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Beneficial effects related to the consumption of cocoa and the flavanoid (−)-epicatechin (EPI) have been observed and EPI could be useful for treatment of cardiovascular disease. We studied the pharmacokinetics of pure EPI and assessed the effects of EPI on plasma nitrite healthy volunteers.
50, 100 or 200 mg EPI was administered to 9 volunteers. Vital signs and symptoms were monitored and blood was collected for plasma EPI and metabolites determination. In 4 subjects effects of EPI 50 mg daily for 5 days on plasma nitrite was assessed. EPI and metabolites were measured using liquid chromatography-mass spectroscopy and nitrite using reductive chemiluminescence.
No symptoms or vital sign changes were noted after EPI. Only low levels of plasma EPI were detected. Concentrations of metabolites glucuronidated, sulfated and met-sulfated EPI were 2-40 times that of EPI. Peak plasma concentration and half life for EPI and metabolites were between 1-2 hours over the entire dose range. After 5 days of EPI, plasma nitrite increased by an average of 30%.
EPI was well tolerated in our study with no adverse effects. We demonstrated that EPI is rapidly absorbed and undergoes extensive first pass metabolism. The metabolite to parent compound ratio increased with increasing doses suggesting dose dependent metabolism of EPI. Observed increases plasma nitrite suggest that chronic low dose EPI activates endothelial nitric oxide synthase.
Poster Sessions, Expo North
Monday, March 11, 2013, 9:45 a.m.-10:30 a.m.
Session Title: Pulmonary Hypertension: Pre-Clinical, Clinical, Biomarkers
Abstract Category: 27. Pulmonary Hypertension
Presentation Number: 1294-146
- 2013 American College of Cardiology Foundation