Other Pharmacy and Pharmaceutical Sciences Commons^™

Effects Of Transition From Closed-Book To Open-Book Assessment On Students’ Scores In A Pharmacokinetics Course, Reza Mehvar, Richard Beuttler

Pharmacy Faculty Articles and Research

Closed-book summative assessment of student learning, common in pharmacy education, is challenging to administer in a remote setting due to the need for costly and intrusive monitoring technology. Therefore, open-book assessments without monitoring have been considered an alternative in remote settings. The present study investigated the effects of the transition from in-person closed-book to remote open-book format on the students’ scores in different assessment categories in a Pharmacokinetics course. The students’ performances in the transition cohort (Transition, n = 96) during the in-person and remote periods were compared with those of an in-person cohort (Control, n = 85) during the …

A New Method For Investigating Bioequivalence Of Inhaled Formulations: A Pilot Study On Salbutamol, Homa Razaei, Maryam Khoubnasabjafari, Vahid Jouyban-Gharamaleki, Hamed Hamishehkar, Mohammad Reza Afshar Mogaddam, Elaheh Rahimpour, Reza Mehvar, Abolghasem Jouyban

Pharmacy Faculty Articles and Research

Purpose: An efficient, cost-effective and non-invasive test is required to overcome the challenges faced in the process of bioequivalence (BE) studies of various orally inhaled drug formulations. Two different types of pressurized meter dose inhalers (MDI-1 and MDI-2) were used in this study to test the practical applicability of a previously proposed hypothesis on the BE of inhaled salbutamol formulations.

Methods: Salbutamol concentration profiles of the exhaled breath condensate (EBC) samples collected from volunteers receiving two inhaled formulations were compared employing BE criteria. In addition, the aerodynamic particle size distribution of the inhalers was determined by employing next generation impactor. …

Implementing Auc Monitoring In A Pharmacist-Managed Vancomycin Dosing Protocol: A Retrospective Cohort Study, Brandon L S Robinson, Blake Bennie, Mahmoud Nasiri, Kieu Nguyen, Reba Forbess, Mallory Gessner-Wharton, Cassie Robertson

HCA Healthcare Journal of Medicine

Background

Consensus guidelines on the therapeutic drug monitoring of vancomycin published in 2020 recognize that using the calculated area-under-the-curve (AUC) to guide dosing maximizes clinical efficacy and minimizes risk when compared to traditional trough-based dosing. The purpose of this study was to determine whether AUC monitoring results in reduced acute kidney injury (AKI) rates in adult patients receiving vancomycin for all indications.

Methods

In this study, patients 18 years or older who received pharmacist-managed vancomycin therapy were selected using pharmacy surveillance software from 2 timeframes. Patients were excluded if they received less than 48 hours of therapy or had unstable …

An Epidemiological And Pharmacokinetic-Pharmacodynamic Investigation Into The Impact Of Carbapenem-Resistant Enterobacterales, Justin Clark

Theses and Dissertations--Pharmacy

Background: According to the 2019 CDC Antibiotic Resistance Threats Report, more than 2.8 million antibiotic-resistant infections occur in the United States each year, leading to more than 35,000 deaths. Among the most urgent threats identified by the CDC are carbapenem-resistant Enterobacterales (CRE). Despite efforts to control the spread of these organisms, the number of estimated cases between 2012 and 2017 remained stable. In 2017, an estimated 13,100 hospitalized cases of CRE led to approximately 1,100 deaths and $130 million attributable healthcare costs. This dissertation seeks to address this issue from both a pharmacokinetic/pharmacodynamic and epidemiological perspective.

Methods: We evaluated the …

Preclinical Development Of A Novel Antileishmanial Agent Ojt007: Bioanalytical Assay, In Vitro Studies And Pharmacokinetics, Maria Eugenia Rincon-Nigro

Dissertations (2016-Present)

Current treatments for cutaneous leishmaniasis suffer from toxic side effects, high cost, parenteral administration, and drug resistance. Thus, there is a critical need to develop oral drugs for the treatment of leishmaniasis. OJT007 is a novel class of drug with potent antiproliferative effects against Leishmania Major. The purpose of this project is to conduct preclinical drug development studies for OJT007 including bioanalytical assay development, pre-formulation studies, in vitro hepatic drug metabolism and in vivo pharmacokinetics. A sensitive, specific, and reproducible ultra-high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated. The separation was achieved on a UPLC BEH …

A Meshless Approach To Computational Pharmacokinetics, Anthony Matthew Khoury

Doctoral Dissertations and Master's Theses

The meshless method is an incredibly powerful technique for solving a variety of problems with unparalleled accuracy and efficiency. The pharmacokinetic problem of transdermal drug delivery (TDDD) is one such topic and is of significant complexity. The locally collocated meshless method (LCMM) is developed in solution to this topic. First, the meshless method is formulated to model this transport phenomenon and is then validated against an analytical solution of a pharmacokinetic problem set, to demonstrate this accuracy and efficiency. The analytical solution provides a locus by which convergence behavior are evaluated, demonstrating the super convergence of the locally collocated meshless …

A Semi-Physiological Three-Compartment Model Describes Brain Uptake Clearance And Efflux Of Sucrose And Mannitol After Iv Injection In Awake Mice, Behnam Noorani, Ekram Ahmed Chowdhury, Faleh Alqahtani, Md Sanaullah Sajib, Yeseul Ahn, Ehsan Nozohouri, Dhavalkumar Patel, Constantinos Mikelis, Reza Mehvar, Ulrich Bickel

Pharmacy Faculty Articles and Research

Purpose

To evaluate a three-compartmental semi-physiological model for analysis of uptake clearance and efflux from brain tissue of the hydrophilic markers sucrose and mannitol, compared to non-compartmental techniques presuming unidirectional uptake.

Methods

Stable isotope-labeled [¹³C]sucrose and [¹³C]mannitol (10 mg/kg each) were injected as IV bolus into the tail vein of awake young adult mice. Blood and brain samples were taken after different time intervals up to 8 h. Plasma and brain concentrations were quantified by UPLC-MS/MS. Brain uptake clearance (K_in) was analyzed using either the single-time point analysis, the multiple time point graphical method, …

The Concentration Of Brain Homogenates With The Amicon Ultra Centrifugal Filters, Joshua Yang, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Accurately measuring the brain concentration of a neurotherapeutic is critical in determining its pharmacokinetic profile in vivo. Biologics are potential therapeutics for neurologic diseases and biologics fused to an antibody targeting a transcytosis receptor at the Blood-Brain Barrier, designated as antibody-biologic fusion proteins, are Blood-Brain Barrier penetrating neurotherapeutics. The use of sandwich immunosorbent assays to measure concentrations of antibody-biologic fusion proteins in brain homogenates has become increasingly popular. The raw brain homogenate contains many proteins and other macromolecules that can cause a matrix effect, potentially interfering with the limit of detection of such assays and reduce the overall sample …

Acute And Chronic Dosing Of A High-Affinity Rat/Mouse Chimeric Transferrin Receptor Antibody In Mice, Demi M. Castellanos, Jiahong Sun, Joshua Yang, Weijun Ou, Alexander C. Zambon, William M. Pardridge, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Non-invasive brain delivery of neurotherapeutics is challenging due to the blood-brain barrier. The revived interest in transferrin receptor antibodies (TfRMAbs) as brain drug-delivery vectors has revealed the effect of dosing regimen, valency, and affinity on brain uptake, TfR expression, and Fc-effector function side effects. These studies have primarily used monovalent TfRMAbs with a human constant region following acute intravenous dosing in mice. The effects of a high-affinity bivalent TfRMAb with a murine constant region, without a fusion partner, following extravascular dosing in mice are, however, not well characterized. Here we elucidate the plasma pharmacokinetics and safety of a high-affinity bivalent …

Epigenetic Regulation Of Drug Metabolizing Enzymes In Normal Aging, Mohamad M. Kronfol

Theses and Dissertations

Geriatric populations are at a higher risk for adverse drug reactions (ADRs). This may be partly due to changes in drug metabolism in old age, but the underlying mechanisms are poorly understood. Prior research in humans and mice has shown age-associated changes to the expression of several genes involved in drug metabolism. Furthermore, studies of human blood showed that epigenetic regulation of genes encoding drug metabolizing enzymes change with age. However, it is unknown if genes in the liver are similarly affected. Therefore, we hypothesize that genes encoding drug metabolizing enzymes may show differential epigenetic regulation in the liver with …

A Two Compartment Pharmacokinetic Model Describes The Intra‐Articular Delivery And Retention Of Rhprg4 Following Acl Transection In The Yucatan Mini Pig, Mark Hurtig, Iman Zaghoul, Heather Sheardown, Tannin A. Schmidt, Lina Liu, Ling Zhang, Khaled A. Elsaid, Gregory D. Jay

Pharmacy Faculty Articles and Research

Treatment of the injured joint with rhPRG4 is based on recent observations that inflammation diminishes expression of native PRG4. Re‐establishing lubrication between pressurized and sliding cartilage surfaces during locomotion promotes the nascent expression of PRG4 and thus intra‐articular (IA) treatment strategies should be supported by pharmacokinetic evidence establishing the residence time of rhPRG4. A total of 21 Yucatan minipigs weighing ∼55 Kg each received 4 mg of 131I‐rhPRG4 delivered by IA injection 5 days following surgical ACL transection. Animals were sequentially euthanized following IA rhPRG4 at 10 mins (time zero), 24, 72 hrs, 6, 13 and 20 days later. The …

Simultaneous Uplc–Ms/Ms Analysis Of Two Stable Isotope Labeled Versions Of Sucrose In Mouse Plasma And Brain Samples As Markers Of Blood-Brain Barrier Permeability And Brain Vascular Space, Ekram Ahmed Chowdhury, Saad Alqahtani, Raktima Bhattacharya, Reza Mehvar, Ulrich Bickel

Pharmacy Faculty Articles and Research

Blood Brain Barrier (BBB) permeability is frequently compromised in the course of diseases affecting the central nervous system (CNS). Sucrose is a low molecular weight, hydrophilic marker with low permeability at the naive BBB and therefore one of the widely used indicators of barrier integrity. Our laboratory recently developed a highly sensitive UPLC-MS/MS method for stable isotope labelled [13C12]sucrose in biological matrices. Correction of total brain concentration for contribution of intravascular space is required in such experiments in order to accurately measure BBB permeability, and it is often accomplished by vascular perfusion with buffer solutions prior to brain sampling. The …

Population Pharmacokinetics And Pharmacodynamics Of Extended-Infusion Piperacillin And Tazobactam In Critically Ill Children, Chad A. Knoderer, Kristen R. Nichols, Eun Kyoung Chung, Lauren E. Buenger, Daniel P. Healy, Jennifer Dees, Ashley S. Crumby, Michael B. Kays

Chad A. Knoderer

The study objective was to evaluate the population pharmacokinetics and pharmacodynamics of extended-infusion piperacillintazobactam in children hospitalized in an intensive care unit. Seventy-two serum samples were collected at steady state from 12 patients who received piperacillin-tazobactam at 100/12.5 mg/kg of body weight every 8 h infused over 4 h. Population pharmacokinetic analyses were performed using NONMEM, and Monte Carlo simulations were performed to estimate the piperacillin pharmacokinetic profiles for dosing regimens of 80 to 100 mg/kg of the piperacillin component given every 6 to 8 h and infused over 0.5, 3, or 4 h. The probability of target attainment (PTA) …

The Development Of Methods To Account For Physiologic Dynamic Changes And Their Effects On The Pharmacokinetics Of Therapeutic Monoclonal Antibodies And Other Therapeutics, Josiah Thomas Ryman

Theses and Dissertations (ETD)

Physiologic changes in the body can drastically affect the clearance of a medication, and therefore increase the variability in exposure to the medication. Physiologic changes that can have a profound effect on the exposure of a medication can stem from changes CYP enzymes, transport proteins, binding protein expression, organ function, immune reactivity, and health status to name a few; with the focus of this dissertation on the dynamic changes in the ontogeny of MRP2 (an apical liver transport protein) and the dynamic changes caused by an immune response to a therapeutic monoclonal antibody (mAb). Several approaches can be used to …

Population Pharmacokinetics And Pharmacodynamics Of Extended-Infusion Piperacillin And Tazobactam In Critically Ill Children, Chad A. Knoderer, Kristen R. Nichols, Eun Kyoung Chung, Lauren E. Buenger, Daniel P. Healy, Jennifer Dees, Ashley S. Crumby, Michael B. Kays

Scholarship and Professional Work – COPHS

The study objective was to evaluate the population pharmacokinetics and pharmacodynamics of extended-infusion piperacillintazobactam in children hospitalized in an intensive care unit. Seventy-two serum samples were collected at steady state from 12 patients who received piperacillin-tazobactam at 100/12.5 mg/kg of body weight every 8 h infused over 4 h. Population pharmacokinetic analyses were performed using NONMEM, and Monte Carlo simulations were performed to estimate the piperacillin pharmacokinetic profiles for dosing regimens of 80 to 100 mg/kg of the piperacillin component given every 6 to 8 h and infused over 0.5, 3, or 4 h. The probability of target attainment (PTA) …

Nanoformulation For Anticancer Drug Delivery: Enhanced Pharmacokinetics And Circulation, Gaurav Parekh

Doctoral Dissertations

In this study, we have explored the application of the Layer-by-Layer (LbL) assembly technique for improving injectable drug delivery systems of low soluble anticancer drugs (e.g. Camptothecin (CPT), Paclitaxel (PTX) or Doxorubicin (DOX)). For this study, a polyelectrolyte shell encapsulates different types of drug nanocores (e.g. soft core, nanomicelle or solid lipid nanocores).The low soluble drugs tend to crystallize and precipitate in an aqueous medium. This is the reason they cannot be injected and may have low concentrations and low circulation time in the blood. Even though these drugs when present in the cancer microenvironment have high anti-tumor inhibition, the …

Effects Of Pringle Maneuver And Partial Hepatectomy On The Pharmacokinetics And Blood–Brain Barrier Permeability Of Sodium Fluorescein In Rats, Mohammad K. Miah, Imam H. Shaik, Ulrich Bickel, Reza Mehvar

Pharmacy Faculty Articles and Research

Liver diseases are known to affect the function of remote organs. The aim of the present study was to investigate the effects of Pringle maneuver, which results in hepatic ischemia–reperfusion (IR) injury, and partial hepatectomy (Hx) on the pharmacokinetics and brain distribution of sodium fluorescein (FL), which is a widely used marker of blood–brain barrier (BBB) permeability. Rats were subjected to Pringle maneuver (total hepatic ischemia) for 20 min with (HxIR) or without (IR) 70% hepatectomy. Sham-operated animals underwent laparotomy only. After 15 min or 8 h of reperfusion, a single 25-mg/kg dose of FL was injected intravenously and serial …

Effects Of Hepatic Ischemia-Reperfusion Injury On The P-Glycoprotein Activity At The Liver Canalicular Membrane And Blood-Brain Barrier Determined By In Vivo Administration Of Rhodamine 123 In Rats, M. K. Miah, Imam H. Shaik, Ulrich Bickel, Reza Mehvar

Pharmacy Faculty Articles and Research

Purpose To investigate the effects of normothermic hepatic ischemia-reperfusion (IR) injury on the activity of P-glycoprotein (P-gp) in the liver and at the blood-brain barrier (BBB) of rats using rhodamine 123 (RH-123) as an in vivo marker.

Methods Rats were subjected to 90 min of partial ischemia or sham surgery, followed by 12 or 24 h of reperfusion. Following intravenous injection, the concentrations of RH-123 in blood, bile, brain, and liver were used for pharmacokinetic calculations. The protein levels of P-gp and some other transporters in the liver and brain were also determined by Western blot analysis.

Results P-gp protein …

The Pharmacokinetics Of Metal-Based Engineered Nanomaterials, Focusing On The Blood-Brain Barrier, Mo Dan

Theses and Dissertations--Pharmacy

Metal-based engineered nanomaterials (ENMs) have potential to revolutionize diagnosis, drug delivery and manufactured products, leading to greater human ENM exposure. It is crucial to understand ENM pharmacokinetics and their association with biological barriers such as the blood-brain barrier (BBB). Physicochemical parameters such as size and surface modification of ENMs play an important role in ENM fate, including their brain association. Multifunctional ENMs showed advantages across the highly regulated BBB. There are limited reports on ENM distribution among the blood in the brain vasculature, the BBB, and brain parenchyma.

In this study, ceria ENM was used to study the effect of …

High Dose Simvastatin As A Potential Anticancer Therapy In Leukemia Patients, Tamer Ahmed

Theses and Dissertations--Pharmacy

Simvastatin is a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor that is used for the treatment of hyperlipidemia. Simvastatin has recently been studied for its potential use in cancer therapy. In-vitro studies have shown that simvastatin displays anticancer activity, but at concentrations unlikely to be achieved in patients being receiving typical antihyperlipidemic treatment doses. Thus, several clinical trials were conducted to study the tolerability of high dose statins in cancer patients. The maximum tolerated dose of simvastatin was determined to be 15 mg/kg/day, 25-fold higher than a typical dose. However, it is not known if simvastatin plasma concentrations can reach those …

Pharmacokinetic/Pharmacodynamic (Pk/Pd) Modeling Of Anti-Neoplastic Agents, Daniel Lexcen, Ahmed H. Salem, Walid F. Elkhatib, Virginia Haynes, Ayman Noreddin

Pharmacy Faculty Books and Book Chapters

"Development of tumor resistance to chemotherapeutics is related to inherent tumor variations regarding sensitivity to chemotherapeutics and to sub-optimal dosing regimens, including variation in patient pharmacokinetics that result in suboptimal exposure of tumor cells to anti-neoplastic drugs [1, 2]. The rate and extent of drug efficacy depends on the extent of drug exposure at the tumor site and the time above the effective concentration [3]. In vitro models that incorporate these pharmacokinetic and pharmacodynamic (PK/PD) principles to optimize therapeutic response may be considered the method of choice for optimizing dosing schedules before translating data from static assays to animals and …

Application Of Pharmacokinetics/Pharmacodynamics (Pk/Pd) In Designing Effective Antibiotic Treatment Regimens, Ghada F. Ahmed, Ayman Noreddin

Pharmacy Faculty Books and Book Chapters

"Designing antibiotic dosing regimens is often not optimal and the dose-response relationship for most antibiotics is not well-known1. Both Pharmacokinetics (PK) and Pharmacodynamics (PD) are characteristics of antimicrobial agents that should be considered in the development of effective antibiotic therapy. By linking the concentration time profile at the site of action to the drug effect (PK/PD), the effect of varying dosage regimens against pathogens could be simulated enabling the identification of effective dosage strategies. It is known that inadequate antibiotic dosing could not only lead to a therapeutic failure, but also to the development of bacterial resistance. Importantly, the evolution …

Effects Of Simulations On The Learning Of Pharmacokinetic Concepts, Reza Mehvar

Pharmacy Faculty Articles and Research

Objective: Although the use of computer simulations in pharmacokinetics courses is not new, the data on the effects of simulation on student learning are scarce. The objective of this study was to design and evaluate the use of Web-based simulations on the learning of pharmacokinetic concepts by doctor of pharmacy (PharmD) students.

Method: Six online modules were designed to allow the instructor and students to use “what-if” scenarios for understanding the effects of various dosage regimens and/or pharmacokinetic parameters on the plasma concentration-time courses of drugs. The designed modules were intravenous and oral pharmacokinetic concepts, bioavailability, intravenous infusion, …

Dextran-Methylprednisolone Succinate As A Prodrug Of Methylprednisolone: Plasma And Tissue Disposition, Xiaoping Zhang, Reza Mehvar

Pharmacy Faculty Articles and Research

Plasma and tissue disposition of a macromolecular prodrug of methylprednisolone (MP), dextran (70 kDa)–methylprednisolone succinate (DMP), was studied in rats. Single 5‐mg/kg doses of DMP or unconjugated MP were administered into the tail veins of different groups of rats (n  = 4/group/time point). Blood (cardiac puncture) and tissues (liver, spleen, kidney, heart, lung, thymus, and brain) were collected at various times after DMP (0–96 h) or MP (0–2 h) injections. Concentrations of DMP and MP in samples were analyzed by size‐exclusion chromatography (SEC) and reversed‐phase high‐performance liquid chromatography (HPLC), respectively. Conjugation of MP with 70‐kDa dextran resulted in 22‐, …