J Nicholas O'Donnell1,2, Anil Gulati1, Manish S Lavhale3, Shyam S Sharma4, Arjun J Patel4, Nathaniel J Rhodes1,2, Marc H Scheetz1,2. 1. Department of Pharmacy Practice, Chicago College of Pharmacy, Midwestern University, Downers Grove, IL, USA. 2. Department of Pharmacy, Northwestern Memorial Hospital, Chicago. 3. Pharmazz Research Center, Pharmazz India Private Limited, Greater Noida, UP, India. 4. Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), S.A.S. Nagar, Punjab, India.
Abstract
OBJECTIVE: 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. METHODS: 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. KEY FINDINGS: 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. CONCLUSION: 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.
OBJECTIVE: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. METHODS: 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. KEY FINDINGS: 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. CONCLUSION: 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.
Authors: Nathaniel J Rhodes; Walter C Prozialeck; Thomas P Lodise; Natarajan Venkatesan; J Nicholas O'Donnell; Gwendolyn Pais; Cameron Cluff; Peter C Lamar; Michael N Neely; Anil Gulati; Marc H Scheetz Journal: Antimicrob Agents Chemother Date: 2016-09-23 Impact factor: 5.191
Authors: M D Joshi; J N O'Donnell; N Venkatesan; J Chang; H Nguyen; N J Rhodes; G Pais; R L Chapman; B Griffin; M H Scheetz Journal: Clin Transl Sci Date: 2017-07-04 Impact factor: 4.689