The pharmacokinetic studies, performed in Sprague-Dawley rats, showed that the serum half-lives of NAB739 and NAB7061 were close to that of colistin. However, both NAB compounds had much greater renal clearance and much higher urinary recovery than observed for colistin. Accordingly, and in contrast to colistin and polymyxin B, the NAB compounds are excreted into urine to a significant extent. This indicates that the reuptake of the NAB compounds in the proximal tubuli of the kidneys is less intense than that of colistin and polymyxin B.
The extensive reuptake is regarded to be the mechanism of the nephrotoxicity of polymyxins. Thus the reported findings suggest that NAB739 and NAB7061 are less nephrotoxic than colistin and polymyxin B. They are also in line with the previous finding (Vaara M. et al., 2008) that the affinities of NAB739 and NAB7061 for isolated rat kidney brush border membrane are significantly lower than that of polymyxin B.
These two studies were presented in the Poster Session #290 on Tuesday, October 28, 2008, 11:15 AM -12:15 PM.
Poster F1-3966: "Novel Polymyxin Derivatives are Effective in Treating Peritoneal E.coli Infection in Mice", C. VINGSBO LUNDBERG 1, T. VAARA 2, N. FRIMODT-M0LLER 1, M. VAARA 2; 1Statens Serum Inst., Copenhagen, Denmark, 2Northern Antibiotics Ltd, Helsinki, Finland
Poster FI-3997: "Pharmacokinetics (PK) of Novel Anti-Gram-negative (G-) Antibiotics in Rats", F. E. A. ALI 1, G. CAO 1, A. POUDYAL 1, T. VAARA 2, R. L. NATION 1, M. VAARA 2, J. LI 1; 1Facility for Anti-infective Drug Dev. & Innovation, Monash Univ., Melbourne, Australia, 2Northern Antibiotics Ltd, Helsinki, Finland
Professor Martti Vaara, CEO and co-founder of Northern Antibiotics
Ltd., commented, "Multidrug-resistant enteric bacteria are emerging at an
alarming rate. This is a serious concern, since enteric bacteria are
responsible for more than 80% of all the hospital infections caused by
|SOURCE Northern Antibiotics Ltd|
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