High throughput LC-MS method to investigate postprandial lipemia: Considerations for future precision nutrition research

2021 ◽  
Author(s):  
Justine Marie Mucinski ◽  
Jennifer E Vena ◽  
Maria A Ramos-Roman ◽  
Michael Lassman ◽  
Magdalene Szuszkiewicz-Garcia ◽  
...  
Keyword(s):  
Randomized Study ◽  
Postprandial Lipemia ◽  
Science Research ◽  
Dietary Lipid ◽  
Dietary Lipids ◽  
Isotope Tracer ◽  
Clinical Drug Development ◽  
Nutrition Research ◽  
Appearance Rate ◽  
Clinical Drug

Elevated postprandial lipemia is an independent risk factor for cardiovascular disease, yet methods to quantitate post-meal handling of dietary lipids in humans are limited. This study tested a new method to track dietary lipid appearance using a stable isotope tracer (2H11-oleate) in liquid meals containing three levels of fat (low-LF, 15g; moderate-MF, 30g; high-HF, 60g). Meals were fed to 12 healthy men (mean±SD, age 31.3±9.2y, BMI 24.5±1.9 kg/m2) during four randomized study visits; the HF meal was administered twice for reproducibility. Blood was collected over 8h postprandially, TG-rich lipoproteins (TRL) and particles with a Svedberg flotation rate >400 (Sf>400, n=8) were isolated by ultracentrifugation, and labeling of two TG species (54:3 and 52:2) quantified by LC-MS. Total plasma TRL-TG concentrations were three-fold greater than Sf>400-TG. Both Sf>400- and TRL-TG 54:3 were present at higher concentrations than 52:2 and singly-labeled TG concentrations were higher than doubly-labeled. Further, TG 54:3 and the singly-labeled molecules demonstrated higher plasma absolute entry rates differing significantly across fat levels within a single TG species (P<0.01). Calculation of fractional entry showed no significant differences in label handling supporting the utility of either TG species for appearance rate calculations. These data demonstrate the utility of labeling research meals with stable isotopes to investigate human postprandial lipemia while simultaneously highlighting the importance of examining individual responses. Meal type and timing, control of pre-study activities, and effects of sex on outcomes should match the research goals. The method, optimized here, will be beneficial to conduct basic science research in precision nutrition and clinical drug development.

scholarly journals Has molecular imaging delivered to drug development?

2017 ◽  
Vol 375 (2107) ◽  
pp. 20170112 ◽  
Author(s):  
Philip S. Murphy ◽  
Neel Patel ◽  
Timothy J. McCarthy
Keyword(s):  
Molecular Imaging ◽  
Drug Development ◽  
Clinical Studies ◽  
Pharmaceutical Research ◽  
Whole Body ◽  
Drug Candidate ◽  
Clinical Drug Development ◽  
Target Binding ◽  
The Brain ◽  
Clinical Drug

Pharmaceutical research and development requires a systematic interrogation of a candidate molecule through clinical studies. To ensure resources are spent on only the most promising molecules, early clinical studies must understand fundamental attributes of the drug candidate, including exposure at the target site, target binding and pharmacological response in disease. Molecular imaging has the potential to quantitatively characterize these properties in small, efficient clinical studies. Specific benefits of molecular imaging in this setting (compared to blood and tissue sampling) include non-invasiveness and the ability to survey the whole body temporally. These methods have been adopted primarily for neuroscience drug development, catalysed by the inability to access the brain compartment by other means. If we believe molecular imaging is a technology platform able to underpin clinical drug development, why is it not adopted further to enable earlier decisions? This article considers current drug development needs, progress towards integration of molecular imaging into studies, current impediments and proposed models to broaden use and increase impact. This article is part of the themed issue ‘Challenges for chemistry in molecular imaging’.

Potential of metabolomics in preclinical and clinical drug development

2014 ◽  
Vol 66 (6) ◽  
pp. 956-963 ◽  
Author(s):  
Baldeep Kumar ◽  
Ajay Prakash ◽  
Rakesh Kumar Ruhela ◽  
Bikash Medhi
Keyword(s):  
Drug Development ◽  
Clinical Drug Development ◽  
Clinical Drug

scholarly journals Assessment of cognitive safety in clinical drug development

2016 ◽  
Vol 21 (3) ◽  
pp. 445-453 ◽  
Author(s):  
Jonathan P. Roiser ◽  
Pradeep J. Nathan ◽  
Adrian P. Mander ◽  
Gabriel Adusei ◽  
Kenton H. Zavitz ◽  
...  
Keyword(s):  
Drug Development ◽  
Clinical Drug Development ◽  
Clinical Drug

scholarly journals Clinical Drug Development in Epilepsy Revisited: A Proposal for a New Paradigm Streamlined Using Extrapolation

CNS Drugs ◽  
2016 ◽  
Vol 30 (11) ◽  
pp. 1011-1017 ◽  
Author(s):  
Ian Wadsworth ◽  
Thomas Jaki ◽  
Graeme J. Sills ◽  
Richard Appleton ◽  
J. Helen Cross ◽  
...  
Keyword(s):  
Drug Development ◽  
New Paradigm ◽  
Clinical Drug Development ◽  
Clinical Drug

Framework for the Design of Cannabis-Mediated Phase I Drug-Drug Interaction Studies

2021 ◽  
Vol 16 ◽  
Author(s):  
Diana L. Shuster ◽  
Gina Pastino ◽  
Dirk Cerneus
Keyword(s):  
Drug Interaction ◽  
Drug Development ◽  
The United States ◽  
The Body ◽  
Cannabis User ◽  
Special Population ◽  
Care Providers ◽  
Clinical Drug Development ◽  
Drug Drug Interaction ◽  
Clinical Drug

: Cannabis has become legal in much of the United States similarly to many other countries, for either recreational or medical use. The use of cannabis products is rapidly increasing while the body of knowledge of its myriad of effects still lags. In vitro and clinical data show that cannabis’ main constituents, delta-9-tetrahydrocannabinol and cannabidiol, can affect the pharmacokinetics (PK), safety and pharmacodynamics (PD) of other drugs. Within the context of clinical drug development, the widespread and frequent use of cannabis products has essentially created another special population; that is, the cannabis user. We propose that all clinical drug development programs include a Phase 1 study to assess the drug-drug interaction potential of cannabis as a precipitant on the PK, safety and if applicable, the PD of all new molecular entities (NMEs) in a combination of healthy adult subjects as well as frequent and infrequent cannabis users. This data should be required to inform drug labeling and aid health care providers in treating any patient, as cannabis has quickly become another common concomitant medication and cannabis users, a new special population.

7,8-Dihydroxyflavone and Neuropsychiatric Disorders: A Translational Perspective from the Mechanism to Drug Development

2021 ◽  
Vol 19 ◽  
Author(s):  
Shaojie Yang ◽  
Guoqi Zhu
Keyword(s):  
Drug Development ◽  
Memory Function ◽  
Experimental Studies ◽  
Intestinal Flora ◽  
Neuropsychiatric Disorders ◽  
Tyrosine Kinase Receptor ◽  
Downstream Signaling ◽  
Clinical Drug Development ◽  
Clinical Drug

: 7,8-Dihydroxyflavone (7,8-DHF) is a kind of natural flavonoids, with the potential to cross the blood-brain barrier. 7,8-DHF effectively mimics the effect of brain-derived neurotrophic factor (BDNF) in the brain to selectively activate tyrosine kinase receptor B (TrkB) and downstream signaling pathways, thus playing a neuroprotective role. The preclinical effects of 7,8-DHF have been widely investigated in the neuropsychiatric disorders, including Alzheimer’s disease (AD), Parkinson’s disease (PD), depression and memory impairment. Besides the effect on TrkB, 7,8-DHF could also function through fighting against oxidative stress, cooperating with estrogen receptors or regulating intestinal flora. This review focuses on the recent experimental studies on depression, neurodegenerative diseases and learning and memory function. Additionally, the structural modification and preparation of 7,8-DHF were also concluded and proposed, hoping to provide reference for the follow-up research and clinical drug development of 7,8-DHF in the field of neuropsychiatric disorders.

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