Pharmacokinetics of centhaquin citrate in a dog model.

O'Donnell, J. Nicholas; O'Donnell, E. Paul; Kumar, E. Jeevan; Lavhale, Manish S.; Andurkar, Shridhar V.; Gulati, Anil; Scheetz, Marc H.

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 K e, V c, V p, K cp and K pc 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.

HEMORRHAGIC shock treatment; CARDIOVASCULAR agents; PHARMACOKINETICS; CITRATES; ANIMAL models in research; THERAPEUTICS

Journal of Pharmacy & Pharmacology, 2016, Vol 68, Issue 6, p803

0022-3573

Academic Journal

10.1111/jphp.12554