Pharmacokinetics of Panaxynol in Mice

Author(s): Hossam Tashkandi, Anusha Chaparala, Sean Peng, Mitzi Nagarkatti, Prakash Nagarkatti, Alexander A. Chumanevich, Lorne J. Hofseth

The purpose of our study is to explore the pharmacokinetic parameters of panaxynol (PA) and understand its potential and dosage used in pre-clinical animal models. For in vitro analysis, 5 μM of PA was added to liver microsomes of mouse and human species. Nicotinamide adenine dinucleotide phosphate was added to initiate enzyme reaction except for the negative control. Liquid chromatography with tandem mass spectrometry (LC-MS/MS) analysis was used to measure concentrations. For in vivo studies, CD-1 mice were treated with PA by intravenous (IV) injection or oral administration (PO). Concentrations of PA were measured in plasma and tissue using LC-MS/MS. Pharmacokinetic parameters were obtained using non-compartmental analysis. Area under the curve concentration versus time was calculated using a linear trapezoidal model. In vitro, PA’s half-life is 21.4 min and 48.1 min in mouse and human liver microsomes, respectively. In vivo, PA has a half-life of 1.5 hr when IV-injected, and 5.9 hr when administered via PO, with a moderate bioavailability of 50.4%. Mice show no signs of toxicity up to 300 mg/kg PO. PA concentrations were highest in colon tissue 2 hr post-treatment at 486 ng/g of colon tissue. PA’s pharmacokinetic properties and low toxicity point to the safety and compatibility of PA with mice.