title: Pharmacokinetics of novel antimicrobial cationic peptides NAB 7061 and NAB 739 in rats following intravenous administration.
abstract: OBJECTIVE
  To determine the disposition of novel antimicrobial cationic peptides NAB 7061 and NAB 739 following intravenous administration in rats.
  
  
  METHODS
  Sprague-Dawley rats received a single intravenous bolus of 1.0 mg/kg NAB 7061 or NAB 739. Plasma concentrations of NAB 7061 or NAB 739 were determined by HPLC or liquid chromatography-mass spectrometry. The pharmacokinetic parameters of NAB 7061 and NAB 739 were calculated using non-compartmental analysis.
  
  
  RESULTS
  Corresponding total body clearance, volume of distribution at steady state and terminal half-life of NAB 7061 and NAB 739 averaged 3.84 and 2.63 mL/min/kg, 339 and 222 mL/kg, and 66.2 and 69.0 min, respectively. Approximately 7.16% and 19.4% of the dose was eliminated in an unchanged form via the urine in 24 h for NAB 7061 and NAB 739, respectively.
  
  
  CONCLUSIONS
  While both compounds had generally similar pharmacokinetics to colistin, even minor alterations in the chemical structures appear to have an impact on their pharmacokinetics, especially on their clearance by the kidney. There are also substantial differences in relation to the relative contributions of renal and non-renal clearance to overall elimination from the body.
authors.affiliation: Facility for Anti-infective Drug Development and Innovation, Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, Victoria, Australia.
authors.forename: Feda' Emad Atta
authors.initials: FE
authors.lastname: Ali
authors.forename: Guoying
authors.initials: G
authors.lastname: Cao
authors.forename: Anima
authors.initials: A
authors.lastname: Poudyal
authors.forename: Timo
authors.initials: T
authors.lastname: Vaara
authors.forename: Roger L
authors.initials: RL
authors.lastname: Nation
authors.forename: Martti
authors.initials: M
authors.lastname: Vaara
authors.forename: Jian
authors.initials: J
authors.lastname: Li
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D002853:Chromatography, Liquid; D003091:Colistin / Q000493:pharmacokinetics; D007275:Injections, Intravenous; D013058:Mass Spectrometry; D008657:Metabolic Clearance Rate; D010949:Plasma / Q000737:chemistry; D011113:Polymyxins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D023181:Antimicrobial Cationic Peptides; C546018:NAB 7061 peptide; C546019:NAB 739 peptide; D011113:Polymyxins; D003091:Colistin