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Modulation Of Diet-Induced Gut Inflammation In Slowing Initiation Of Hematologic Malignancies, Esther Nyarkoa Mensah Jan 2024

Modulation Of Diet-Induced Gut Inflammation In Slowing Initiation Of Hematologic Malignancies, Esther Nyarkoa Mensah

Theses, Dissertations and Capstones

The intestinal tract serves as a host to an extremely complex microbial system. Microbes in the gut regulate their metabolism in response to chemicals generated by other microorganisms as well as nutrition supply from dietary intake. Alterations in gut bacteria have been implicated in the development of metabolic disorders such as obesity and the progression of diseases such as Myelodysplastic syndromes (MDS). Although the cause of obesity is multifactorial, the consumption of high-fat or sugar-rich diets (Western diets) has been proposed as a significant contributor to this global epidemic. Obesity is a major public health concern that has been extensively …


Increasing The Efficacy Of Actinomycin D With Resveratrol In Aerodigestive Tract Cancers, Lukmon Morenikeji Raji Jan 2024

Increasing The Efficacy Of Actinomycin D With Resveratrol In Aerodigestive Tract Cancers, Lukmon Morenikeji Raji

Theses, Dissertations and Capstones

Chemotherapy poses a significant challenge for cancer patients due to drug-associated toxicity, which often results from their effects on both healthy (normal) and cancerous cells. While various options aim to reduce toxicity and optimize beneficial effects, a comprehensive solution remains elusive. Cyclotherapy is one such approach developed to protect normal cells from the toxic effects of chemotherapy drugs. The basic principle underlying cyclotherapy is p53- dependent cell cycle arrest of normal cells while killing cancer cells via a p53-independent mechanism using a second drug. In our research, we investigated the inhibitory effects of a combination of two low-dose anticancer drugs, …


Artificial Intelligence Is Revolutionizing Controlled Substance Diversion Detection, Brian Cox, Alberto Coustasse, Craig Kimble Sep 2023

Artificial Intelligence Is Revolutionizing Controlled Substance Diversion Detection, Brian Cox, Alberto Coustasse, Craig Kimble

Management Faculty Research

In community and institutional health care sectors, artificial intelligence (AI) use is expanding. AI is being tapped broadly in operations, customer service, and scheduling, with major pharmacy chains such as Kroger, CVS, and Walgreens, already starting to implement AI applications in their pharmacies. So far, Kroger has begun to use AI for employee onboarding and training processes, CVS is applying AI in negotiations with suppliers, and Walgreens is using it to streamline vaccine scheduling. With these advances in major pharmacy chains, the next extensive application for AI has become clearer: diversion monitoring. Diversion occurs in health care settings when a …


Navigating The Path To Safe Compounding In Health Systems, Thomas Pile, Craig Kimble, Alberto Coustasse Jul 2023

Navigating The Path To Safe Compounding In Health Systems, Thomas Pile, Craig Kimble, Alberto Coustasse

Management Faculty Research

Across the country health systems are facing increasing drug shortages that are forcing pharmacists to rely far more heavily on compounding to meet the needs of patients. Additionally, several high-profile compounding incidents have helped highlight the importance of ensuring best practices are followed during sterile and nonsterile compounding to support patient safety and high-quality care. Specifically, in 2022, 160 drug shortages were reported in pharmacies. From January 1, 2023, to March 31, 2023, 47 drug shortages were reported, 55% of which were for injectables. In response, compounding has increasingly become a solution to bridge that gap.


Eruptive Lentigines Confined To Resolving Psoriatic Plaques Following Treatment With Guselkumab, Jacob R. Kilgore Md, James C. Curry, Shane E. Cook Md Apr 2023

Eruptive Lentigines Confined To Resolving Psoriatic Plaques Following Treatment With Guselkumab, Jacob R. Kilgore Md, James C. Curry, Shane E. Cook Md

Marshall Journal of Medicine

Eruptive lentigines in the area of resolving psoriatic plaques has been well documented in the literature following successful treatment with multiple therapies. This is historically associated with light treatment but has been expanded to include other therapies such as anti-tumor necrosis factor therapies and, more recently, some biologics5. Guselkumab (Tremfya) is an IgG1λ monoclonal antibody used in the treatment of plaque psoriasis with only one case of eruptive lentigines confined to resolving psoriatic plaques (ELRP) noted as a side effect. We present the second such case of ELRP associated with successful treatment of plaque psoriasis with Guselkumab, as …


Closed-System Transfer Devices Reduce Exposure To Contaminants, Ken Maxik, Craig Kimble, Alberto Coustasse Mar 2023

Closed-System Transfer Devices Reduce Exposure To Contaminants, Ken Maxik, Craig Kimble, Alberto Coustasse

Management Faculty Research

Closed-system transfer devices (CSTDs) are used during the preparation of hazardous drugs (HDs) as a mechanism to reduce the transfer of drugs or vapors into the environment. When evaluating these systems, pharmacists should consider which drugs in the pharmacy would benefit the safety of health care workers and patients using the systems. Medication types include neoplastic agents, such as bleomycin, cisplatin, and methotrexate, and other agents, such as cyclosporine, oxytocin, and progesterone.


Effects Of Disulfiram On The Metabolome Of Mrsa, Surya Teja Naidu Jan 2023

Effects Of Disulfiram On The Metabolome Of Mrsa, Surya Teja Naidu

Theses, Dissertations and Capstones

Disulfiram, known as Antabuse®, is an oral drug for the treatment of alcohol dependence. Previous studies have indicated that disulfiram (DSF) exhibits antibacterial effects, particularly against Gram-positive bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA). Our study delves into the antibacterial mechanism of DSF in MRSA through High-Pressure Liquid Chromatography (HPLC) metabolomics, investigating the underlying mechanism of DSF effects on thiamine and amino acid metabolism. Thiamine pyrophosphate (TPP) plays a crucial role as a cofactor for critical enzymes such as transketolase, pyruvate dehydrogenase, and 2-oxoglutarate dehydrogenase. These enzymes are integral to the carbohydrate metabolism process within bacterial cells. TPP also contributes …


Elucidating The Impact Of Western Diet On Bone Marrow Cytokine Signatures: Understanding Poor Outcomes In Susceptibility To Infection And Progression Of Cancer, Lahari Kondeti Jan 2023

Elucidating The Impact Of Western Diet On Bone Marrow Cytokine Signatures: Understanding Poor Outcomes In Susceptibility To Infection And Progression Of Cancer, Lahari Kondeti

Theses, Dissertations and Capstones

Among other disease outcomes, obesity is associated with 1) reduction in long-lasting immune protection and 2) acquisition of cancer. Given our interest in hematopoietic stem and progenitor cell (HSPC) dynamics, we questioned if similar mechanisms in the bone marrow microenvironment contribute to obesity-induced HSPC alterations responsible for 1) decreased immune protection and 2) transformation of HSPCs in the pathogenesis of hematologic malignancies. The negative effects of obesity on immune protection are most notably established in influenza models. Influenza infection susceptibility is increased and influenza vaccine-induced immunity wains in obese individuals. Ongoing studies aim to define mechanisms for waning immunity at …


Pharmacology Of Disulfiram As An Antibacterial Agent, Yogesh Meka Jan 2023

Pharmacology Of Disulfiram As An Antibacterial Agent, Yogesh Meka

Theses, Dissertations and Capstones

Disulfiram (Antabuse®) is an oral prescription drug used to treat alcohol abuse disorder (AUD). Disulfiram (DSF) and its metabolites act on the body by inhibiting multiple enzymes involved in alcohol metabolism. This study aims to understand the pharmacology of disulfiram as an antibacterial medication. Previous studies on DSF showed antibiotic activity against multidrug-resistant Staphylococcus aureus strains (MRSA). The initial aim of this study was to decipher the mechanisms involved in inhibiting bacterial growth by DSF, which was done by performing biochemical studies. The studies revealed that DSF had antagonistic effects on redox buffering and energy production. Another aim of this …


Evaluate 503b Facilities For Outsourced Compounds, Sarah Clemente, Brittany Riley, Alberto Coustasse Nov 2022

Evaluate 503b Facilities For Outsourced Compounds, Sarah Clemente, Brittany Riley, Alberto Coustasse

Pharmacy Practice & Administration

The US health care system has encountered long-standing, complex challenges, including growing costs, overuse of care, staffing shortages and supply chain weaknesses. COVID-19 revived these pressures, transforming the health care landscape. Medication and staffing shortages plague hospital systems, and pharmacies are not exempt. Most health systems have experienced high levels of pharmacy technician turnover, with most reporting a minimum turnover rate of 21% last year. In addition, medication shortages of critical medications and infusions create significant workflow barriers that hospitals must address to ensure patient safety. In the face of these obstacles, health systems are turning to 503B compounding facilities …


Radio Frequency Identification Enhances Patient Safety, Craig Kimble, Alberto Coustasse, Ken Maxik Nov 2022

Radio Frequency Identification Enhances Patient Safety, Craig Kimble, Alberto Coustasse, Ken Maxik

Pharmacy Practice & Administration

Radio Frequency Identification (RFID) is a technology that uses tags and readers to identify and collect asset information. In pharmacies, this usually means RFID is used for high cost equipment or pharmaceuticals. RFID applications have been in use for many years but recently gained traction in health systems. RFID is becoming particularly effective in drug inventory and automation applications, such as medication carousels and pick-to-light systems.


Is The 340b Hospitals Battle At The Supreme Court Over?, Casey W.. Baker, Susan W. Lanham, Alberto Coustasse Nov 2022

Is The 340b Hospitals Battle At The Supreme Court Over?, Casey W.. Baker, Susan W. Lanham, Alberto Coustasse

Accounting Faculty Research

Under the Federal 340B Program, hospitals and eligible health care clinics that serve low income or rural populations can qualify for federally negotiated manufacturer discounts on purchases of prescription drugs. Approximately 50,000 entities participate in the 340B program, where pharmaceutical manufacturers are instructed to supply outpatient medications to participating providers at discounted rates of 20% to 50%. Participating hospitals depend on profits from the differential between their reimbursement for these drugs and the discounted rates they disburse to finance affordable patient care in underserved communities. On June 15, 2022, the US Supreme Court ruled that major cuts to 340B payments …


Gabapentin Presents High Potential For Misuse, Alberto Coustasse, Stacie Deslich, Susan W. Lanham, Brittany Riley Nov 2022

Gabapentin Presents High Potential For Misuse, Alberto Coustasse, Stacie Deslich, Susan W. Lanham, Brittany Riley

Management Faculty Research

The FDA Approved Gabapentin in 1993 as a non-controlled substance and it has remained a non-controlled substance at the federal level. The drug was created as an anticonvulsant and used to treat seizure disorders. The medication has also been used to treat hot flashes, neuropathic pain, pain, postoperative nausea, substance abuse issues, and vomiting. It is estimated that approximately 1% of people in the United States misuse gabapentin. This fact has compelled certain states to generate legislative initiatives designed to monitor the use and/or reclassify gabapentin. In 2019, US pharmacies dispensed 69 million prescriptions for gabapentin.


Prescribing Controlled Substances Goes Electronic, Alberto Coustasse, Craig Kimble, Ken Maxik Sep 2022

Prescribing Controlled Substances Goes Electronic, Alberto Coustasse, Craig Kimble, Ken Maxik

Management Faculty Research

With the Affordable Care Act in 2010 came interoperability and meaningful use requirements. Part of these requirements included the implementation of electronic medical records (EMRs), which was a crucial part of achieving these standards. With EMRs, prescribers began sending electronic prescriptions. EMRs can provide advanced decision support when writing prescriptions, and they include features such as auto populating the quantity prescribed, formulary information, therapeutic duplications, warnings about interactions, or other potential clinical or regulatory issues. This system results in enhanced patient care and a more streamlined dispensing process. In addition, electronic prescriptions for controlled substances (EPCS) has become more widely …


Treatment Of Tardive Dyskinesia With High Dose Vitamin B6 Associated With Depression, Marjorie Mccoy, Adam Schindzielorz, Suzanne Holroyd Jul 2022

Treatment Of Tardive Dyskinesia With High Dose Vitamin B6 Associated With Depression, Marjorie Mccoy, Adam Schindzielorz, Suzanne Holroyd

Marshall Journal of Medicine

Tardive dyskinesia (TD) is a movement disorder associated with dopamine receptor blocking medications. Recommended treatments for TD include discontinuing the causative agent, adding vesicular monoamine transporter 2 (VMAT2) inhibitors, or adding vitamin B6. We present a 66-year-old Caucasian male with bipolar I disorder who developed TD while on lithium and quetiapine having been euthymic on this regimen for three years. He was initially treated with 1200 mg B6 daily. This failed to improve his TD and was associated with a depressive episode. He switched to valbenazine 40 mg daily which improved his TD and concurrently his mood, but months later …


Association Of Electronic Medical Records And Opioid Prescription, Archana Suwal, Jemimah Okonjo, Stacie Deslich, Alberto Coustasse Mar 2022

Association Of Electronic Medical Records And Opioid Prescription, Archana Suwal, Jemimah Okonjo, Stacie Deslich, Alberto Coustasse

Management Faculty Research

A Prescription Drug Monitoring Program (PDMP) is an electronic database that tracks controlled substance prescriptions in a state. PDMPs can provide health authorities timely information about prescribing and patient behaviors that contribute to the epidemic and facilitate an agile and directed response. Electronic Prescribing for Controlled Substances (EPCS) aimed to eliminate paper prescriptions by allowing clinical prescribers to write prescriptions electronically, making them digital and trackable for both the prescriber and the pharmacist and has been an essential part of any health information technology system, as well as a requirement for 'meaningful use' (Blumenthal & Tavenner, 2010). However, one of …


Race And Sex Associations With Tacrolimus Pharmacokinetics In Stable Kidney Transplant Recipients, Kathleen M. Tornatore, Calvin J. Meaney, Kristopher Attwood, Daniel A. Brazeau, Gregory E. Wilding, Joseph D. Consiglio, Aijaz Gundroo, Shrley S. Chang, Vanessa Gray, Louise M. Cooper, Rocco C. Venuto Feb 2022

Race And Sex Associations With Tacrolimus Pharmacokinetics In Stable Kidney Transplant Recipients, Kathleen M. Tornatore, Calvin J. Meaney, Kristopher Attwood, Daniel A. Brazeau, Gregory E. Wilding, Joseph D. Consiglio, Aijaz Gundroo, Shrley S. Chang, Vanessa Gray, Louise M. Cooper, Rocco C. Venuto

Pharmaceutical Science and Research

Study Objective: This study investigated race and sex differences in tacrolimus pharmacokinetics and pharmacodynamics in stable kidney transplant recipients.

Design and Setting: A cross-sectional, open-label, single center, 12-h pharmacokinetic-pharmacodynamic study was conducted. Tacrolimus pharmacokinetic parameters included area under the concentration-time curve (AUC0–12), AUC0–4, 12-h troughs (C12 h), maximum concentrations (Cmax), oral clearance (Cl), with dose-normalized AUC0–12, troughs, and Cmax with standardized adverse effect scores. Statistical models were used to analyze end points with individual covariate-adjustment including clinical factors, genotypic variants CYP3A5*3, CYP3A5*6, CYP3A5*7(CYP3A5*3*6*7 …


Store, Handle, And Administer Vaccines Safely To Prevent Errors, Craig Kimble, Kenneth Maxik, Alberto Coustasse Jan 2022

Store, Handle, And Administer Vaccines Safely To Prevent Errors, Craig Kimble, Kenneth Maxik, Alberto Coustasse

Management Faculty Research

Insufficient training, multiple manufacturers, and noninterchangeable products increase the risk of vaccine-related errors. Increasing the complexity are the addition of boosters with different doses, personnel new to the vaccine administration process, changes in dosing, easily misidentified labeling or products, vaccines given together, and the interchanging of booster products.2,3 As a result, there is an increased need to be alert in safety efforts with vaccine administration and storage. Pharmacy staff members must work together to improve safety and prevent vaccine-related errors.


Prenatal Exposure To Methamphetamine Causes Vascular Dysfunction In Adult Male Offspring, Hasitha Chavva, Adam M. Belcher, Daniel A. Brazeau, Boyd Rorabaugh Jan 2022

Prenatal Exposure To Methamphetamine Causes Vascular Dysfunction In Adult Male Offspring, Hasitha Chavva, Adam M. Belcher, Daniel A. Brazeau, Boyd Rorabaugh

Pharmaceutical Science and Research

Methamphetamine use during pregnancy can have negative consequences on the offspring. However, most studies investigating the impact of prenatal exposure to methamphetamine have focused on behavioral and neurological outcomes. Relatively little is known regarding the impact of prenatal methamphetamine on the adult cardiovascular system. This study investigated the impact of chronic fetal exposure to methamphetamine on vascular function in adult offspring. Pregnant female rats received daily saline or methamphetamine (5 mg/kg) injections starting on gestational day 1 and continuing until the pups were born. Vascular function was assessed in 5 month old offspring. Prenatal methamphetamine significantly decreased both the efficacy …


Help Patients Safely Handle Medications To Improve Adherence, Kenneth Maxik, Craig Kimble, Alberto Coustasse Nov 2021

Help Patients Safely Handle Medications To Improve Adherence, Kenneth Maxik, Craig Kimble, Alberto Coustasse

Management Faculty Research

Medication nonadherence can cause many drug-related adverse effects (AEs), and pharmacists are in a prime position to use every patient interaction as an opportunity to address barriers, improve adherence, and increase the safe management of medications.


Law Helps Ensure Safety Of The Supply Chain, Kenneth Maxik, Craig Kimble, Alberto Coustasse Sep 2021

Law Helps Ensure Safety Of The Supply Chain, Kenneth Maxik, Craig Kimble, Alberto Coustasse

Management Faculty Research

The Drug Quality and Security Act was signed into law on November 27, 2013, and included the Title 2 Drug Supply Chain and Security Act (DSCSA). This legislation was introduced to enact a federal prescription drug safety standard to decrease contamination, counterfeiting, diversion, and otherwise harmful illicit activities. It also improves the detection and elimination of potentially unsafe drugs from the drug supply chain to protect US consumers.


Detect Adverse Events And Medication Errors Using Technology, Kenneth Maxik, Craig Kimble, Alberto Coustasse May 2021

Detect Adverse Events And Medication Errors Using Technology, Kenneth Maxik, Craig Kimble, Alberto Coustasse

Pharmacy Practice & Administration

Technology has changed the practice of pharmacy. Many systems are now part of an ever increasingly interfaced or integrated health care system allowing the electronic exchange of prescriptions from electronic health records (EHRs) to the pharmacy information system and bidirectional data exchange for many items, such as lab results and test information. With meaningful use of automated distribution cabinet databases, EHR efforts, electronic data exchange, and smart pump technology, the availability of data to use for addressing and preventing adverse medication events has grown. Use of these systems has allowed a data-rich environment to store and retrieve reporting. Mining data …


Methamphetamine-Induced Changes In Myocardial Gene Transcription Are Sex-Dependent, Hasitha Chavva, Daniel A. Brazeau, James Denvir, Donald A. Primerano, Jun Fan, Sarah L. Seeley, Boyd R. Rorabaugh Apr 2021

Methamphetamine-Induced Changes In Myocardial Gene Transcription Are Sex-Dependent, Hasitha Chavva, Daniel A. Brazeau, James Denvir, Donald A. Primerano, Jun Fan, Sarah L. Seeley, Boyd R. Rorabaugh

Pharmaceutical Science and Research

Background: Prior work demonstrated that female rats (but not their male littermates) exposed to methamphetamine become hypersensitive to myocardial ischemic injury. Importantly, this sex-dependent effect persists following 30 days of subsequent abstinence from the drug, suggesting that it may be mediated by long term changes in gene expression that are not rapidly reversed following discontinuation of methamphetamine use. The goal of the present study was to determine whether methamphetamine induces sex-dependent changes in myocardial gene expression and whether these changes persist following subsequent abstinence from methamphetamine.

Results: Methamphetamine induced changes in the myocardial transcriptome were significantly greater in female hearts …


Change Management Is A Consideration Beyond The Pandemic, Kenneth Maxik, Craig Kimble, Alberto Coustasse Mar 2021

Change Management Is A Consideration Beyond The Pandemic, Kenneth Maxik, Craig Kimble, Alberto Coustasse

Pharmacy Practice & Administration

Change management (CM) is a well-organized framework for managing the people side of change. It includes practices, processes, and planned activities designed to facilitate and lead organizations to move from the present state to a desired state. The goal of CM is not to eliminate resistance but to anticipate it, proactively plan for it, continuously manage it, and mitigate the consequences.


Drug Delivery Systems: Exploring Rheological Properties And Therapeutic Effect Of 5-Fu Chitosan Gel For Topical Wound Healing, Samuel Tetteh-Quarshie Jan 2021

Drug Delivery Systems: Exploring Rheological Properties And Therapeutic Effect Of 5-Fu Chitosan Gel For Topical Wound Healing, Samuel Tetteh-Quarshie

Theses, Dissertations and Capstones

Diabetic skin wound is a common complication of diabetes that occurs in about 15% of diabetic patients and often requires prolonged hospitalization for its management and treatment. Natural polymers are used for wound dressing due to their biological adhesiveness, non-toxicity, and biodegradable nature. 5-Fluorouracil (FU) has been shown to alter adipokine expression which is implicated in cutaneous wound repair. Thus, our overall objective was to investigate the utility of chitosan (CS) gel for topical delivery of 5-FU to treat diabetic wounds. We prepared chitosan gel (2% w/w) in serial dilutions of 5-FU (25μg/mL, 2.5μg/mL, 0.25μg/mL, and 0.025μg/mL) and evaluated their …


Association Of Electronic Prescription In Controlled Substances Used, Archana Suwal, Jemima Akinyi Okonjo Jan 2021

Association Of Electronic Prescription In Controlled Substances Used, Archana Suwal, Jemima Akinyi Okonjo

Theses, Dissertations and Capstones

Introduction: Controlled substances have been described as pharmaceuticals or illegal medicines that act primarily on the central nervous system and could cause physical and mental dependence, eventually leading to addiction. Prescription opioids were a significant contributor to the opioid epidemic, accounting for more than 70,000 opioid-related overdose deaths, including illicit and prescription opioids, between 2018 and 2019. The Electronic Prescriptions for Controlled Substances (EPCS) initiative recently aimed to reduce rates of prescription opioid addiction, abuse, diversion, and death. The system for controlled substances had become more widely used as providers and governments trying to combat the opioid problem. Because …


Mechanisms Of Apoptosis Induced By Actinomycin D In Aerodigestive Tract Cancers, Adeoluwa Ayodeji Adeluola Jan 2021

Mechanisms Of Apoptosis Induced By Actinomycin D In Aerodigestive Tract Cancers, Adeoluwa Ayodeji Adeluola

Theses, Dissertations and Capstones

Upper aerodigestive tract cancers including cancers of the oral cavity, pharynx, larynx, esophagus, and lungs are the most prevalent cancers and leading causes of cancer-related deaths. Collectively, over 300,000 new cases and 146,500 deaths are projected within the US in the year 2021. Drug-associated toxicities, as well as resistance to therapy (intrinsic and acquired), are big challenges for successfully treating these cancers. Recent studies have shown that combining low-dose actinomycin D with existing therapies is a promising strategy to reduce toxicity (cyclotherapy) and to overcome resistance. The development of these treatment strategies however requires an understanding of the molecular mechanisms …


Characterization Of Cardiovascular Function In Adult Offspring Following Prenatal Exposure To Methamphetamine, Hasitha Chavva Jan 2021

Characterization Of Cardiovascular Function In Adult Offspring Following Prenatal Exposure To Methamphetamine, Hasitha Chavva

Theses, Dissertations and Capstones

Methamphetamine (meth) is a synthetic stimulant, and its abuse is a significant public health concern in the United States and all over the world. Methamphetamine is a highly addictive drug, and its abuse is widespread among women of child-bearing age. The consequences of methamphetamine abuse are not only of relevance to pregnant women, but also their unborn children, as amphetamine type substances can cross the placental barrier and effect the fetus during gestation. Most previous studies investigating the impact of prenatal methamphetamine exposure on the offspring have focused on neurological and behavioral effects. The goal of this study was to …


Consider Real Costs Before Implementing A 340b Program, Kenneth Maxik, Craig Kimble, Alberto Coustasse Sep 2020

Consider Real Costs Before Implementing A 340b Program, Kenneth Maxik, Craig Kimble, Alberto Coustasse

Pharmacy Practice & Administration

The 340B drug pricing program was created to improve access to outpatient medications for low-income and underinsured r uninsured patients. It has exponentially grown with the expansion of the definition of a covered entity and the change to allow multiple contract pharmacies. Still, there are debates about the program’s financial impact and whether the discounts are passed along to enough underinsured or uninsured patients.


Beyond Single Nucleotide Polymorphisms: Cyp3a5∗3 ∗6 ∗7 Composite And Abcb1 Haplotype Associations To Tacrolimus Pharmacokinetics In Black And White Renal Transplant Recipients, Daniel A. Brazeau, Kristopher Attwood, Calvin J. Meaney, Gregory E. Wilding, Joseph D. Consiglio, Shirley S. Chang, Aijaz Gundroo, Rocco C. Venuto, Louise Cooper, Kathleen M. Tornatore Aug 2020

Beyond Single Nucleotide Polymorphisms: Cyp3a5∗3 ∗6 ∗7 Composite And Abcb1 Haplotype Associations To Tacrolimus Pharmacokinetics In Black And White Renal Transplant Recipients, Daniel A. Brazeau, Kristopher Attwood, Calvin J. Meaney, Gregory E. Wilding, Joseph D. Consiglio, Shirley S. Chang, Aijaz Gundroo, Rocco C. Venuto, Louise Cooper, Kathleen M. Tornatore

Pharmaceutical Science and Research

Interpatient variability in tacrolimus pharmacokinetics is attributed to metabolism by cytochrome P-450 3A5 (CYP3A5) isoenzymes and membrane transport by P-glycoprotein. Interpatient pharmacokinetic variability has been associated with genotypic variants for both CYP3A5 or ABCB1. Tacrolimus pharmacokinetics was investigated in 65 stable Black and Caucasian post-renal transplant patients by assessing the effects of multiple alleles in both CYP3A5 and ABCB1. A metabolic composite based upon the CYP3A5 polymorphisms: 3(rs776746), 6(10264272), and 7(41303343), each independently responsible for loss of protein expression was used to classify patients as extensive, intermediate and poor metabolizers. In addition, the …