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Pharmacokinetics

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Full-Text Articles in Pharmacy and Pharmaceutical Sciences

Effects Of Transition From Closed-Book To Open-Book Assessment On Students’ Scores In A Pharmacokinetics Course, Reza Mehvar, Richard Beuttler Aug 2023

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 …


Development And Validation Of A Uplc-Ms/Ms Method To Investigate The Plasma Pharmacokinetics Of A KCa2.2/KCa2.3 Positive Allosteric Modulator In Mice, Mohammad Asikur Rahman, Devaraj Venkatapura Chandrashekar, Young-Woo Nam, Basir Syed, David Salehi, Hamidreza Montazeri Aliabadi, Miao Zhang, Reza Mehvar May 2023

Development And Validation Of A Uplc-Ms/Ms Method To Investigate The Plasma Pharmacokinetics Of A KCa2.2/KCa2.3 Positive Allosteric Modulator In Mice, Mohammad Asikur Rahman, Devaraj Venkatapura Chandrashekar, Young-Woo Nam, Basir Syed, David Salehi, Hamidreza Montazeri Aliabadi, Miao Zhang, Reza Mehvar

Pharmacy Faculty Articles and Research

Rationale

There is currently no treatment for spinocerebellar ataxias (SCAs), which are a group of genetic disorders that often cause a lack of coordination, difficulty walking, slurred speech, tremors, and eventually death. Activation of KCa2.2/KCa2.3 channels reportedly exerts beneficial effects in SCAs. Here, we report the development and validation of an analytical method for quantitating a recently-developed positive allosteric modulator of KCa2.2/KCa2.3 channels (compound 2q) in mouse plasma.

Methods

Mouse plasma samples (10 μL) containing various concentrations of 2q were subjected to protein precipitation in the presence of a structurally similar internal …


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 May 2023

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 Apr 2023

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 Jan 2023

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 …


Methylone And Mdma Pharmacokinetics Following Controlled Administration In Humans, Lourdes Poyatos, Alfredo Fabrizio Lo Faro, Diletta Berardinelli, Giorgia Sprega, Sara Malaca, Simona Pichini, Marilyn A. Huestis, Esther Papaseit, Clara Pérez-Mañá, Francesco Paolo Busardò, Magí Farré Nov 2022

Methylone And Mdma Pharmacokinetics Following Controlled Administration In Humans, Lourdes Poyatos, Alfredo Fabrizio Lo Faro, Diletta Berardinelli, Giorgia Sprega, Sara Malaca, Simona Pichini, Marilyn A. Huestis, Esther Papaseit, Clara Pérez-Mañá, Francesco Paolo Busardò, Magí Farré

Institute of Emerging Health Professions Faculty Papers

The aim of this study is to define, for the first time, human methylone and HMMC plasma pharmacokinetics following controlled administration of 50–200 mg methylone to 12 male volunteers. A new LC-MS/MS method was validated to quantify methylone, MDMA, and their metabolites in plasma. The study was a randomized, cross-over, double-blinded and placebo-controlled study, with a total of 468 plasma samples collected. First, 10 µL of MDMA-d5, MDA-d5 and methylone-d3 internal standards were added to 100 µL of plasma. Two mL of chloroform and ethyl acetate 9:1 (v/v) were then added, mixed well and centrifuged. The supernatant was fortified with …


Comparative Single Dose Pharmacokinetics And Metabolism Of Racemic Primaquine And Its Enantiomers In Human Volunteers, Washim Khan, Yan Hong Wang, Narayan D. Chaurasiya, Np Dhammika Nanayakkara Aug 2022

Comparative Single Dose Pharmacokinetics And Metabolism Of Racemic Primaquine And Its Enantiomers In Human Volunteers, Washim Khan, Yan Hong Wang, Narayan D. Chaurasiya, Np Dhammika Nanayakkara

Faculty and Student Publications

Primaquine (PQ) is a racemic drug used in treatment of malaria for six decades. Recent studies suggest that the two enantiomers of PQ are differentially metabolized in animals, and this results in different pharmacological and toxicological profiles. The current study characterizes the pharmacokinetic (PK) properties, metabolism and tolerability of the individual enantiomers of PQ in healthy human volunteers with normal glucose-6-phosphate dehydrogenase (G6PD) activity. Two cohorts (at two dose levels), each with 18 subjects, participated in three study arms in a crossover fashion: a single dose of the (−)-R enantiomer (RPQ), a single dose of the (+)-S enantiomer (SPQ), and …


The Development Of A Brain Penetrating Erythropoietin For The Treatment Of Alzheimer’S Disease, Joshua Yang May 2022

The Development Of A Brain Penetrating Erythropoietin For The Treatment Of Alzheimer’S Disease, Joshua Yang

KGI Theses and Dissertations

The development of a neurotherapeutic for the treatment of Alzheimer’s Disease (AD) is challenging due to limited endpoint efficacy. Erythropoietin (EPO), a hematopoietic neurotrophin, is a potential therapeutic for AD but has limited blood-brain barrier (BBB) permeability. A chimeric fusion protein of EPO bound to the transferrin receptor monoclonal antibody (cTfRMAb) can act as a molecular trojan horse for brain drug delivery, shuttling EPO into the brain via the transvascular route. However, cTfRMAbs have Fc-effector function adverse effects, and removal of the Fc N-linked glycosylation site by substituting Asn with Gly (cTfRMAb-N292G-EPO) reduces this Fc effector function. Hence, developing this …


Preclinical Development Of A Novel Antileishmanial Agent Ojt007: Bioanalytical Assay, In Vitro Studies And Pharmacokinetics, Maria Eugenia Rincon-Nigro May 2022

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 Apr 2022

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 …


Risk Of Opioid Overdose Associated With Concomitant Use Of Oxycodone And Selective Serotonin Reuptake Inhibitors, Ismaeel Yunusa, Joshua J. Gagne, Kazuki Yoshida, Katsiaryna Bykov Feb 2022

Risk Of Opioid Overdose Associated With Concomitant Use Of Oxycodone And Selective Serotonin Reuptake Inhibitors, Ismaeel Yunusa, Joshua J. Gagne, Kazuki Yoshida, Katsiaryna Bykov

Faculty Publications

Importance Some selective serotonin reuptake inhibitors (SSRIs) inhibit the enzymes responsible for the metabolism of oxycodone, a potent prescription opioid. The clinical consequences of this interaction on the risk of opioid overdose have not been elucidated.

Objective To compare opioid overdose rates in patients initiating oxycodone while taking SSRIs that are potent inhibitors of the cytochrome-P450 2D6 enzyme (CYP2D6) vs SSRIs that are not.

Design, Setting, and Participants This cohort study included adults who initiated oxycodone while receiving SSRI therapy between 2000 and 2020 whose data were included in 3 US health insurance databases.

Exposures Use of SSRIs that strongly …


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 Feb 2022

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 (Kin) was analyzed using either the single-time point analysis, the multiple time point graphical method, …


Exploiting Modulation Of The Blood-Brain And Blood-Tumor Barrier Permeability By Translational Focused Ultrasound For Therapeutic Delivery To Cns Metastases, Tasneem A. Arsiwala Jan 2022

Exploiting Modulation Of The Blood-Brain And Blood-Tumor Barrier Permeability By Translational Focused Ultrasound For Therapeutic Delivery To Cns Metastases, Tasneem A. Arsiwala

Graduate Theses, Dissertations, and Problem Reports

Transcranial low-intensity focused ultrasound is a unique technology to modulate the integrity of tight endothelial junctions and transiently increase BBB/BTB permeability to enhance therapeutic delivery. Despite promising early studies, present literature lacks agreement on key experimental conditions, which restricts our knowledge and the technique's widespread translation. This dissertation first provides a critical review of the current gaps in knowledge regarding the universal use of LiFUS in preclinical and clinical use. We then identify key parameters for translational and predictable opening of the BBB using a 3T MRI coupled with a clinical device. Our investigation highlights that passive permeability of the …


Direct Nose To The Brain Nanomedicine Delivery Presents A Formidable Challenge, Robert A. Yokel Dec 2021

Direct Nose To The Brain Nanomedicine Delivery Presents A Formidable Challenge, Robert A. Yokel

Pharmaceutical Sciences Faculty Publications

This advanced review describes the anatomical and physiological barriers and mechanisms impacting nanomedicine translocation from the nasal cavity directly to the brain. There are significant physiological and anatomical differences in the nasal cavity, olfactory area, and airflow reaching the olfactory epithelium between humans and experimentally studied species that should be considered when extrapolating experimental results to humans. Mucus, transporters, and tight junction proteins present barriers to material translocation across the olfactory epithelium. Uptake of nanoparticles through the olfactory mucosa and translocation to the brain can be intracellular via cranial nerves (intraneuronal) or other cells of the olfactory epithelium, or extracellular …


The Concentration Of Brain Homogenates With The Amicon Ultra Centrifugal Filters, Joshua Yang, Rachita K. Sumbria Nov 2021

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 …


Comparative Neuropharmacology And Pharmacokinetics Of Methamphetamine And Its Thiophene Analog Methiopropamine In Rodents, Silja Skogstad Tuv, Marianne Skov-Skov Bergh, Jannike Mørch Andersen, Synne Steinsland, Vigdis Vindenes, Michael H Baumann, Marilyn A. Huestis, Inger Lise Bogen Nov 2021

Comparative Neuropharmacology And Pharmacokinetics Of Methamphetamine And Its Thiophene Analog Methiopropamine In Rodents, Silja Skogstad Tuv, Marianne Skov-Skov Bergh, Jannike Mørch Andersen, Synne Steinsland, Vigdis Vindenes, Michael H Baumann, Marilyn A. Huestis, Inger Lise Bogen

Institute of Emerging Health Professions Faculty Papers

Methiopropamine is a novel psychoactive substance (NPS) that is associated with several cases of clinical toxicity, yet little information is available regarding its neuropharmacological prop-erties. Here, we employed in vitro and in vivo methods to compare the pharmacokinetics and neu-robiological effects of methiopropamine and its structural analog methamphetamine. Methiopro-pamine was rapidly distributed to the blood and brain after injection in C57BL/6 mice, with a phar-macokinetic profile similar to that of methamphetamine. Methiopropamine induced psychomotor activity, but higher doses were needed (Emax 12.5 mg/kg; i.p.) compared to methamphetamine (Emax 3.75 mg/kg; i.p.). A steep increase in locomotor activity was seen after …


Preparation And In Vitro/In Vivo Evaluation Of Orally Disintegrating/Modified-Release Praziquantel Tablets, Xuemei Wen, Zhaoyou Deng, Yangfeng Xu, Guoqing Yan Oct 2021

Preparation And In Vitro/In Vivo Evaluation Of Orally Disintegrating/Modified-Release Praziquantel Tablets, Xuemei Wen, Zhaoyou Deng, Yangfeng Xu, Guoqing Yan

Faculty and Student Publications

This study was designed to develop orally disintegrating/sustained-release praziquantel (PZQ) tablets using the hot-melt extrusion (HME) technique and direct compression, and subse-quently evaluate their release in in vitro and in vivo pharmacokinetics. For the extrusion process, hypromellose acetate succinate (HPMCAS)-LG was the carrier of pure PZQ, with a standard screw configuration used at an extrusion temperature of 140◦ C and a screw rotation speed of 100 rpm. Differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), powder X-ray diffraction (PXRD) and Fourier-transform infrared spectroscopy (FTIR) were performed to characterize the extru-date. Orally disintegrating/sustained-release praziquantel tablets (PZQ ODSRTs) were prepared by direct compression …


Double-Coated Biodegradable Poly (Butyl Cyanoacrylate) Nanoparticulate Delivery Systems For Brain Targeting Of Doxorubicin Via Oral Administration, Neeraj Kaushal Jan 2021

Double-Coated Biodegradable Poly (Butyl Cyanoacrylate) Nanoparticulate Delivery Systems For Brain Targeting Of Doxorubicin Via Oral Administration, Neeraj Kaushal

Theses and Dissertations

Primary brain cancer cells grow within the brain or cancer cells can metastasis from different site of the body into brain. The major hurdle in the treatment of brain cancer is the presence of blood-brain barrier (BBB). Additionally, acquired multidrug-resistant (MDR) impedes the success of long-term chemotherapy. Therefore, the objective of this investigation is to evaluate the brain targeting potential of orally administered poly(butyl cyanoacrylate) nanoparticulate delivery systems (PBCA-NPDS), double-coated with Tween 80 and polyethylene glycol (PEG) 20000 for brain delivery of doxorubicin, that does not cross the BBB by itself. And, evaluate the MDR reversal potential of PBCA-NPDS. Doxorubicin-loaded …


Ex Vivo Dermis Microdialysis: A Tool For Bioequivalence Testing Of Topical Dermatological Drug Product (Demonstration Of Proof Of Concept And Testing), Mohammad Asif Ali Jan 2021

Ex Vivo Dermis Microdialysis: A Tool For Bioequivalence Testing Of Topical Dermatological Drug Product (Demonstration Of Proof Of Concept And Testing), Mohammad Asif Ali

Selected Full-Text Dissertations 2020-

Clinical response to most topical dermatological drug products (TDDP) depends on the availability of the drug in the dermis. Dermal Microdialysis (dMD) is a sampling technique that permits measuring the concentration of a drug over time, in vivo, directly into the target tissue, the dermis. The pharmacokinetic parameters obtained from such studies may help to optimize the development of TDDP and potentially can be applied to the assessment of TDDP bioequivalence. However, these studies require several hours or even days of continuous sampling that makes it often stressful and unpractical for human subjects as well as animals. The goal of …


Apixaban Discontinuation For Invasive Or Major Surgical Procedures (Adios): A Prospective Cohort Study., Geno J. Merli, Walter K. Kraft, Luis H. Eraso, Taki Galanis, Lynda J. Thomson, Geoffrey O. Ouma, Eugene Viscusi, Jerald Z. Gong, Edwin Lam Jan 2021

Apixaban Discontinuation For Invasive Or Major Surgical Procedures (Adios): A Prospective Cohort Study., Geno J. Merli, Walter K. Kraft, Luis H. Eraso, Taki Galanis, Lynda J. Thomson, Geoffrey O. Ouma, Eugene Viscusi, Jerald Z. Gong, Edwin Lam

Department of Medicine Faculty Papers

Background

Apixaban pharmacokinetic properties and some clinical reports suggest cessation 48 hours prior to surgery is safe, but this has not been demonstrated in a naturalistic setting. We sought to measure the residual apixaban exposure in patients who had apixaban held as part of standard of care peri-operative management.

Methods

This was a prospective, observational study of patients in whom apixaban plasma concentration and anti-Xa activity were measured while at steady state apixaban dosing and again immediately prior to surgery. Clinical management of cessation and resumption of apixaban was at the discretion of the treating physician.

Results

One hundred and …


Clinically Relevant Interactions Between Atypical Antipsychotics And Anti-Infective Agents, Edoardo Spina, Maria Antonietta Barbieri, Giuseppe Cicala, Jose De Leon Dec 2020

Clinically Relevant Interactions Between Atypical Antipsychotics And Anti-Infective Agents, Edoardo Spina, Maria Antonietta Barbieri, Giuseppe Cicala, Jose De Leon

Psychiatry Faculty Publications

This is a comprehensive review of the literature on drug interactions (DIs) between atypical antipsychotics and anti-infective agents that focuses on those DIs with the potential to be clinically relevant and classifies them as pharmacokinetic (PK) or pharmacodynamic (PD) DIs. PubMed searches were conducted for each of the atypical antipsychotics and most commonly used anti-infective agents (13 atypical antipsychotics by 61 anti-infective agents/classes leading to 793 individual searches). Additional relevant articles were obtained from citations and from prior review articles written by the authors. Based on prior DI articles and our current understanding of PK and PD mechanism, we developed …


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 Sep 2020

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 …


First-In-Human Studies Of Mw01-6-189wh, A Brain-Penetrant, Antineuroinflammatory Small-Molecule Drug Candidate: Phase 1 Safety, Tolerability, Pharmacokinetic, And Pharmacodynamic Studies In Healthy Adult Volunteers, Linda J. Van Eldik, Lumy Sawaki, Karen Bowen, Daniel T. Laskowitz, Robert J. Noveck, Byron Hauser, Lynn Jordan, Tracy G. Spears, Huali Wu, Kevin Watt, Shruti Raja, Saktimayee M. Roy, D. Martin Watterson, Jeffrey T. Guptill Apr 2020

First-In-Human Studies Of Mw01-6-189wh, A Brain-Penetrant, Antineuroinflammatory Small-Molecule Drug Candidate: Phase 1 Safety, Tolerability, Pharmacokinetic, And Pharmacodynamic Studies In Healthy Adult Volunteers, Linda J. Van Eldik, Lumy Sawaki, Karen Bowen, Daniel T. Laskowitz, Robert J. Noveck, Byron Hauser, Lynn Jordan, Tracy G. Spears, Huali Wu, Kevin Watt, Shruti Raja, Saktimayee M. Roy, D. Martin Watterson, Jeffrey T. Guptill

Sanders-Brown Center on Aging Faculty Publications

MW01-6-189WH (MW189) is a novel central nervous system-penetrant small-molecule drug candidate that selectively attenuates stressor-induced proinflammatory cytokine overproduction and is efficacious in intracerebral hemorrhage and traumatic brain injury animal models. We report first-in-human, randomized, double-blind, placebo-controlled phase 1 studies to evaluate the safety, tolerability, and pharmacokinetics (PK) of single and multiple ascending intravenous doses of MW189 in healthy adult volunteers. MW189 was safe and well tolerated in single and multiple doses up to 0.25 mg/kg, with no clinically significant concerns. The most common drug-related treatment-emergent adverse event was infusion-site reactions, likely related to drug solution acidity. No clinically concerning changes …


Investigation Of Percutaneous Drug Pharmacokinetics In Yucatan Mini-Pig Utilizing Microdialysis: Development Of An In Vitro - In Vivo Relationship With Metronidazole Topical Dermatological Drug Products, Benjamin Alexander Kuzma Jan 2020

Investigation Of Percutaneous Drug Pharmacokinetics In Yucatan Mini-Pig Utilizing Microdialysis: Development Of An In Vitro - In Vivo Relationship With Metronidazole Topical Dermatological Drug Products, Benjamin Alexander Kuzma

Selected Full-Text Dissertations 2020-

The use of dermal microdialysis (dMD) to evaluate bioavailability (BA) and bioequivalence (BE) of topical dermatological drug products (TDDP) has shown promising results; however, studies conducted thus far have been inconclusive conceivably due to large inter- and intra-subject variability, in addition to the inability of short experiments to completely characterize the dermis pharmacokinetics (PK). By using multiple test sites on the same subject, and replicate probes at each test site, it is feasible to compare the dermal pharmacokinetics (dPK) of a drug from different products in parallel on the same subject, which in turn will help to control variability. Moreover, …


Epigenetic Regulation Of Drug Metabolizing Enzymes In Normal Aging, Mohamad M. Kronfol Jan 2020

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 …


Design, Synthesis, And Biological Evaluation Of Aryl Piperazines With Potential As Antidiabetic Agents Via The Stimulation Of Glucose Uptake And Inhibition Of Nadh:Ubiquinone Oxidoreductase, R. Devine, M. Kelada, S. Leonard, D.S.D. Martin, J.M.D. Walsh, C.J. Breen, R.B. Driver, Gemma K. Kinsella, J.B.C Findlay, J.C. Stephens Jan 2020

Design, Synthesis, And Biological Evaluation Of Aryl Piperazines With Potential As Antidiabetic Agents Via The Stimulation Of Glucose Uptake And Inhibition Of Nadh:Ubiquinone Oxidoreductase, R. Devine, M. Kelada, S. Leonard, D.S.D. Martin, J.M.D. Walsh, C.J. Breen, R.B. Driver, Gemma K. Kinsella, J.B.C Findlay, J.C. Stephens

Articles

The management of blood glucose levels and the avoidance of diabetic hyperglycemia are common objectives of many therapies in the treatment of diabetes. An aryl piperazine compound 3a (RTC1) has been described as a promoter of glucose uptake, in part through a cellular mechanism that involves inhibition of NADH:ubiquinone oxidoreductase. We report herein the synthesis of 41 derivatives of 3a (RTC1) and a systematic structure-activity-relationship study where a number of compounds were shown to effectively stimulate glucose uptake in vitro and inhibit NADH:ubiquinone oxidoreductase. The hit compound 3a (RTC1) remained the most efficacious with a 2.57 fold increase in glucose …


Pharmacokinetics Of Intraperitoneal Vancomycin In Patients On Automated Peritoneal Dialysis, Edwin Lam, Yi Ting Kayla Lien, Valvanera Vozmediano, Stephan Schmidt, Walter K. Kraft, Jingjing Zhang Sep 2019

Pharmacokinetics Of Intraperitoneal Vancomycin In Patients On Automated Peritoneal Dialysis, Edwin Lam, Yi Ting Kayla Lien, Valvanera Vozmediano, Stephan Schmidt, Walter K. Kraft, Jingjing Zhang

Department of Pharmacology and Experimental Therapeutics Posters

Primary Objective

  • Characterize the pharmacokinetics of vancomycin in plasma, dialysate, and urine following a single intraperitoneal dose

Secondary Objective

  • Explore the safety, tolerability, and feasibility in administering vancomycin during the long dwell period in patients on APD


Preclinical Evaluation Of An Unconventional Ruthenium‐Gold‐ Based Chemotherapeutic: Rance‐1, In Clear Cell Renal Cell Carcinoma, Benelita Elie, Karen Hubbard, Yuriy Pechenyy, Buddhadev Layek, Swayam Prabha, Maria Contel Jun 2019

Preclinical Evaluation Of An Unconventional Ruthenium‐Gold‐ Based Chemotherapeutic: Rance‐1, In Clear Cell Renal Cell Carcinoma, Benelita Elie, Karen Hubbard, Yuriy Pechenyy, Buddhadev Layek, Swayam Prabha, Maria Contel

Publications and Research

Background: There are few effective treatments for patients with advanced clear cell renal cell carcinoma (CCRCC). Recent findings indicate that ruthenium‐gold containing compounds exhibit significant antitumor efficacy against CCRCC in vitro affecting cell viability as well as angiogenesis and markers driving those 2 phenomena. However, no in vivo preclinical evaluation of this class of compounds has been reported.

Methods: Following the dose‐finding pharmacokinetic determination, NOD. CB17‐Prkdc SCID/J mice bearing xenograft CCRCC Caki‐1 tumors were treated in an intervention trial for 21 days at 10 mg/kg/72h of RANCE‐1. At the end of the trial, tumor samples were analyzed for histopathological and …


Assessment Of Antimicrobial Pharmacokinetics Curriculum In Schools And Colleges Of Pharmacy Across The United States, Gary Fong, Elias B. Chahine, Julie Ann Justo, Navaneeth Narayanan, Emily Heil, Kayla R. Stover, Jonathan C. Cho, Zach Jenkins, Conan Macdougall Jun 2019

Assessment Of Antimicrobial Pharmacokinetics Curriculum In Schools And Colleges Of Pharmacy Across The United States, Gary Fong, Elias B. Chahine, Julie Ann Justo, Navaneeth Narayanan, Emily Heil, Kayla R. Stover, Jonathan C. Cho, Zach Jenkins, Conan Macdougall

Pharmacy Practice Faculty Publications

No abstract provided.


Pharmacokinetics Of Ketamine At Dissociative Doses In An Adult Patient With Refractory Status Asthmaticus Receiving Extracorporeal Membrane Oxygenation Therapy., Edwin Lam, Ankit K. Rochani, Gagan Kaushal, Brandi N. Thoma, Julian Tanjuakio, Frances Mae West, Hitoshi Hirose Mar 2019

Pharmacokinetics Of Ketamine At Dissociative Doses In An Adult Patient With Refractory Status Asthmaticus Receiving Extracorporeal Membrane Oxygenation Therapy., Edwin Lam, Ankit K. Rochani, Gagan Kaushal, Brandi N. Thoma, Julian Tanjuakio, Frances Mae West, Hitoshi Hirose

Department of Pharmacology and Experimental Therapeutics Faculty Papers

PURPOSE: First-line management of severe asthma exacerbations include the use of inhaled short-acting β-agonists, anticholinergics, and systemic corticosteroids. Continuous intravenous ketamine given at dissociative doses may be a pharmacologic option in patients who are intubated with life-threatening severe bronchospasm unresponsive to standard therapy. We describe the case of a 44-year-old man admitted to the intensive care unit for status asthmaticus requiring intubation and mechanical ventilation.

METHODS: The patient developed severe refractory hypercapnic respiratory failure necessitating additional respiratory support with veno-venous extracorporeal membrane oxygenation (ECMO) therapy. Ketamine treatment was initiated at 0.5 mg/kg/h continuous infusion on the day of admission for …