Tashkandi Hossam, Chaparala Anusha, Peng Sean, Nagarkatti Mitzi, Nagarkatti Prakash, Chumanevich Alexander A, Hofseth Lorne J
Drug Discovery and Biomedical Sciences, College of Pharmacy, University of South Carolina, Columbia, SC, USA.
OB/GYN, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
J Cancer Sci Clin Ther. 2020;4(2):133-143. doi: 10.26502/jcsct.5079059. Epub 2020 Jun 1.
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 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 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., PA's half-life is 21.4 min and 48.1 min in mouse and human liver microsomes, respectively. , 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.
我们研究的目的是探索人参炔醇(PA)的药代动力学参数,并了解其在临床前动物模型中的潜在用途和剂量。为了进行分析,将5μM的PA添加到小鼠和人类的肝脏微粒体中。除阴性对照外,添加烟酰胺腺嘌呤二核苷酸磷酸以启动酶反应。采用液相色谱-串联质谱(LC-MS/MS)分析来测量浓度。在研究中,通过静脉注射(IV)或口服给药(PO)对CD-1小鼠进行PA处理。使用LC-MS/MS测量血浆和组织中PA的浓度。使用非房室分析获得药代动力学参数。使用线性梯形模型计算曲线下面积(浓度对时间)。PA在小鼠和人类肝脏微粒体中的半衰期分别为21.4分钟和48.1分钟。静脉注射时,PA的半衰期为1.5小时,口服给药时为5.9小时,生物利用度适中,为50.4%。高达300mg/kg口服给药时,小鼠未表现出毒性迹象。治疗后2小时结肠组织中PA浓度最高,为486ng/g结肠组织。PA的药代动力学特性和低毒性表明PA与小鼠具有安全性和相容性。