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Pharmacokinetics

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Full-Text Articles in Pharmacy and Pharmaceutical Sciences

An Evaluation Of Artificial Intelligence Chatbots As Alternatives To Specialized Software In Teaching Bayesian Pharmacokinetic Analysis, Reza Mehvar May 2026

An Evaluation Of Artificial Intelligence Chatbots As Alternatives To Specialized Software In Teaching Bayesian Pharmacokinetic Analysis, Reza Mehvar

Pharmacy Faculty Articles and Research

Objective

To investigate the accuracy and reliability of artificial intelligence chatbots in estimating pharmacokinetic parameters from limited patient samples and population data for potential application in teaching Bayesian concepts.

Methods

Two plasma concentration–time data sets after a single intravenous dose, along with population values for volume of distribution (V) and elimination rate constant (k), were entered into free versions of ChatGPT and Gemini. Three prompts were engineered to assess and improve the accuracy and consistency of patient-only (based on plasma concentrations) and Bayesian (based on plasma concentrations and population data) estimates of V and k. …


Brief Review: Does Red Hair Phenotype Affect Propofol Pharmacokinetics Or Pharmacodynamics?, James Espinosa, Frank Wheeler, Robin Lahr, Sergey Medlenov, Alan Lucerna May 2026

Brief Review: Does Red Hair Phenotype Affect Propofol Pharmacokinetics Or Pharmacodynamics?, James Espinosa, Frank Wheeler, Robin Lahr, Sergey Medlenov, Alan Lucerna

Rowan-Virtua Research Day

Background: A persistent belief within Emergency Medicine and perioperative culture suggests that individuals with red hair require altered anesthetic dosing. While early studies demonstrated increased requirements for certain volatile anesthetics in red-haired individuals, this association is frequently generalized to propofol without clear supporting evidence.

Objective: To review current literature regarding the relationship between red hair phenotype (and MC1R variants) and propofol pharmacokinetics (PK) and pharmacodynamics (PD).

Methods: A focused narrative review of controlled human studies and relevant clinical outcome data evaluating propofol PK and PD in red-haired individuals.

Results: Evidence supporting altered anesthetic requirement in red-haired individuals primarily derives from …


Molecular Survival Strategies Against Kidney Filtration: Implications For Therapeutic Protein Engineering, William Heaps, Anna Elise Packard, Kristina M. Mccammon, Tyler P. Green, Joseph P. Talley, Bradley C. Bundy, Dennis Della Corte Jan 2026

Molecular Survival Strategies Against Kidney Filtration: Implications For Therapeutic Protein Engineering, William Heaps, Anna Elise Packard, Kristina M. Mccammon, Tyler P. Green, Joseph P. Talley, Bradley C. Bundy, Dennis Della Corte

Faculty Publications

The glomerular filtration barrier poses a significant challenge for circulating proteins, with molecules below ~60–70 kDa facing rapid renal clearance. Endogenous proteins have evolved sophisticated evasion mechanisms including oligomerization, carrier binding, electrostatic repulsion, and FcRn-mediated recycling. Understanding these natural strategies provides blueprints for engineering therapeutic proteins with improved pharmacokinetics. This review examines how endogenous proteins resist filtration, evaluates their application in protein engineering, and discusses clinical translation including established technologies (PEGylation, Fc-fusion) and emerging strategies (albumin-binding domains, glycoengineering). We address critical challenges of balancing half-life extension with tissue penetration, biological activity, and immunogenicity—essential considerations for the rational design of next-generation …


Dupilumab For The Treatment Of Prurigo Nodularis, Iain Noel Encarnacion, Noelle Desir, Simona A. Alomary, Nicole Baker Jan 2026

Dupilumab For The Treatment Of Prurigo Nodularis, Iain Noel Encarnacion, Noelle Desir, Simona A. Alomary, Nicole Baker

SKMC Student Presentations and Publications

Prurigo nodularis (PN) is a chronic, intensely pruritic dermatosis driven by neural and immune dysregulation, with historically limited FDA-approved treatment options. In September 2022, dupilumab became the first FDA-approved therapy for PN. To review the clinical efficacy of dupilumab in PN, with emphasis on pivotal clinical trials, real-world evidence, and safety profile. We examined mechanistic studies of dupilumab, early case reports and series, phase 3 LIBERTY-PN PRIME and PRIME2 randomized trials, real world observational studies, and safety data. Dupilumab, a human monoclonal antibody targeting IL-4Rα, suppresses type 2 inflammation. In PRIME (n = 151) and PRIME2 (n = 160), dupilumab …


Longitudinal Pharmacokinetic And Safety Studies Of An Antibody-Erythropoietin Fusion Protein For Alzheimer's Disease, Rudy Chang, Devaraj Venkatapura Chandrashekar, G. Chuli Roules, Nataraj Jagadeesan, Emi Iwasaki, Adenike Oyegbesan, Hayk Davtyan, Rachita K. Sumbria Dec 2025

Longitudinal Pharmacokinetic And Safety Studies Of An Antibody-Erythropoietin Fusion Protein For Alzheimer's Disease, Rudy Chang, Devaraj Venkatapura Chandrashekar, G. Chuli Roules, Nataraj Jagadeesan, Emi Iwasaki, Adenike Oyegbesan, Hayk Davtyan, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Erythropoietin (EPO) shows promise for Alzheimer's disease (AD) but has poor brain penetration, necessitating high doses that cause hematopoietic side effects. To improve brain delivery, EPO was fused to a transferrin receptor monoclonal antibody (TfRMAb), and this study evaluated the pharmacokinetics (PK), safety, and efficacy of repeated TfRMAb-EPO dosing in mice to further its preclinical development. C57BL/6J male mice (10 weeks old, n = 4–5/dose) received subcutaneous (SQ) low (1 mg/kg), mid (3 and 6 mg/kg), or high (20 mg/kg) TfRMAb-EPO doses for 4 weeks. The 1 mg/kg dose showed no adverse effects and resulted in sustained brain and plasma …


In Vivo Pharmacokinetic Evaluation Of A Gastro-Retentive Triple Drug Delivery System Utilizing Natural Polymers For Enhanced Helicobacter Pylori Eradication, Edukulla Satheesh Kumar, Hindustan Abdul Ahad, Thirumalesh Naik Sugali Banoth Nov 2025

In Vivo Pharmacokinetic Evaluation Of A Gastro-Retentive Triple Drug Delivery System Utilizing Natural Polymers For Enhanced Helicobacter Pylori Eradication, Edukulla Satheesh Kumar, Hindustan Abdul Ahad, Thirumalesh Naik Sugali Banoth

Bulletin of Faculty of Pharmacy Cairo University

This study evaluates the in vivo pharmacokinetics of triple-drug gastro-retentive formulation (metronidazole- Plantago ovata seed mucilage/ clarithromycin- Abelmoschus esculentus fruit mucilage/enteric-coated pantoprazole) for Helicobacter pylori eradication, with a focus on pharmacokinetic parameters (e.g., relative bioavailability vs. conventional doses) as the true contribution. In a cross over study using six rabbits, plasma concentrations of metronidazole, clarithromycin, and pantoprazole sodium were measured via High Performance Liquid Chromatography technique, and pharmacokinetic parameters were determined. A single dose of the optimized formulation (C-8) produced optimal drug levels, with a mean Cmax of 24.36 ± 0.84 μg/mL and tmax at 6 hours. The other pharmacokinetic …


Effects Of Liver Surgery On Drug Transporters In The Liver And Remote Organs, Reza Mehvar Jul 2025

Effects Of Liver Surgery On Drug Transporters In The Liver And Remote Organs, Reza Mehvar

Pharmacy Faculty Articles and Research

Alterations in drug transporters in acute liver failure and chronic liver diseases, such as cirrhosis, have been reviewed before. However, there is a lack of comprehensive reviews on how liver surgery, including transplantation and partial hepatectomy, affects drug transporters. Because ischemia–reperfusion (IR) injury is a hallmark of liver transplantation and most other surgical procedures of the liver, this review focuses on the effects of IR injury, in addition to liver resection, on the expression and function of transporters in the liver and remote organs. Most of the reported studies in this area are carried out in animal models of liver …


Characterization Of Population Pharmacokinetics And Associated Interindividual Variability Of Drugs Used In Mass Drug Administration Against Lymphatic Filariasis, Abdullah Alshehri Aug 2024

Characterization Of Population Pharmacokinetics And Associated Interindividual Variability Of Drugs Used In Mass Drug Administration Against Lymphatic Filariasis, Abdullah Alshehri

Theses & Dissertations

Lymphatic filariasis (LF) is a mosquito-borne filarial infection that affects the lymphatic system. The progression of the disease is associated with severe comorbidities and social stigma among patients. The World Health Organization has categorized the disease as a public health problem, and it has been targeted by mass drug administration (MDA) campaigns over the past two decades. Several preventive chemotherapies have been used in MDA campaigns against LF, including a combination of three anti-filarial drugs (IDA therapy): albendazole (ALB), diethylcarbamazine (DEC), and ivermectin (IVM). Other antiparasitic drugs, such as moxidectin (MOX), are still under investigation for their activity against LF. …


An Ex-Vivo Investigation Of The Effect Of Skin Conditioning With Formulation Vehicles On The Dermal Disposition Of Diphenhydramine Perfused Directly Into The Dermis, Nasim Rezvani Haghighi Shirazi Jan 2024

An Ex-Vivo Investigation Of The Effect Of Skin Conditioning With Formulation Vehicles On The Dermal Disposition Of Diphenhydramine Perfused Directly Into The Dermis, Nasim Rezvani Haghighi Shirazi

Selected Full-Text Dissertations 2020-

It is well known that the composition/excipients of a topical dermatological drug product (TDDP) affect the permeation of an active pharmaceutical ingredient (API) through the skin. While it is generally accepted that the vehicle mostly modulates the release of the API from the product, little is known whether the vehicle might also influence the kinetics of the API within the skin itself. In one attempt to answer this question, we developed an ex-vivo model using pig ear and a retrodialysis/microdialysis technique to deliver the API directly into dermis and measure the API dermal pharmacokinetics (dPK). We compared the dPK of …


Biological Activity Of Rats Treated With Riboflavin In Polymeric Plga As Injectable Form, Sarah A. Hamood, Jabar A. Faraj, Ziad T. Al-Dahan Oct 2023

Biological Activity Of Rats Treated With Riboflavin In Polymeric Plga As Injectable Form, Sarah A. Hamood, Jabar A. Faraj, Ziad T. Al-Dahan

Al-Esraa University College Journal for Medical Sciences

The current study aims to optimize a fast, reproducible, reliable, and effective technique for estimating the biological activity of Vitamin B2 in injectable dose form using reversed-phase high-performance liquid chromatography (RP-HPLC). A biodegradable polymer, PLGA (Poly (lactic-co-glycolic acid) 50:50 type, approved as an active ingredient for parenteral administration, was used to load the vitamin in the injection volume of 1mg. Rats, both male and female, were employed as the animal models. Each animal was hosted for a duration of 40 days, and the activity of vitamin B2 was monitored at rapid intervals over six weeks using an HPLC device on …


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 …


The Roles Of Cyp1a2 And Cyp2d In Pharmacokinetic Profiles Of Serotonin And Norepinephrine Reuptake Inhibitor Duloxetine And Its Metabolites In Mice, Xuan Qin, Cen Xie, John M Hakenjos, Kevin R Mackenzie, Shelton R Boyd, Mercedes Barzi, Karl-Dimiter Bissig, Damian W Young, Feng Li Feb 2023

The Roles Of Cyp1a2 And Cyp2d In Pharmacokinetic Profiles Of Serotonin And Norepinephrine Reuptake Inhibitor Duloxetine And Its Metabolites In Mice, Xuan Qin, Cen Xie, John M Hakenjos, Kevin R Mackenzie, Shelton R Boyd, Mercedes Barzi, Karl-Dimiter Bissig, Damian W Young, Feng Li

Faculty, Staff and Students Publications

Duloxetine (DLX) is widely used to treat major depressive disorder. Little is known about the mechanistic basis for DLX-related adverse effects (e.g., liver injury). Human CYP1A2 and CYP2D6 mainly contributes to DLX metabolism, which was proposed to be involved in its adverse effects. Here, we investigated the roles of Cyp1a2 and Cyp2d on DLX pharmacokinetic profile and tissue distribution using a Cyp1a2 knockout (Cyp1a2-KO) mouse model together with a Cyp2d inhibitor (propranolol). Cyp1a2-KO has the few effects on the systematic exposure (area under the plasma concentration-time curve, AUC) and tissue disposition of DLX and its primary metabolites. Propranolol dramatically increased …


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, …


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 …


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 (ETD)

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 …


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 …