J Nicholas O'Donnell1,2, E Paul O'Donnell1,3, E Jeevan Kumar4, Manish S Lavhale4, Shridhar V Andurkar5, Anil Gulati5, 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, IL, USA. 3. Department of Pharmacy, Rush University Medical Center, Chicago, IL, USA. 4. Pharmazz Research Center, Pharmazz India Private Limited, Greater Noida, India. 5. Department of Pharmaceutical Sciences, Chicago College of Pharmacy, Midwestern University, Downers Grove, IL, USA.
Abstract
OBJECTIVES: 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. KEY FINDINGS: 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.
OBJECTIVES: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. KEY FINDINGS: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.
Authors: Sean N Avedissian; Gwendolyn Pais; Jiajun Liu; J Nicholas O'Donnell; Thomas P Lodise; Michael Neely; Walter C Prozialeck; Peter C Lamar; Leighton Becher; Marc H Scheetz Journal: Antimicrob Agents Chemother Date: 2021-02-17 Impact factor: 5.191
Authors: Sean N Avedissian; Gwendolyn M Pais; J Nicholas O'Donnell; Thomas P Lodise; Jiajun Liu; Walter C Prozialeck; Medha D Joshi; Peter C Lamar; Leighton Becher; Anil Gulati; William Hope; Marc H Scheetz Journal: J Antimicrob Chemother Date: 2019-08-01 Impact factor: 5.790