title: Pharmacokinetics of centhaquin citrate in a rat model.
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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.affiliation: Department of Pharmacy Practice, Chicago College of Pharmacy, Midwestern University, Downers Grove, IL, USA.|Department of Pharmacy, Northwestern Memorial Hospital, Chicago.
authors.forename: J Nicholas
authors.identifier: http://orcid.org/0000-0001-5184-1385
authors.initials: JN
authors.lastname: O'Donnell
authors.affiliation: Department of Pharmacy Practice, Chicago College of Pharmacy, Midwestern University, Downers Grove, IL, USA.
authors.forename: Anil
authors.initials: A
authors.lastname: Gulati
authors.affiliation: Pharmazz Research Center, Pharmazz India Private Limited, Greater Noida, UP, India.
authors.forename: Manish S
authors.initials: MS
authors.lastname: Lavhale
authors.affiliation: Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), S.A.S. Nagar, Punjab, India.
authors.forename: Shyam S
authors.initials: SS
authors.lastname: Sharma
authors.affiliation: Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), S.A.S. Nagar, Punjab, India.
authors.forename: Arjun J
authors.initials: AJ
authors.lastname: Patel
authors.affiliation: Department of Pharmacy Practice, Chicago College of Pharmacy, Midwestern University, Downers Grove, IL, USA.|Department of Pharmacy, Northwestern Memorial Hospital, Chicago.
authors.forename: Nathaniel J
authors.initials: NJ
authors.lastname: Rhodes
authors.affiliation: Department of Pharmacy Practice, Chicago College of Pharmacy, Midwestern University, Downers Grove, IL, USA.|Department of Pharmacy, Northwestern Memorial Hospital, Chicago.
authors.forename: Marc H
authors.initials: MH
authors.lastname: Scheetz
mesh_terms: D000818:Animals; D002951:Citrates / Q000493:pharmacokinetics*; D006207:Half-Life; D008297:Male; D008954:Models, Biological; D010879:Piperazines / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012771:Shock, Hemorrhagic / Q000378:metabolism
chemical_list: D002951:Citrates; D010879:Piperazines; C045913:centhaquine
keywords: centhaquin citrate; pharmacokinetics; rat