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DOI: 10.1055/s-0035-1546214
Simultaneous Characterization of Intravenous and Oral Pharmacokinetics of Lychnopholide in Rats by Transit Compartment Model[*]
Publication History
received 11 March 2015
revised 19 May 2015
accepted 25 May 2015
Publication Date:
28 July 2015 (online)
![](https://www.thieme-connect.de/media/plantamedica/20151213/lookinside/thumbnails/10-1055-s-0035-1546214_pmz0261-1.jpg)
Abstract
The pharmacokinetic properties of a new molecular entity are important aspects in evaluating the viability of the compound as a pharmacological agent. The sesquiterpene lactone lychnopholide exhibits important biological activities. The objective of this study was to characterize the pharmacokinetics of lychnopholide after intravenous administration of 1.65 mg/kg (n = 5) and oral administration of 3.3 mg/kg (n = 3) lychnopholide in rats (0.2 ± 0.02 kg in weight) through nonlinear mixed effects modeling and non-compartmental pharmacokinetic analysis. A highly sensitive analytical method was used to quantify the plasma lychnopholide concentrations in rats. Plasma protein binding of this compound was over 99 % as determined by a filtration method. A two-compartment body model plus three transit compartments to characterize the absorption process best described the disposition of lychnopholide after both routes of administration. The oral bioavailability was approximately 68 %. The clearance was 0.131 l/min and intercompartmental clearance was 0.171 l/min; steady-state volume of distribution was 4.83 l. The mean transit time for the absorption process was 9.15 minutes. No flip-flop phenomenon was observed after oral administration. The pharmacokinetic properties are favorable for further development of lychnopholide as a potential oral pharmacological agent.
Key words
lychnopholide - pharmacokinetic - transit compartment - model-based development - pharmacognosy - population pharmacokinetic* Dedicated to Professor Dr. Dr. h. c. mult. Adolf Nahrstedt on the occasion of his 75th birthday.
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