Lipidomics Screening of Celecoxib in ex Vivo Human Whole Blood Assay - Part B
Status:
Completed
Trial end date:
2015-11-01
Target enrollment:
Participant gender:
Summary
Cardiovascular complications of NSAIDs, selective for inhibition of COX-2, stimulated
interest in microsomal prostaglandin E synthase-1 (mPGES-1) as an alternative drug target.
Global deletion of mPGES-1 in mice suppresses prostaglandin (PG) E2 and augments PGI2 by PGH2
substrate rediversion. Unlike COX-2 inhibition or gene deletion, mPGES-1 deletion does not
cause a predisposition to thrombogenesis and hypertension. However, cell-specific deletion of
mPGES-1 reveals that the predominant substrate rediversion product among the prostaglandins
varies by cell type, complicating drug development. The research team has developed an ultra
performance liquid chromatography/ tandem mass spectrometry (UPLC-MS/MS) technique that
allows the quantification of a wide range of lipids beyond the prostaglandin pathway
(leukotrienes, anandamide and the 2-arachidonylglycerol cascades).
This study is designed to examine different pathway interventions from the arachidonic acid
cascade by anti-inflammatory compounds (with a focus on mPGES-1 inhibition) in whole human
blood in vitro (Part A) and ex vivo (Part B). In Part B, healthy volunteers will be asked to
take a single, therapeutic dose of celecoxib and blood and urine samples will be collected
before and after drug administration. Collected blood will be stimulated ex vivo, and lipids
and their metabolites will be measured in blood and urine, respectively. The investigators
expect that lipid profile from ex vivo hWBA done on celecoxib-treated subjects will
recapitulate findings from the in vitro hWBA received with celecoxib-treated human blood
(Part A).