Heterocyclic Compounds Commons^™

Colorectal Cancer: Differential Gene Expression And In Vitro Response To 5-Fluorouracil, Novel Fluoropyrimidine F10, And Potential Synergy With Lupeol, Shrey D. Thaker, Jenny Paredes, Jone Garai, Laura A. Martello, William H. Gmeiner, Jovanny Zabaleta, Jennie Williams

School of Medicine Faculty Publications

Colorectal cancer (CRC) remains one of the most lethal malignancies in the United States, with African American (AA) patients experiencing disproportionately higher incidence and mortality compared to Caucasian Americans (CAs). These disparities have been linked to tumor-intrinsic genomic differences, including microsatellite instability (MSI) and p53 mutation status, which may influence chemotherapeutic response, particularly to the standard-of-care agent 5-fluorouracil (5-FU). However, mechanistic insights have been limited by the lack of racially diverse preclinical models. Here, we evaluated the efficacy of F10 (a novel fluoropyrimidine polymer) vs. 5-FU using AA- and CA-derived CRC cell lines with distinct MSI and p53 profiles. MTT …

In Situ-Generated Volumetric Dried Plasma Spots For The Analysis Of Edaravone And Metabolites In Animal Models, Michele Protti, Roberta Di Lecce, Jiri Adamec, Luca G. Regazzoni, Valeria Valsecchi, Claudia Volpi, Roberto Mandrioli, Laura Mercolini

School of Graduate Studies Faculty Publications

In this study, for the first time rat plasma microsampling was carried out by means of in situ-generated volumetric dried plasma spot (vDPS) technology and applied to the determination of the neuroprotective agent edaravone and its sulphate and glucuronide metabolites. Sampling was performed using Telimmune® plasma separation cards (vPSC), which allow the formation of volumetrically accurate dried plasma spots (3 µL) from blood drops deposited on them. After accelerated forced drying and solvent extraction in methanol, drying and redissolution, analytes were baseline separated and quantified through an original HPLC-MS/MS analytical method. Validation assays provided excellent results, with detection limits between …

Real-World Impact Of Amiodarone On Apixaban Population Pharmacokinetics In Hospitalized Patients, Samantha Kolowrat, Chazmyn Riley, Kevin Lam, Lynda Thomson, Douglas F. Stickle, Walter K. Kraft

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Despite common coadministration in nonvalvular atrial fibrillation (NVAF), there is minimal evidence regarding the impact of concomitant amiodarone use on apixaban pharmacokinetics (PK). We described the population PK of apixaban (2.5 and 5mg twice daily) in 106 hospitalized patients with and without concomitant amiodarone administration at steady state. Apixaban PK was reasonably described by a one-compartment model with first-order absorption and linear elimination. Aside from the receipt of amiodarone, age was retained as a statistically significant covariate on apparent clearance. Model-based simulations depicted concomitant amiodarone use increasing AUCT for both 2.5mg (1.58, 90% CI [1.28, 1.87]) and 5mg (1.12, 90% …

Brivaracetam For Spinal Cord Injury-Related Neuropathic Pain: Results Of A Pilot Double-Blinded, Randomized, Placebo-Controlled Clinical Trial, Leslie R. Morse, Ricardo A. Battaglino, Nguyen Nguyen, Brian Devries, Abigail Welch, Ana Lucia Battaglino, Clas Linnman, Michael Stillman, Robert Wudlick, Joda Glossner, Grant Anderton, Richard Goldstein, Scott P. Falci

Department of Medicine Faculty Papers

OBJECTIVE: Assess feasibility, safety, and tolerability of 3 months of oral brivaracetam for severe (9-10/10) spinal cord injury-related neuropathic pain.

METHODS: We conducted a multisite pilot study where adults were randomized to 3 months of brivaracetam (100 mg BID) or placebo. Pain was assessed via the Brief Pain Inventory, the International Spinal Cord Injury Pain Basic Dataset (version 2.0), and a daily pain diary.

RESULTS: We enrolled 24 participants across 2 sites and 14 participants were included in the final analysis (n = 8 placebo, n = 6 brivaracetam). The drug was tolerated with expected, nonserious side effects (nausea if …

Cobenfy(Xanomeline/Trospium) Vs. Clozapine For Treatment-Resistant Schizophrenia, Harmann Singh, Akash M. Patel, Abdullah Noory, Kush C. Patel, Simran Gandhi

Rowan-Virtua Research Day

Background: Treatment-resistant schizophrenia (TRS) poses significant therapeutic challenges. Although clozapine remains the gold-standard pharmacologic treatment for TRS, its clinical utility is hampered by severe side effects and intensive monitoring requirements. KarXT (Cobenfy), a combination of xanomeline and trospium chloride, represents a novel antipsychotic approach by targeting muscarinic M1/M4 receptors instead of dopamine D2 pathways.

Hypothesis: KarXT offers comparable efficacy to clozapine with a more favorable safety and tolerability profile, making it a viable alternative for patients with TRS.

Methods: A systematic review was conducted to identify studies from 2015–2025 evaluating KarXT in schizophrenia. Sources included PubMed, ClinicalTrials.gov, FDA databases, ICER …

Identifying Early Presentation Of Serotonin Syndrome In A 20-Year-Old Male Prescribed Clomipramine And Quetiapine: A Case Report, Veronica Alday, Justin Scarano, Jonathan Yuh, Christie Richardson

Rowan-Virtua Research Day

Serotonin syndrome, a potentially life-threatening condition, can be challenging to diagnose due to its diverse etiology and varied symptomatology. Despite its severity, serotonin syndrome may present from mild to fatal, with symptoms such as autonomic instability, altered mental status, and neuromuscular excitation (e.g. muscle rigidity, hyperreflexia). Here, we present a 20-year-old male with an extensive psychiatric history who was prescribed clomipramine and developed serotonin syndrome. Few cases of serotonin syndrome have been reported to date, exacerbating the difficulty in recognizing and quickly treating such cases. Cases of serotonin syndrome should continue to be reported, in order to familiarize clinicians with …

Literature Review: Prazosin Used For Ptsd In Pregnancy, Afshan Khan, Natali Sharma, Rebekah M. Dietrich, Martin Forsberg

Rowan-Virtua Research Day

Posttraumatic Stress Disorder (PTSD) affects 3–4% of pregnant and postpartum individuals and is associated with complications such as preterm birth, low birth weight, and postpartum depression. Pharmacologic treatment options during pregnancy are limited by concerns about fetal safety.

Methods: A literature review was conducted focusing on studies reporting maternal or neonatal outcomes following prazosin exposure in pregnancy.

Results: One observational study of 11 pregnancies found 54.5% had uneventful outcomes, with rates of preterm birth, miscarriage, and preeclampsia similar to the general population. Hypotension and limited lactation data remain concerns.

Conclusion: Early evidence suggests prazosin may be a relatively safe and …

A New Paliperidone Palmitate Formulation: How Is It Different And Where Does It Fit In Our Array Of Choices For Long-Acting Formulations Of Risperidone And Paliperidone?, Justin Faden, Leslie Citrome

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Long-acting injectable (LAI) antipsychotics have been shown to enhance treatment adherence and outcomes in individuals with schizophrenia, schizoaffective disorder, and bipolar disorder. In recent years, the U.S. Food and Drug Administration (FDA) has approved several LAIs with differing amenities of care, such as mode of administration, duration of oral medication supplementation, dosing frequency, needle gauge and size, and injection volume, amongst others. Additionally, several LAIs are distinct formulations of risperidone and paliperidone, making it difficult to distinguish between formulations, and many providers are unfamiliar with these newer agents. In 2024, a once-monthly LAI formulation of paliperidone palmitate, manufactured by Luye …

Larotrectinib Compared With Real-World Non-Tropomyosin Receptor Kinase Inhibitor Therapies In Patients With Tropomyosin Receptor Kinase Fusion Cancer, Marcia S. Brose, C. Benedikt Westphalen, Xiaoyun Pan, Vadim Bernard-Gauthier, Milena Kurtinecz, Helen Guo, Virginie Aris, Neil R. Brett, Abdelali Majdi, Vivek Subbiah, Nathan A. Pennell, Kenneth L. Kehl, Alexander Drilon

Kimmel Cancer Center Faculty Papers

PURPOSE: Neurotrophic tyrosine receptor kinase gene fusions are oncogenic drivers of various solid tumors. Larotrectinib is a highly selective tropomyosin receptor kinase (TRK) inhibitor approved for patients with TRK fusion cancer on the basis of single-arm trials. This study was a matched comparative effectiveness study of larotrectinib in clinical trials versus standard of care (SOC) in the real-world (RW) setting.

METHODS: Adult patients with advanced/metastatic TRK fusion non-small cell lung cancer, colorectal cancer, soft tissue sarcoma, thyroid cancer, or salivary gland carcinoma were included. Deduplicated data from RW patients were from US and ex-US data sources. Patients in the larotrectinib …

Palovarotene In Fibrodysplasia Ossificans Progressiva: Review And Perspective, Vincent Verheij, Robert Diecidue, Esmée Botman, Joseph Harrington, Nobuhiko Haga, Alberto Hidalgo-Bravo, Patricia Delai, Vrisha Madhuri, Mona Al Mukaddam, Keqin Zhang, Tae-Joon Cho, Rolf Morhart, Richard Keen, Carmen De Cunto, Clive Friedman, Zvi Grunwald, Michael Zasloff, J. Coen Netelenbos, Edward Hsiao, Frederick Kaplan, Robert Pignolo, Christiaan Scott, Elisabeth Marelise Eekhoff

Department of Oral and Maxillofacial Surgery Faculty Papers

INTRODUCTION: Palovarotene is a retinoic acid receptor gamma agonist that was studied in phase-2 and phase-3 clinical trials for the inhibition of new heterotopic ossification (HO) in fibrodysplasia ossificans progressiva (FOP). Despite numerous setbacks and regulatory delays, palovarotene is now the first approved FOP treatment in the U.S.A., Canada and Australia but remains unapproved in Europe where concerns surrounding the drug and its path to regional market authorization persist.

AREAS COVERED: The developmental history of palovarotene and an overview of the clinical trials and the regulatory approval journey are discussed by global FOP experts.

EXPERT OPINION: While post hoc analyses …

Bayesian Population Pharmacokinetic Modeling Of Ondansetron For Neonatal Opioid Withdrawal Syndrome, Kevin Lam, John Mondick, Gary Peltz, Manhong Wu, Walter Kraft

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Ondansetron is an anti-emetic 5-HT3 receptor antagonist being investigated for treating neonatal opioid withdrawal syndrome (NOWS). Sparse PK data were analyzed from a multicenter, double-blind clinical trial with 98 mother/neonate dyads. Pregnant women with opioid use disorder were randomized to receive either placebo or ondansetron 8 mg intravenously within 4 h of delivery. Neonates born to mothers who were randomized to ondansetron received 0.07 mg/kg orally once every 24 h for up to five doses. Using current PK data, model parameters from a two-compartmental structural model from the literature (i.e., a priori model) were updated with the Metropolis-Hastings Markov-chain Monte …

Hyperbaric Oxygen Therapy In The Atls/Acls Resuscitative Management Of Acutely Ill Or Severely Injured Patients With Severe Anemia: A Review, Keith W. Van Meter

School of Medicine Faculty Publications

For short periods, even without the presence of red blood cells, hyperbaric oxygen can safely allow plasma to meet the oxygen delivery requirements of a human at rest. By this means, hyperbaric oxygen, in special instances, may be used as a bridge to lessen blood transfusion requirements. Hyperbaric oxygen, applied intermittently, can readily avert oxygen toxicity while meeting the body's oxygen requirements. In acute injury or illness, accumulated oxygen debt is shadowed by adenosine triphosphate debt. Hyperbaric oxygen efficiently provides superior diffusion distances of oxygen in tissue compared to those provided by breathing normobaric oxygen. Intermittent application of hyperbaric oxygen …

Effects Of Dexmedetomidine As An Adjunct To General Anesthesia On Postoperative Pain And Opioid Consumption In Major Abdominal Surgery, Ahmad H. Elrefahy

Rowan-Virtua Research Day

This review examines the impact of dexmedetomidine, an alpha-2 adrenergic receptor agonist, on postoperative pain and opioid consumption in major abdominal surgery. Dexmedetomidine, known for its sedative, analgesic, and opioid-sparing properties, is increasingly used as an adjunct to anesthesia. Analyzing existing literature, the review found that dexmedetomidine administration alongside general anesthesia significantly improves postoperative pain management and reduces opioid consumption. Patients receiving dexmedetomidine reported decreased postoperative pain ratings and required fewer opioids during the recovery phase. Additionally, intraoperative dexmedetomidine use correlated with reduced postoperative pain severity and increased patient satisfaction compared to control groups. However, potential side effects such as …

Minoxidil Weakens Newly Synthesized Collagen In Fibrotic Synoviocytes From Osteoarthritis Patients, Stefan Sarkovich, Peter P. Issa, Andrew Longanecker, Davis Martin, Kaitlyn Redondo, Patrick Mcternan, Jennifer Simkin, Luis Marrero

School of Medicine Faculty Publications

Purpose: Synovial fibrosis (SFb) formation and turnover attributable to knee osteoarthritis (KOA) can impart painful stiffness and persist following arthroplasty. To supplement joint conditioning aimed at maximizing peri-operative function, we evaluated the antifibrotic effect of Minoxidil (MXD) on formation of pyridinoline (Pyd) cross-links catalyzed by Plod2-encoded lysyl hydroxylase (LH)2b that strengthen newly synthesized type-I collagen (COL1) in fibroblastic synovial cells (FSCs) from KOA patients. MXD was predicted to decrease Pyd without significant alterations to Col1a1 transcription by FSCs stimulated with transforming growth factor (TGF)β1. Methods: Synovium from 10 KOA patients grouped by SFb severity was preserved for picrosirius and LH2b …

Case Series: Continued Remission Of Ptsd Symptoms After Discontinuation Of Prazosin, Christie Richardson, Jonathan Yuh, Jing Su, Martin Forsberg

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Post-traumatic stress disorder is a debilitating chronic illness that affects 6 out of 100 adults after a severe trauma. The alpha-adrenergic antagonist prazosin, which is prescribed off-label for flashbacks and nightmares due to trauma, is often continued indefinitely due to reports of symptoms returning upon discontinuation. There is no standard guidance for a trial of discontinuation of prazosin due to intolerance or side effects. In this case series, three patients are started on prazosin leading to remission of trauma-related symptoms, and symptoms continue to remit after treatment for an average of about 2 years followed by discontinuation of the medication. …

Designing And Synthesizing A Warhead-Fragment Inhibitory Ligand For Ivyp1 Through Fragment-Based Drug Discovery, Samuel Moore

Symposium of Student Scholars

Fragment-based drug discovery (FBDD) is a powerful tool for developing anticancer and antimicrobial agents. Within this, magnetic resonance spectroscopy (NMR) provides a comprehensive qualitative and quantitative approach to screening and validating weak and robust binders with targeted proteins, making NMR among the most attractive strategies in FBDD. Inhibitor of vertebrate lysozyme (Ivyp1) of P. aeruginosa serves as an excellent target because of its active cellular location and implications in clinical prognosis for cystic fibrosis and immunocompromised patients. This study uses current NMR and biophysical techniques to develop a covalent, fragment-linked warhead inhibitor for Ivyp1 through synthetic methods, warhead linking, and …

Design, Synthesis And Development Of Transporter Targeting Agents For Image-Guided Therapy And Drug Delivery, Ning Tsao

Dissertations and Theses (Open Access)

The purpose of this study was to design, synthesize and develop novel transporter targeting agents for image-guided therapy and drug delivery. Two novel agents, N4-guanine (N4amG) and glycopeptide (GP) were synthesized for tumor cell proliferation assessment and cancer theranostic platform, respectively. N4amG and GP were synthesized and radiolabeled with ^99mTc and ⁶⁸Ga. The chemical and radiochemical purities as well as radiochemical stabilities of radiolabeled N4amG and GP were tested. In vitro stability assessment showed both ^99mTc-N4amG and ^99mTc-GP were stable up to 6 hours, whereas ⁶⁸Ga-GP was stable up to 2 hours. Cell culture studies …