In-vivo Assessment of Extrahepatic Metabolism of Paeoniflorin in Rats: Relevance to Intestinal Floral Metabolism

Abstract

The extraction ratios of paeoniflorin in gut wall (EG), liver (EH) and lung (EL) were assessed by comparing AUCs after various routes of its administration to estimate the first-pass effects and the metabolism by intestinal flora. Pulmonary extraction ratio of paeniflorin was assessed by comparing AUCs calculated from venous and arterial plasma concentrations after its intravenous administration (0.5 mg kg-1). The mean pulmonary extraction ratio was estimated to be 0.06. The hepatic extraction ratio (EH was assessed by comparing AUCs after intraportal and intravenous administrations (0.5 and 5 mg kg-1). The plasma concentration profiles of paeoniflorin after intraportal administration were very close to those after intravenous administration, suggesting a negligible hepatic extraction ratio of paeoniflorin. The AUC value after intraperitoneal administration (0.5 mg kg-1) was greater than that after intraportal or intravenous administration. This finding suggests that paeoniflorin is not metabolized in the gut wall. The transference of paeoniflorin from the serosal side to the mucosal side was evaluated by the in-vitro everted sac method. The low intestinal permeability (19.4% at 60 min) was demonstrated by the comparison with phenobarbital (63.1% at 60 min). We conclude that paeoniflorin is not metabolize by gut wall, liver and lung, its poor absorption from the intestine results in extremely low bioavailability and the unabsorbed fraction of paeoniflorin is degraded by the intestinal flora.

Mechanisms Responsible for Poor Oral Bioavailability of Paeoniflorin: Role of Intestinal Disposition and Interactions with Sinomenine

“…Previous studies had reported low bioavailability of orally administered paeoniflorin in rats (approximately 3 Y 4%) (3,4), and our own pharmacokinetic study was consistent with this observation (5). An earlier study indicated that higher plasma concentrations of paeoniflorin were achieved by using a more crude extract of the plant (6).…”

Influence of co-administrated sinomenine on pharmacokinetic fate of paeoniflorin in unrestrained conscious rats

“…However, previous pharmacokinetic studies have shown that paeoniflorin has a poor absorption rate, and thus a very low bioavailability (3-4%) when adminis-tered orally. This is probably due to limited transportation of paeoniflorin across the gastrointestinal mucosa (Takeda et al, 1995(Takeda et al, , 1997. In Mainland China, the total glucosides of Paeonia lactiflora Pall.…”

Metabolism of Constituents in Huangqin-Tang, a Prescription in Traditional Chinese Medicine, by Human Intestinal Flora

“…[8][9][10][11][12][13][14] They were converted into the metabolites baicalein (B), paeonimetabolins (PM) and glycyrrhetinic acid (GA) by HIF in vitro, which were absorbed into body. [15][16][17][18][19][20][21][22][23] In our previous paper, 24) we established the method to simultaneously analyze the 14 chemical constituents of Huangqin-Tang by HPLC. Among these compounds, there are several pairs of original compounds and metabolites.…”