O'Donnell J Nicholas, Gulati Anil, Lavhale Manish S, Sharma Shyam S, Patel Arjun J, Rhodes Nathaniel J, Scheetz Marc H
Department of Pharmacy Practice, Chicago College of Pharmacy, Midwestern University, Downers Grove, IL, USA.
Department of Pharmacy, Northwestern Memorial Hospital, Chicago.
J Pharm Pharmacol. 2016 Jan;68(1):56-62. doi: 10.1111/jphp.12498. Epub 2016 Jan 4.
Centhaquin citrate is a novel agent being developed for use in the treatment of haemorrhagic shock. It has decreased mortality in rat, rabbit and pig models of hypovolaemic shock compared to hypertonic saline and lactated Ringer's resuscitation. The pharmacokinetics of centhaquin citrate have not been described to date.
Sixteen male Sprague Dawley rats were given an intravenous bolus of 0.45 mg/kg centhaquin citrate. Rats were divided into two groups; plasma concentrations were measured at five time points for each group within 24 h after administration. Competing compartmental pharmacokinetic models were assessed. The nonparametric adaptive grid function within the Pmetrics package for R was used for parameter estimation. Predicted concentrations were calculated using population median and individual Bayesian posterior parameters.
A two-compartment model of centhaquin citrate best fit the data. Median (IQR) values for elimination coefficient (Ke), volume of distribution (V) and intercompartmental transfer rates (Kcp, Kpc) were 8.8 (5.2-12.8) h(-1), 6.4 (2.8-10.4) l, 11.9 (4.6-15.0) h(-1) and 3.7 (2.3-9.1) h(-1), respectively.
This is the first report of the pharmacokinetic parameters of centhaquin citrate in a rat model. Centhaquin citrate was found to have a short half-life with a large volume of distribution.
柠檬酸辛喹铵是一种正在研发用于治疗失血性休克的新型药物。与高渗盐水和乳酸林格氏液复苏相比，它在低血容量休克的大鼠、兔和猪模型中降低了死亡率。迄今为止，尚未对柠檬酸辛喹铵的药代动力学进行描述。
给16只雄性Sprague Dawley大鼠静脉推注0.45mg/kg柠檬酸辛喹铵。将大鼠分为两组；给药后24小时内每组在五个时间点测量血浆浓度。评估竞争性房室药代动力学模型。使用R语言的Pmetrics包中的非参数自适应网格函数进行参数估计。使用总体中位数和个体贝叶斯后验参数计算预测浓度。
柠檬酸辛喹铵的二室模型最符合数据。消除系数（Ke）、分布容积（V）和房室间转运速率（Kcp、Kpc）的中位数（IQR）值分别为8.8（5.2 - 12.8）h⁻¹、6.4（2.8 - 10.4）l、11.9（4.6 - 15.0）h⁻¹和3.7（2.3 - 9.1）h⁻¹。
这是关于柠檬酸辛喹铵在大鼠模型中药代动力学参数的首次报告。发现柠檬酸辛喹铵半衰期短，分布容积大。
