Pharmacokinetics of centhaquin citrate in a dog model.
OBJECTIVE
Centhaquin citrate is a novel agent that is being developed for use in the resuscitation of patients with haemorrhagic shock. While pharmacokinetics have been described in small animal models, the pharmacokinetic parameters of centhaquin citrate in large mammals have yet to be described.


METHODS
Four healthy Beagle dogs (two males and two females) were given an intravenous bolus of 1.0 mg/kg centhaquin citrate. Plasma concentrations were measured at baseline and at ten time points within 24 h after administration. Multiple compartmental models were built and compared. The nonparametric adaptive grid function within the Pmetrics package for R was used for parameter estimation. Predicted concentrations were calculated using population mean and individual Bayesian posterior parameters.


RESULTS
Centhaquin citrate pharmacokinetic parameters were best described using a two-compartment model. Median (IQR) values for Ke , Vc , Vp , Kcp and Kpc were 4.9 (4.4-5.2) h(-1) , 328.4 (304.0-331.9) l, 1000.6 (912.3-1042.4) l, 10.6 (10.3-11.1) h(-1) and 3.2 (2.9-3.7) h(-1) , respectively.


CONCLUSIONS
Pharmacokinetic parameters of centhaquin citrate in a large mammal have been described. A large volume of distribution and rapid elimination were observed, consistent with previous work in rats.
Department of Pharmacy Practice, Chicago College of Pharmacy, Midwestern University, Downers Grove, IL, USA.|Department of Pharmacy, Northwestern Memorial Hospital, Chicago, IL, USA.
J Nicholas
http://orcid.org/0000-0001-5184-1385
JN
O'Donnell
Department of Pharmacy Practice, Chicago College of Pharmacy, Midwestern University, Downers Grove, IL, USA.|Department of Pharmacy, Rush University Medical Center, Chicago, IL, USA.
E Paul
EP
O'Donnell
Pharmazz Research Center, Pharmazz India Private Limited, Greater Noida, India.
E Jeevan
EJ
Kumar
Pharmazz Research Center, Pharmazz India Private Limited, Greater Noida, India.
Manish S
MS
Lavhale
Department of Pharmaceutical Sciences, Chicago College of Pharmacy, Midwestern University, Downers Grove, IL, USA.
Shridhar V
SV
Andurkar
Department of Pharmaceutical Sciences, Chicago College of Pharmacy, Midwestern University, Downers Grove, IL, USA.
Anil
A
Gulati
Department of Pharmacy Practice, Chicago College of Pharmacy, Midwestern University, Downers Grove, IL, USA.|Department of Pharmacy, Northwestern Memorial Hospital, Chicago, IL, USA.
Marc H
MH
Scheetz
D000818:Animals; D001499:Bayes Theorem; D004285:Dogs; D005260:Female; D007275:Injections, Intravenous; D008297:Male; D023421:Models, Animal; D008954:Models, Biological; D010879:Piperazines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
D010879:Piperazines; C045913:centhaquine
centhaquin citrate; dog; pharmacokinetics