Absorption and Excretion of Paeoniflorin in Rats

Abstract

The absorption and excretion of paeoniflorin after intravenous and oral administration was studied in rats to evaluate the significance of paeoniflorin in the pharmacological action of Paeony root. The plasma concentration of paeoniflorin after intravenous administration at the doses of 0.5, 2.0 and 5.0 mg kg-1 rapidly decreased, simulated by a biexponential curve, with mean terminal half-lives of 11.0, 9.9 and 12.6 min, respectively. The Vdss values were 0.332, 0. 384 and 0.423 L kg-1 and the CLtot values were 26.1, 31.2 and 30.3 mL min-1 kg-1 at each dose. When given orally at the same doses, the absolute bioavailability values (F) determined by the AUC were 0.032, 0.033 and 0.038, respectively. The cumulative urinary and faecal excretions of paeoniflorin at the dose of 5 mg kg-1 after intravenous administration were 50.5 and 0.22% of the dose within 72 h, and 1.0 and 0.08% of the dose after oral administration within 48 h, respectively. Cumulative biliary excretion after intravenous or oral administration at a dose of 0.5 mg kg-1 was 6.9 and 1.3% of the dose within 24 h, respectively. The total CLR and CLB value after intravenous dosing was less than the CLtot value. These findings suggest that paeoniflorin is metabolized in other organs as well as in the liver. We conclude that paeoniflorin absorbed is excreted mainly in urine, it has a low bioavailability and the metabolites may be involved in the pharmacological action of Paeony root.

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.…”

Bioavailability enhancers of herbal origin: An overview

“…Paeoniflorin is a bioactive monoterpene glucoside, which has been widely used to treat inflammation and arthritic conditions. Paeoniflorin has a poor absorption rate and thus a very low bioavailability (3-4 % ) when administered orally [55] . Co-administration with sinomenine dramatically altered the pharmacokinetic behaviors of paeoniflorin in rats [56] .…”

Pharmacokinetics of Paeoniflorin After Oral Administration of Shao-yao Gan-chao Tang in Mice

“…Recent studies showed that paeoniflorin has a low bioavailability (F) (17,18). The low F value, about 3% (18), may be attributed to the first-pass metabolism in the gut wall or liver, metabolism or decomposition in the intestine by bacterial microflora, and /or poor absorption from gastrointestinal tract (18,19).…”

“…The low F value, about 3% (18), may be attributed to the first-pass metabolism in the gut wall or liver, metabolism or decomposition in the intestine by bacterial microflora, and /or poor absorption from gastrointestinal tract (18,19). To improve the clinical efficacy, therefore, it is important to efficiently increase the F value of paeoniflorin and enhance its concentration in blood.…”

“…To improve the clinical efficacy, therefore, it is important to efficiently increase the F value of paeoniflorin and enhance its concentration in blood. It was suggested that paeoniflorin absorbed is mainly excreted in the urine because approximately 50% of the dose was excreted in urine after intravenous administration (18). A large variability in half-life (t1/2) values was observed, which might be caused by the enterohepatic circulation (18).…”