Abstract

Procyanidins are important biologically active compounds, but the pathway and extent of absorption and metabolism are controversial. We conducted a mass balance study to evaluate the total radioactivity excreted in urine and feces after oral administration of [¹⁴C]procyanidin B2 to male rats (n = 5). Urine and feces were collected daily from 0 to 96 h. Absolute bioavailability of ¹⁴C from [¹⁴C]procyanidin B2 was calculated as ∼82% using the values for total urinary ¹⁴C. A pharmacokinetic study measured total radioactivity in the blood (n = 9). Blood samples were collected at designated time intervals (0.5–24 h) after administration. Three treatments were used: 1) intravenous, 2) oral higher dose (21 mg/kg b.wt.), and 3) oral lower dose (10.5 mg/kg). Blood concentration of total ¹⁴C reached a maximum at ∼6 h after ingestion of [¹⁴C]procyanidin B2 (groups II and III), and area under the curve (AUC) was dependent on oral dose. After intravenous or oral administration the terminal half-lives were similar, whereas 8-fold larger values were obtained after oral dosing for total clearance and the apparent volumes of distribution. These pharmacokinetic differences explain the apparently lower ¹⁴C bioavailability (8–11%) for [¹⁴C]procyanidin calculated from blood [AUC_(0–24)] values. After oral administration of [¹⁴C]procyanidin B2, 63% was excreted via urine within 4 days. The data suggest that much of the parent compound administered orally is degraded by the gut microflora before absorption and that these microbial metabolites have a different distribution from the compounds circulating after the intravenous dose.