses has increased in the last two decades. As one of the most accessible healthcare professionals, pharmacists need to be prepared to assist in the management of patients with mental illness. In this study, the objective was to see how pharmacists' mental illness knowledge, acceptable social distance, familiarity, and perceived barriers may predict pharmacists' attitude toward patients with mental illness and also their willingness to provide care to patients with mental illness. The secondary objectives of this study were to test for differences in knowledge, attitude, perceived barriers, and willingness to provide care …

An Evaluation Of Mobile Apps For The Collation Of Materials To Propose An App For Type-2 Diabetes Self-Management, Sydney Watson

Honors Theses

This study is an evaluation of mobile application (apps) with the intention to collate materials appropriate for the proposal of a mobile app for type 2 diabetes self-management. In order to decipher the most vital aspects to be included in the app, an evaluation of mobile apps pertaining to nutrition and diabetes management were investigated. It was found that there is a lack of mobile apps that have all-encompassing features regarding the management of the disease. Future app developers looking to develop a mobile app that is efficient in type 2 diabetes self-management should include each feature as follows: blood …

Dysregulation Of Human Phase I Enzymes In Apap Overdose Subjects With Low Alt Levels, Aaron Woodall

Honors Theses

Background: Acetaminophen (APAP) is a common analgesic that can cause liver injury and death in high doses. Changes in gene expression following APAP overdose may be more sensitive indicators of liver injury than the current clinical indicator, alanine aminotransferase (ALT). The aim of this study was to examine gene expression of Phase I enzymes in pediatric APAP overdose patients with low ALT levels (<75 lU/L), in order to understand the mechanism of APAP toxicity.

Methods: Blood samples were collected from control patients (no APAP exposure; N=5) and APAP overdose patients (N=S). Using the PAXgene system, RNA was extracted from the blood samples and cDNA was synthesized. Quantitative polymerase chain reaction …

The Development Of Novel Non-Peptide Proteasome Inhibitors For The Treatment Of Solid Tumors, Zachary C. Miller

Theses and Dissertations--Pharmacy

The proteasome is a large protein complex which is responsible for the majority of protein degradation in eukaryotes. Following FDA approval of the first proteasome inhibitor bortezomib for the treatment of multiple myeloma (MM) in 2003, there has been an increasing awareness of the significant therapeutic potential of proteasome inhibitors in the treatment of cancer. As of 2017, three proteasome inhibitors are approved for the treatment of MM but in clinical trials with patients bearing solid tumors these existing proteasome inhibitors have demonstrated poor results. Notably, all three FDA-approved proteasome inhibitors rely on the combination a peptide backbone and reactive …

Predictors Of Dental Opioid Analgesic Prescribing, Opioid Use And Dental Emergency Department Visits In The Mississippi Medicaid Population, Chukwuebuka Dibie

Electronic Theses and Dissertations

OBJECTIVES: The objectives of this study were: (1) to determine prevalence of opioid analgesics prescribing for non-ED dental related visits in the Mississippi Medicaid population, (2) to assess predictors of receiving opioid analgesics following non-ED dental related events among Mississippi Medicaid beneficiaries, and (3) to determine prevalence of opioid analgesic prescribing for dental related emergency departments (ED) visits in the Mississippi Medicaid population. METHODS: A retrospective, cross-sectional, observational database analysis using Mississippi Medicaid administrative claims data from January 1, 2015 to December 31, 2016. Beneficiaries with dental related visits were included in this study. Descriptive statistics were utilized to assess …

Novel Applications Of Hot-Melt Extrusion Technology, Ajinkya Moreshwar Bhagurkar

Electronic Theses and Dissertations

Hot-melt extrusion, an adaptable technology, has established its position in a wide spectrum of manufacturing operations like amorphous solid dispersions, immediate and controlled oral formulations, implants, and taste masked products. In recent years the industrial focus has shifted towards continuous manufacturing, thus melt extrusion is being explored for new applications. The aim of this research work was to investigate the novel applications of hot-melt extrusion by carrying out an in depth study to understand the interplay between the process and the product. The conventional techniques used for the preparation of ointments and nanostructured lipid carriers are multi-step and time consuming …

A Multifactorial Cytochrome P450 2d6 Genotype-Phenotype Prediction Model To Improve Precision Of Clinical Pharmacogenomic Tests, Rachel Dalton

Graduate Student Theses, Dissertations, & Professional Papers

BACKGROUND: CYP2D6 is difficult to accurately genotype due to a large number of single nucleotide variants (SNVs), indels, and structural variation such as deletions, duplications, and CYP2D6/CYP2D7 hybrid genes. CYP2D6 targeted genotyping panels are of limited utility; clinically relevant variants that are not genotyped will be missed. Sequencing solves this problem but requires additional tools to address structural variation. The goal of our study was to determine the predictive power of Stargazer, a novel allele-calling program, which combines SNV/indel calls with structural variation identification.

METHODS: In a panel of 309 human livers, CYP2D6 diplotypes and activity scores were initially assigned …

Mechanisms Of Rad51d-Dependent Repair Of Dna And Telomere Damage Induced By Interstrand Crosslinking Agents And Thiopurines, Nicole M. Reilly

Theses and Dissertations

Mutations in homologous recombination (HR) genes increase genomic instability, an enabling characteristic of cancer. However, the status of these same genes can also determine chemotherapy outcomes. RAD51D is a breast and ovarian cancer susceptibility gene that is an important component of HR. Mammalian cells defective for RAD51D have extensive chromosomal aberrations and are more sensitive to the interstrand crosslink-inducing agent mitomycin C (MMC) and the thiopurine 6-thioguanine (6TG). Previously, the RNF138 E3 ubiquitin ligase was identified to promote RAD51D ubiquitination, and loss of RNF138 also increased cellular sensitivity to MMC. Ubiquitination assays were used to show that a 3-ubiquitin modification …

Kv7 Channels Of The Urinary Bladder Smooth Muscle: Functional Roles And Therapeutic Potential, Aaron Provence

Theses and Dissertations

Overactive bladder (OAB) is a pervasive and debilitating condition for which effective therapeutic modalities are lacking. As potential novel pharmacological targets for lower urinary tract dysfunction, our recent studies have demonstrated voltage-gated KV7 channels (KV7.1-KV7.5) to be functionally expressed in detrusor smooth muscle (DSM) of the urinary bladder. Nonetheless, the specific roles of individual KV7 channel subtypes remains poorly understood. Using Western blot, immunocytochemistry, isometric DSM tension recordings, ratiometric fluorescence Ca2+ imaging, and patch-clamp electrophysiology, we demonstrated expression and key physiologic roles for the KV7.2/KV7.3 channels in guinea pig DSM using the novel and selective KV7.2/KV7.3 channel opener N-(2-Chloro-5-pyrimidinyl)-3,4-difluorobenzamide (ICA-069673). …

Evaluation Of Anthelmintic Properties And Toxicity Of Pure Compounds Isolated From Dalea Spp (Plantae, Fabaceae), Victoria Lh Mcpherson

All Master's Theses

Infecting upwards of a billion people worldwide, hookworm is one of the most prevalent parasitic infections affecting the world today. Those infected experience hookworm disease, characterized by severe anemia, which can lead to malnutrition, low birth weights, and physical and mental impairments. Currently, the benzimidazoles albendazole and mebendazole are used as the primary treatment; however, resistance to these drugs is emerging. Due to this resistance, finding new anthelmintic compounds active against hookworm is a priority. Previously, a pure compound isolated from Dalea ornata was identified as having strong anthelmintic activity when used against the hookworm Ancylostoma ceylanicum. This project …

Investigations On Cancer Cell Biological Effects Of Cdk8 Inhibitor Q-12, Zhixin Lu

University of the Pacific Theses and Dissertations

Over the past two decades, protein kinases have been intensively investigated as targets to treat neoplastic diseases. Many protein kinase inhibitors not only have therapeutic potential but are becoming invaluable reagents for the study of cell signaling.

We aspired to use our Cyclin-Dependent Kinase 8 inhibitor, Q-12, as a probe for biomarker discovery for CDK8 inhibitor sensitive tumor types. Q-12 shows potent inhibition of cell viability and induction of apoptosis process in some triple-negative breast cancer and colorectal cancer cell lines in vitro. Western blot results indicate that the reduction of STAT1 phosphorylation could be a robust indicator of CDK8 …

Bimetallic Complexes: The Fundamental Aspects Of Metal-Metal Interactions, Ligand Sterics And Application, Michael Bernard Pastor

University of the Pacific Theses and Dissertations

Metal containing complexes have been used to catalyze various organic transformations for the past few decades. The success of several mononuclear catalysts led to transition metal catalysts used in pharmaceuticals, environmental, and industrial processes. While mononuclear complexes have been used extensively, bimetallic systems have received far less attention. Bimetallic or polynuclear sites are commonly found in metalloenzymes that perform elegant transformation in biological systems, underlying their significance. Inorganic chemists take inspiration from nature and design model bimetallic complexes to further study this cooperativity effect. A bimetallic platform offers many structural and functional differences such as the identity of the metal …

Peptide-Drug Conjugate For Her2-Targeted Drug Delivery, Yan Wang

University of the Pacific Theses and Dissertations

Recent strategies for anticancer drug design have been focused on utilizing antibody as a drug or targeted moiety for targeted drug delivery. Antibody−drug conjugates (ADCs) have become a promising new class of targeted therapeutic agents for treatment of cancer. ADCs are designed to preferentially direct a cytotoxic drug to a cell-surface antigen recognized by an antibody. However, there are some challenges in developing ADCs, such as limited solid tumor penetration, high manufacturing costs and antibody-drug stoichiometry. Smaller molecules such as peptides have been shown to specifically bind to cancer related targets. These peptides can be used to form peptide-drug conjugates …

Determining The Role Played By Aryl Hydrocarbon Receptor (Ahr) In The Colon Carcinoma Tumor Model, Poonam Yakkundi

University of the Pacific Theses and Dissertations

Aryl hydrocarbon receptor (AHR), commonly known as an environmental sensor involved in the metabolism and elimination of xenobiotic substances, is also an important modulator in the development and functioning of the immune system. AHR expression is varied in the T cell subsets with the highest expression in T-helper 17 and T regulatory cells. Work from many researchers has suggested that AHR can act as a tumor promoter or a tumor suppressor depending on the tumor type. Our goal is to understand the role played by AHR in MC38 syngeneic colon carcinoma tumor model. In the absence of AHR, MC38 tumor …

The Effects Of Stand-Alone Prescription Drug Plans On Health Care Utilizations, Expenditures And Medication Adherence Among Elderly Medicare Beneficiaries, Jing Yuan

Theses and Dissertations

Since the implementation of Medicare Part D in 2006, a growing body of evidence has shown that Medicare Part D might offset the total healthcare spending by improving the use of prescription drugs. However, little is known about the impact of different types of Part D plans – Stand-alone Prescription Drug Plan (PDPs) and Medicare Advantage Prescription Drug Plan (MA-PDs) – on health care utilizations and expenditures. This dissertation examined the association between the effect in PDPs on health care utilizations as well as expenditures, and medication adherence among elderly Medicare beneficiaries, compared to MA-PDs. Data was pooled from 2006-2010 …