Abstract

(Pharmacokinetics and Bioanalysis Core) The Pharmacokinetics and Bioanalysis core will support both the preclinical and clinical studies. It will conduct the pharmacokinetic analyses of insulin in plasma, cerebrospinal (CSF) and brain tissue in the EcoHIV mouse model. It will also determine levels of antiretroviral (ARV) drugs and glucose levels in plasma, CSF, and brain tissue. In conjunction with the pharmacological results obtained in the EcoHIV model, the core will establish a pharmacokinetic/pharmacodynamic (PK/PD) model relating drug exposures to positive efficacy endpoints. Results from the mouse model will also inform on potential side effects of insulin brain exposure, interaction between insulin and ARV administration, and aide in the choice of CSF markers to follow insulin efficacy in humans. The core will support the clinical studies with bioanalyses of insulin and glucose in CSF and plasma as well as evaluate ARV drugs in plasma from clinical studies to ensure insulin does not alter ARV disposition. Core scientists have extensive experience with pharmacokinetics and bioanalysis including the specific measurements mentioned above.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Program Projects (P01)
Project #
1P01MH105280-01A1
Application #
8993566
Study Section
Special Emphasis Panel (ZMH1-ERB-M (03))
Project Start
Project End
Budget Start
2015-09-01
Budget End
2016-05-31
Support Year
1
Fiscal Year
2015
Total Cost
$111,012
Indirect Cost
$42,486

  Institution

Name
Johns Hopkins University
Department
Type
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21205

  Publications

Chan, Parco; Saleem, Mahwesh; Herrmann, Nathan et al. (2018) Ceramide Accumulation Is Associated with Declining Verbal Memory in Coronary Artery Disease Patients: An Observational Study. J Alzheimers Dis 64:1235-1246
Nedelcovych, Michael T; Gadiano, Alexandra J; Wu, Ying et al. (2018) Pharmacokinetics of Intranasal versus Subcutaneous Insulin in the Mouse. ACS Chem Neurosci 9:809-816
Chaudhuri, Amrita Datta; Dastgheyb, Raha M; Yoo, Seung-Wan et al. (2018) TNF? and IL-1? modify the miRNA cargo of astrocyte shed extracellular vesicles to regulate neurotrophic signaling in neurons. Cell Death Dis 9:363
Nedelcovych, Michael T; Manning, Arena A; Semenova, Svetlana et al. (2017) The Psychiatric Impact of HIV. ACS Chem Neurosci 8:1432-1434
Ubaida-Mohien, Ceereena; Lamberty, Benjamin; Dickens, Alex M et al. (2017) Modifications in acute phase and complement systems predict shifts in cognitive status of HIV-infected patients. AIDS 31:1365-1378
Nedelcovych, Michael T; Tenora, Lukáš; Kim, Boe-Hyun et al. (2017) N-(Pivaloyloxy)alkoxy-carbonyl Prodrugs of the Glutamine Antagonist 6-Diazo-5-oxo-l-norleucine (DON) as a Potential Treatment for HIV Associated Neurocognitive Disorders. J Med Chem 60:7186-7198
Nedelcovych, Michael; Dash, Ranjeet P; Tenora, Lukáš et al. (2017) Enhanced Brain Delivery of 2-(Phosphonomethyl)pentanedioic Acid Following Intranasal Administration of Its ?-Substituted Ester Prodrugs. Mol Pharm 14:3248-3257
Saleem, Mahwesh; Herrmann, Nathan; Dinoff, Adam et al. (2017) A Lipidomics Approach to Assess the Association Between Plasma Sphingolipids and Verbal Memory Performance in Coronary Artery Disease Patients Undertaking Cardiac Rehabilitation: A C18:0 Signature for Cognitive Response to Exercise. J Alzheimers Dis 60:829-841
Ubaida-Mohien, Ceereena; Lamberty, Benjamin; Dickens, Alex M et al. (2017) Informatic interrogation of CSF proteomic profiles from HIV-infected subjects implicates acute phase and complement systems in shifting cognitive status. AIDS :
Saylor, Deanna; Dickens, Alex M; Sacktor, Ned et al. (2016) HIV-associated neurocognitive disorder - pathogenesis and prospects for treatment. Nat Rev Neurol 12:309

Showing the most recent 10 out of 18 publications