Simultaneous Characterization of Intravenous and Oral Pharmacokinetics of Lychnopholide in Rats by Transit Compartment Model

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.

Rapid and efficient method for the quantification of lychnopholide in rat plasma by liquid chromatography–tandem mass spectrometry for pharmacokinetic application

“…To our knowledge, this is the first time an LC‐MS/MS method was developed to quantify LYC in the plasma. The method presented here is suitable for pharmacokinetics studies and allowed us to determine the noncompartmental and compartmental pharmacokinetc parameters of LYC by simultaneously modelling the concentration–time profiles after both oral and intravenous administrations of LYC (Lachi‐Silva et al ., ).…”

“…In the same study, the protein binding was determined as ~99% in rat total plasma for three different concentrations of LYC (Lachi‐Silva et al ., ). The high protein binding of LYC is probably the cause for the low average recovery rate, as the liquid–liquid extraction may not have extracted the compound thoroughly in the sample.…”

Efficacy of Lychnopholide Polymeric Nanocapsules after Oral and Intravenous Administration in Murine Experimental Chagas Disease

“…A recent study with rats suggested the favorable use of oral LYC as an active substance or pharmacological agent because of its physicochemical properties of good permeability and rapid absorption, distribution, and elimination, resulting in 68% oral bioavailability (21). However, LYC has poor solubility, and its fast elimination implies its possible administration in repeated doses.…”

“…Recently, it was reported that LYC administered orally to rats showed suitable pharmacokinetic characteristics (21). Oral administration is the preferred route for the treatment of parasitic diseases, including CD.…”

Increased Body Exposure to New Anti-Trypanosomal Through Nanoencapsulation

“…12% in PBS/Tween 8 ), probably because proteins act as LYC acceptors favouring LYC partition to the external aqueous medium from the triglyceride-based core of the NC. The main driving force is probably the LYC strong binding to mouse plasma proteins as recently reported with rat plasma 25 . This accelerating effect of plasma proteins on the release of a lipophilic drug has already been observed with similar PLA-PEG NC 26 , 27 .…”