The Pharmacokinetics and Tissue Distributions of Nine Steroidal Saponins from Paris polyphylla in Rats.

BACKGROUND AND OBJECTIVES Paris polyphylla (P. polyphylla) is a herb widely used in traditional Chinese medicine to treat various diseases. This study used ultrahigh-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) to study the pharmacokinetics and tissue distributions of nine steroidal saponins from P. polyphylla. METHODS P. polyphylla extract was administered to rats intravenously (i.v.) and orally (p.o.). The concentrations of the nine main bioactive components of the extract were determined in plasma and tissue samples using UPLC-MS/MS. The nine saponin compounds were also incubated in an anaerobic environment with intestinal flora suspension solution to investigate hydrolysis by intestinal flora. RESULTS After oral administration of the P. polyphylla extract, polyphyllin VII was found to have the highest maximum concentration (Cmax, 17.0 ± 2.24 µg/L) of all nine components, followed by the Cmax values of dioscin (16.17 ± 0.64 µg/L) and polyphyllin H (11.75 ± 1.28 µg/L), while the Cmax values of polyphyllin I, polyphyllin II, progenin III, polyphyllin IV, gracillin, and polyphyllin were less than 10 µg/L. The bioavailabilities of all nine components were less than 1%. All the compounds were hydrolyzed by intestinal flora and were predominantly distributed in the liver and lungs. CONCLUSIONS The nine compounds presented different pharmacokinetic parameter values, and multiple administrations did not accumulate in the body. The bioavailabilities of the compounds were low, partly because of hydrolysis by intestinal flora. The nine compounds were mainly distributed in the liver and lungs, which may be target organs.