Pharmacokinetics of Valerenic Acid in Rats after Intravenous and Oral Administrations.

Valerenic acid (VA), a sesquiterpenoid, is one of the major secondary bioactive metabolites of Valeriana officinalis L. Until now in vivo studies on the absorption, bioavailability, disposition, and metabolism of VA are limited. We established and validated an LC-MS/MS assay for the determination of VA in rat plasma and successfully used this method for pharmacokinetic studies in rats after intravenous (i.v.) and oral administrations. The plasma concentration-time data was analyzed by both non-compartmental and compartmental approaches using Win Nonlin software. Following i.v. administration, the disposition of VA in rat plasma was biphasic, subdivided into a fast distribution and a slow elimination phase. The half-life of the distribution phase was 6-12min, and that of the terminal elimination phase 6-46 h, indicating a possible large tissue binding. Disposition PK of valerenic acid after oral treatment was also described by a two-compartment model with a clearance (CL/F) of 2-5L ⋅ h ⋅ kg-1 and volume of distribution of (Vd) 17-20 L ⋅ kg-1. The extent of absorption (F) after oral administration was estimated to be 33.70% with a half-life of 2.7-5 h. Dose proportionality was observed in terms of dose and AUCs, suggesting linear pharmacokinetics at the dose levels studied in rats. [ABSTRACT FROM AUTHOR]