Pharmacokinetics and pharmacodynamics of nitric oxide mimetic agents

Austin Horton; Isaac T Schiefer

doi:10.1016/j.niox.2019.01.001

Pharmacokinetics and pharmacodynamics of nitric oxide mimetic agents

Nitric Oxide. 2019 Mar 1:84:69-78. doi: 10.1016/j.niox.2019.01.001. Epub 2019 Jan 11.

Authors

Austin Horton¹, Isaac T Schiefer²

Affiliations

¹ Department of Medicinal and Biological Chemistry, College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Toledo, USA.
² Department of Medicinal and Biological Chemistry, College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Toledo, USA. Electronic address: Isaac.schiefer@utoledo.edu.

Abstract

Drug discovery focusing on NO mimetics has been hamstrung due to its unconventional nature. Central to these challenges is the fact that direct measurement of molecular NO in biological systems is exceedingly difficulty. Hence, drug development of NO mimetics must rely upon measurement of the NO donating specie (i.e., a prodrug) and a downstream marker of efficacy without directly measuring the molecule, NO, that is responsible for biological effect. The focus of this review is to catalog in vivo attempts to monitor the pharmacokinetics (PK) of the NO donating specie and the pharmacodynamic (PD) readout of NO bioactivity.

Keywords: Furoxan; Nitrates; Nitric oxide; Pharmacokinetics.

Publication types

Research Support, N.I.H., Extramural
Review

MeSH terms

Animals
Drug Development
Drug Liberation
Humans
Nitric Oxide / metabolism*
Nitric Oxide Donors / pharmacokinetics*

Substances

Nitric Oxide Donors
Nitric Oxide

Grants and funding

R01 AG057598/AG/NIA NIH HHS/United States