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JAC Advance Access originally published online on September 10, 2009
Journal of Antimicrobial Chemotherapy 2009 64(5):1067-1070; doi:10.1093/jac/dkp331
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© The Author 2009. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Original research

Pharmacokinetics of novel antimicrobial cationic peptides NAB 7061 and NAB 739 in rats following intravenous administration

Feda' Emad Atta Ali1,{dagger}, Guoying Cao1,2,{dagger}, Anima Poudyal1, Timo Vaara3, Roger L. Nation1,{ddagger}, Martti Vaara3,4 and Jian Li1,*,{ddagger}

1 Facility for Anti-infective Drug Development and Innovation, Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, Victoria, Australia 2 Department of Pharmacy, Beijing Hospital, Beijing 100730, P. R. China 3 Northern Antibiotics Ltd, FI-00720 Helsinki, Finland 4 Division of Clinical Microbiology, Helsinki University Hospital, FI-00029 HUSLAB, Helsinki, Finland

Received 23 April 2009; returned 22 June 2009; revised 4 August 2009; accepted 17 August 2009

* Corresponding author. Tel: +61-3-9903-9702; Fax: +61-3-9903-9629; E-mail: Jian.Li{at}pharm.monash.edu.au

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.

Keywords: polymyxin , new antibiotics , PK

{dagger} Both authors made an equal contribution.

{ddagger} Joint senior authors.


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