Abstract 16607: Human Pharmacokinetics of Centhaquin Citrate, a Novel Resuscitative Agent
Introduction: Centhaquin citrate (PMZ-2010) is a novel agent that has been shown to reduce blood lactate, increase cardiac output and mean arterial pressure, and decrease vascular resistance in hemorrhaged animals. A study (NCT02408731) was conducted to determine the safety, tolerability and pharmacokinetics of PMZ-2010 in healthy human volunteers.
Specific aim: Determine pharmacokinetics of PMZ-2010 in healthy human volunteers.
Methods: A randomized, double-blind, placebo-controlled phase I study was performed at Jehangir Clinical Development Center, Pune, India to determine the pharmacokinetics of PMZ-2010 in healthy male volunteers. Subjects were administered intravenous infusion of PMZ-2010 in doses ranging from 0.005 to 0.10 mg/kg in a volume of 100 ml over 60 min duration. Plasma concentrations of PMZ-2010 were measured at baseline and at 8 points within 8 hours after drug administration. Compartmental models with non-parametric parameter estimation and Bayesian corrections were used for pharmacokinetic model fitting.
Results: The pharmacokinetic parameters of PMZ-2010 were well explained using a two-compartment model. Bayesian predictions for actual concentrations were very good (R2= 0.94) with low bias (-0.112 ng/mL) and imprecision (0.82 ng2 /mL2). Median (CV%) values for elimination coefficient (Ke), volume of distribution (V) and intercompartmental transfer rates (Kcp, Kpc) were 4.1 h-1 (31.7%), 29.5 L (69.8%), 10.4 h-1 (86.3%) and 2.1 h-1 (86.4%), respectively.
Conclusions: The pharmacokinetic parameters of centhaquin citrate in humans are well explained with a two-compartment model. The results of our compartmental analysis are consistent with the results from the previous pharmacokinetic studies in healthy rats and dogs. PMZ-2010 was found to have rapid elimination from plasma.
Author Disclosures: A. Gulati: Ownership Interest; Modest; Issued and pending patents. A.O. Goyal: None. M.S. Lavhale: Employment; Modest; Employed by Patent Licensee. S. Gulati: None. M. Scheetz: None.
- © 2016 by American Heart Association, Inc.