Pharmacokinetics of novel antimicrobial cationic peptides NAB 7061 and NAB 739 in rats following intravenous administration
FEA Ali, G Cao, A Poudyal, T Vaara… - Journal of …, 2009 - academic.oup.com
Journal of antimicrobial chemotherapy, 2009•academic.oup.com
Objectives 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 …
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 …
Objectives
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.
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