Absorption, Metabolism, and Excretion of (-)-[2-14C]Epicatechin in Humans
- Conditions
- ADME
- Interventions
- Other: Controlled dietary backgroundOther: (-)-[2-14C]epicatechin intake
- Registration Number
- NCT01969994
- Lead Sponsor
- The Institutes for Pharmaceutical Discovery, LLC
- Brief Summary
The purpose of this study is to determine the absorption, metabolism and excretion of (-)-epicatechin using the radiolabeled tracer (-)-\[2-14C\]epicatechin in healthy male volunteers observing a flavanol-/procyanidin-controlled background diet.
- Detailed Description
Flavanols and their oligomeric derivatives, the procyanidins, are plant-derived compounds commonly present in the human diet. Accumulating data demonstrate a causal role for dietary flavanols in mediating the cardiovascular benefits associated with the consumption of flavanol-/procyanidin-containing foods. In this context, there exists a great interest in understanding the absorption, distribution, metabolism and excretion (ADME) of flavanols in humans. While significant advances in understanding the ADME of flavanols were made, the data obtained thus far remain fairly preliminary and with significant shortfalls and seeming contradictions. Aimed at addressing the challenges and gaps of previous investigations, this study will investigate the ADME of (-)-epicatechin, one of the most abundant dietary flavanols, following the intake of radiolabeled (-)-\[2-14C\]epicatechin by healthy humans observing a flavanol-/procyanidin-controlled background diet.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 12
Not provided
- history or clinical manifestations of significant metabolic, hematological, pulmonary, cardiovascular, gastrointestinal, neurologic, hepatic, renal, urological, or psychiatric disorders;
- allergies to peanuts, nuts, or other foods;
- lactose intolerance;
- history of stomach or intestinal surgery, except that appendectomy or hernia were allowed;
- history of alcoholism or drug addiction within 1 year prior to study entry (ie, at Screening);
- use of any tobacco products (including cigarette, pipe, cigar, chewing, nicotine patch, or nicotine gum) within 6 months prior to study entry;
- use of any agents (excluding those provided as part of this study procedure) affecting the liver enzymes;
- use of aspirin-containing drugs and any other over-the-counter, non-prescription preparations (including vitamins, minerals, and phytotherapeutic/herbal/plant-derived preparations) during the study, unless deemed acceptable by the Investigator;
- use of any alcohol-containing or caffeine-containing products/medications within 72 hours prior to (-)-[2-14C]epicatechin ingestion;
- regular consumption of more than 2 alcoholic drinks per day;
- vegans, vegetarians and/or anyone who consumed less than 1 to 2 servings of fruits and or vegetables per day;
- participation in more than one other radiolabeled investigational study drug trial within 12 months prior to study entry or exposure to significant radiation within 12 months prior to study entry;
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Controlled dietary background & (-)-[2-14C]epicatechin intake (-)-[2-14C]epicatechin intake - Controlled dietary background & (-)-[2-14C]epicatechin intake Controlled dietary background -
- Primary Outcome Measures
Name Time Method Change in levels of (-)-[2-14C]epicatechin-derived radioactivity in blood, plasma, urine, and feces; 0 (prior to the ingestion of (-)-[2-14C]epicatechin), 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours postdose, and at every subsequent 24 hour timepoint up to 240 h or until volunteers meet discharge criteria
- Secondary Outcome Measures
Name Time Method Composite of pharmacokinetic (PK) parameters of total (-)-[2-14C]epicatechin-derived radioactivity levels in plasma, urine and feces. 0 (prior to the ingestion of (-)-[2-14C]epicatechin) up to 240 h or untill volunteers meet discharge criteria PK parameters: Cmax: maximum observed concentration in plasma; tmax: time to maximum concentration in plasma; AUC0-t: area under the plasma radioactivity-time curve from hour 0 to the last measurable concentration in plasma; AUC0-∞: area under the plasma concentration-time curve extrapolated to infinity; λZ: apparent terminal elimination rate constant in plasma; t1/2: apparent terminal elimination half-life in plasma; CL/F: systemic clearance; Vd/F: apparent volume of distribution; CLR: renal clearance; Aeu(0-t): cumulative amount excreted in the urine over each sampling interval and the total interval examined; Aef(0-t): Cumulative amount excreted in the feces over each sampling interval and the total interval examined.
Composite of pharmacokinetic (PK) parameters of individual (-)-[2-14C]epicatechin metabolites in plasma and urine 0 (prior to the ingestion of (-)-[2-14C]epicatechin) up to 240 h or untill volunteers meet discharge criteria PK parameters of each (-)-epicatechin metabolite:
Cmax: maximum observed concentration in plasma; tmax: time to maximum concentration in plasma; AUC0-t: area under the plasma concentration-time curve from hour 0 to the last measurable concentration in plasma; AUC0-∞: area under the plasma concentration-time curve extrapolated to infinity; λZ: apparent terminal elimination rate constant in plasma; t1/2: apparent terminal elimination half-life in plasma; CL/F: systemic clearance; Vd/F apparent volume of distribution; CLR: renal clearance; Aeu(0-t): cumulative amount excreted in the urine over each sampling interval and the total interval examined.
Trial Locations
- Locations (1)
Covance Clinical Pharmacology Inc.
🇺🇸Madison, Wisconsin, United States