Pharmacokinetics of isochlorgenic acid C in rats by HPLC-MS: Absolute bioavailability and dose proportionality

Ethnopharmacological relevanceIsochlorgenic acid C (IAC), one of the bioactive compounds of Lonicera japonica, exhibited diverse pharmacological effects. However, its pharmacokinetic properties and bioavailability remained unresolved.Aim of the studyTo determine the absolute bioavailability in rats and the dose proportionality on the pharmacokinetics of single oral dose of IAC.Materials and methodsA validated HPLC-MS method was developed for the determination of IAC in rat plasma. Plasma concentration versus time data were generated following oral and intravenous dosing. The pharmacokinetic analysis was performed using DAS 3.0 software analysis. Absolute bioavailability in rats was determined by comparing pharmacokinetic data after administration of single oral (5, 10 and 25 mg kg−1) and intravenous (5 mg kg−1) doses of IAC. The dose proportionality of AUC(0-∞) and Cmax were analyzed by linear regression.ResultsExperimental data showed that absolute oral bioavailability of IAC in rats across the doses ranged between 14.4% and 16.9%. The regression analysis of AUC(0-∞) and Cmax at the three doses (5, 10 and 25 mg kg−1) indicated that the equations were y=35.23x+117.20 (r=0.998) and y=121.03x+255.74 (r=0.995), respectively.ConclusionsA new HPLC-MS method was developed to determine the bioavailability and the dose proportionality of IAC. Bioavailability of IAC in rats was poor and both Cmax and AUC(0-∞) of IAC had a positive correlation with dose. Evaluation of the pharmacokinetics of IAC will be useful in assessing concentration-effect relationships for the potential therapeutic applications of IAC.

Mean plasma concentration-time profile of IAC after intravenous administration of Isochlorgenic Acid C at the dose of 5 mg·kg-1 and after oral administration at dose of 5, 10 and 25 mg·kg-1, respectively, to rats.Figure optionsDownload high-quality image (88 K)Download as PowerPoint slide