A5086323589- Pharmacogenetics and Drug Metabolism
- Drug Transport and Resistance Mechanisms
- Drug-Induced Hepatotoxicity and Protection
- HIV/AIDS Research and Interventions
- Biosimilars and Bioanalytical Methods
- HIV/AIDS drug development and treatment
- Gastrointestinal motility and disorders
- Cholinesterase and Neurodegenerative Diseases
- Neuroscience and Music Perception
- Schizophrenia research and treatment
- Pharmacological Effects and Toxicity Studies
- Medication Adherence and Compliance
- Synthesis and biological activity
- HIV Research and Treatment
- Eicosanoids and Hypertension Pharmacology
- Obsessive-Compulsive Spectrum Disorders
- Pharmaceutical studies and practices
- Metabolism and Genetic Disorders
- Calcium signaling and nucleotide metabolism
- Nausea and vomiting management
- HIV, Drug Use, Sexual Risk
- Blood donation and transfusion practices
- Ethics in Clinical Research
- Phosphodiesterase function and regulation
- Digital Mental Health Interventions
Merck & Co., Inc., Rahway, NJ, USA (United States)
2018-2022
University of Tennessee at Knoxville
2020
Eli Lilly (United States)
1993-2008
Washington State University
2000
Novo Nordisk (Denmark)
1997
Oklahoma Foundation for Digestive Research
1997
Walter Reed Army Institute of Research
1988
University of Maryland, Baltimore
1985
Converging lines of evidence implicate the beta-amyloid peptide (Ass) as causative in Alzheimer's disease. We describe a novel class compounds that reduce A beta production by functionally inhibiting gamma-secretase, activity responsible for carboxy-terminal cleavage required production. These molecules are active both 293 HEK cells and neuronal cultures, exert their effect upon without affecting protein secretion, most notably secreted forms amyloid precursor (APP). Oral administration one...
Xanomeline is a novel muscarinic receptor agonist relatively devoid of parasympathomimetic side effects. had high affinity for receptors and much lower variety other neuronal in radioligand binding assays. Functional studies cell lines transfected with the subtypes demonstrated that xanomeline higher potency efficacy m1 m4 than m2, m3, m5 subtypes. Similarly, isolated tissue studies, M1 rabbit vas deferens at M2 guinea pig atria or M3 bladder. Secretion soluble amyloid precursor protein from...
Twelve human and six rhesus monkey liver samples were analyzed in vitro for phase I metabolism II conjugation activity. Of the eight P-450-dependent activities measured, only N-nitrosodimethylamine N-demethylase activity was not significantly different between two species. Coumarin 7-hydroxylase greater as compared with samples, whereas erythromycin N-demethylase, benzphetamine pentoxyresorufin O-dealkylase, ethoxycoumarin O-deethylase, ethoxyresorufin O-deethylase microsome (p < or = 0.01)....
Dried blood spot (DBS) sample collection has gained increased interest across the pharmaceutical industry as a potential alternative to plasma for pharmacokinetic (PK) evaluations. However, regulatory guidelines and examples of late-stage clinical trial applications in literature are lacking. This paper communicates Merck's strategy implementation DBS exemplified by experience on program (MK-8931). In this program, was proposed sole matrix phase 3 studies decrease logistical burden an aging...
Machine learning-based facial and vocal measurements have demonstrated relationships with schizophrenia diagnosis severity. Demonstrating utility validity of remote automated assessments conducted outside controlled experimental or clinical settings can facilitate scaling such measurement tools to aid in risk assessment tracking treatment response populations that are difficult engage.This study aimed determine the accuracy machine acquired through remotely smartphones.Measurements...
A series of vinylacetylene analogs Enviroxime (1) was synthesized. The new compounds are potent inhibitors poliovirus in tissue culture. Cross-sensitivity with Enviroxime-derived mutants shows that the have same mechanism action as Enviroxime, which involves viral 3A protein. In studies Rhesus monkeys, p-fluoro derivative 12 found to be unique providing oral bioavailability. Metabolism using hepatic microsomes suggest this procedure would a useful vitro method for selecting appropriate...
Frequent viral load testing is necessary during analytical treatment interruptions (ATIs) in HIV cure-directed clinical trials, though such may be burdensome and inconvenient to trial participants. We implemented a national, cross-sectional survey the United States examine acceptability of novel home-based peripheral blood collection device for testing. Between June August 2021, we distributed an online people with (PWH) community members, biomedical cure researchers care providers....
Merck & Co, Inc (Kenilworth, NJ) is investing in approaches to enrich clinical trial data and augment decision making through use of digital health technologies, outpatient sampling, real‐time access. As part this strategy, a phase I study was conducted explore few technologies interest. In fixed‐sequence two‐period trial, 16 healthy subjects were administered 50‐mg once‐daily sitagliptin packaged bottle that electronically captured the date time medication dispensed (period 1)...
Irritable bowel syndrome (IBS) is a pathopysiolocal condition characterized by abnormal habits that are frequently accompanied abdominal pain. Current therapy based on reducing high-amplitude GI contractions with nonselective muscarinic antagonists limited in efficacy due to typical side effects and provides no pain relief. We have previously found potent antinociceptive agents acting through receptors. In the present work, new 1,2,5-thiadiazole-based structures activity been evaluated both...
People with HIV (PWH) and community members have advocated for the development of a home-based viral load test device that could make analytical treatment interruptions (ATIs) less burdensome.
Abstract Background Machine learning-based facial and vocal measurements have demonstrated relationships with schizophrenia diagnosis severity. Here, we determine their accuracy of when acquired through automated assessments conducted remotely smartphones. Demonstrating utility validity remote outside controlled experimental settings can facilitate scaling such measurement tools to aid in risk assessment tracking treatment response difficult engage populations. Methods Measurements...
The metabolism and disposition of moxonidine (4-chloro-5-(imidazolidin-2-ylidenimino)-6-methoxy-2-methylp yrimidine ), a potent central-acting antihypertensive agent, were investigated in F344 rats. After an i.v. or oral administration 0.3 mg/kg [(14)C]moxonidine, the maximum plasma concentrations determined to be 146.0 4.0 ng/ml, respectively, elimination half-lives 0.9 1.1 h, respectively. bioavailability was 5.1%. metabolic profiles after 5 [(14)C]moxonidine. More than fifteen phase I II...
The metabolism and pharmacokinetics of moxonidine, a potent central-acting antihypertensive agent, were studied in four healthy subjects after single oral administration approximately 1 mg (approximately 60 muCi) [(14)C(3)]moxonidine. Moxonidine was rapidly absorbed, with peak plasma concentration achieved between 0.5 to 2 h postdose. maximal the area under curve unchanged moxonidine are lower than those determined for radioactivity, indicating presence circulating metabolite(s). total...
Lisa Shipley is Vice President of Pharmacokinetics, Pharmacodynamics and Drug Metabolism at Merck Research Laboratories. She responsible for preclinical clinical ADME activities molecular biomarker assay development all research sites support programs from discovery through to post-product launch. Prior joining in 2008, spent over 20 years Eli Lilly Company roles increasing responsibility, including the positions executive director Lean Six Sigma vice president Disposition, PK/PD Trial...