Pharmacokinetics of panaxynol in mice

Abstract

Our research aims to decipher the panaxynol (PA) pharmacokinetic characteristics and gain insight into the drug's use and dosing 
in non-human primate models. Liver microsomes from both mice and humans were treated with 5 M of PA for in vitro testing. 
With the exception of the untreated control, the enzyme reaction was triggered by the addition of nicotinamide adenine 
dinucleotide phosphate. Concentrations were determined using liquid chromatography tandem mass spectrometry (LC- MS/MS) 
analysis. PA was injected intravenously (IV) or orally (PO) into CD-1 mice for in vivo experiments. Using LC-MS/MS, the PA 
levels in plasma and tissue were determined. Non-compartmental analysis was used to determine pharmacokinetic parameters. 
Using a linear trapezoidal model, we determined the area under the concentration versus time curve. The half-lives of PA in mouse 
and human liver microsomes are 21.4 and 48.1 minutes, respectively, when studied in vitro. PA has a moderate bioavailability of 
50.4% in vivo, with a half-life of 1.5 hr after IV-injection and 5.9 hr after PO administration. Evidence from mice suggestsup to 
300 mg/kg orally causes death. Colon tissue concentrations of PA peaked at 486 ng/g 2 hours post-treatment. The minimal toxicity 
and favorable pharmacokinetics of PA suggest that it is well tolerated by mice.