Abstract
Procyanidins are important biologically-active compounds but the pathway and extent of absorption and metabolism is 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 (U∞). A pharmacokinetic study measured total radioactivity in the blood (n = 9). Blood samples were collected at designated time intervals (0.5 to 24 h) post-administration. Three treatments were used: (I) intravenous, (II) oral higher dose (21 mg.Kg-1 of body weight), and (III) oral lower dose (10.5 mg.Kg-1). Blood concentration of total [14C] reached a maximum at ~6 h after ingestion of [14C]-procyanidin B2 (groups II and III) and AUC was dependent on oral dose. After intravenous or oral administration, the terminal half-lives were similar, while 8-fold larger values were obtained after oral dosing for total clearance (Clp) and the apparent volumes of distribution (Vd). These pharmacokinetic differences explain the apparently lower 14C bioavailability (8-11%) for [14C]-procyanidin calculated from blood (AUC(0-24)) values. Following oral administration of [14C]-procyanidin B2, 63 % was excreted via urine within 4 d. The data suggest that much of the parent compound administered orally is degraded by the gut microflora prior to absorption and that these microbial metabolites have a different distribution from the compounds circulating after the intravenous dose.
Footnotes
- Received September 28, 2009.
- Accepted November 5, 2009.
- The American Society for Pharmacology and Experimental Therapeutics