Navigation Links
Northern Antibiotics Presents New Data on Novel Polymyxin Compounds at the Joint ICAAC/IDSA 2008
Date:10/28/2008

HELSINKI, October 28 /PRNewswire/ -- Northern Antibiotics Ltd., the developer of novel polymyxin derivatives for the treatment of infections caused by multidrug-resistant Gram-negative bacteria, revealed today animal efficacy and pharmacokinetic data from their NAB compounds at the 48th Annual ICAAC/IDSA 46th Annual Meeting in Washington, DC.

Northern Antibiotics has developed two series of novel polymyxin (NAB) compounds (Vaara M. et al., 2008, Antimicrob. Agents Chemother. 52:3229). The compounds of the first series (lead compound, NAB739) are directly antibacterial against polymyxin-susceptible Gram-negative enteric bacteria such as Escherichia coli, Klebsiella spp, and Enterobacter spp., as well as against Acinetobacter baumannii. The representatives of the second series (lead compound, NAB7061) have only a weak direct action but sensitize in a very remarkable degree these Gram negative bacteria to antibiotics such as macrolides, rifampin, and others. The compounds of both series carry only three positive charges whereas the notoriously nephrotoxic old polymyxins (colistin, polymyxin B) carry a total of five positive charges.

The in vivo efficacy of NAB739 and NAB7061 was evaluated in a murine peritoneal infection model using the virulent, encapsulated E. coli strain IH3080 (K1:O18) as the challenge organism. As low a dose as 1 mg/kg (body weight) of NAB739, given at 1h postinfection and repeated at 3 h postinfection, displayed potent bactericidal effect. The bacterial counts in the treated animals were 4.8 log10 lower in the mice treated with NAB739 than in the untreated control mice.

Furthermore, while NAB7061 (5 mg/kg) alone as well as erythromycin (20 mg/kg) alone were ineffective in the murine peritoneal model, the bacterial counts in mice that received their combination were 2.9 log10 lower than in the untreated controls (dosing time schedule as above with NAB739). Accordingly, the in vivo efficacy studies corroborate the previous in vitro findings.

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 Gram-negative bacteria. Our NAB compounds have the potential to become a new treatment against these bacteria".

About Northern Antibiotics Ltd.

Founded in 2003 and headquartered in Helsinki, Finland, Northern Antibiotics Ltd. is engaged in the discovery and development of novel antibiotics against multidrug-resistant Gram-negative bacteria. The NAB compounds are polymyxin derivatives that have less cationic charges than the polymyxins currently in clinical use. This difference is believed to result in reduced nephrotoxicity of the novel compounds. For more information, visit http://www.northernantibiotics.com.

Contact:

Dr. Barry Mason

Business Development Consultant

Email: barry.mason@northernantibiotics.com

Phone: +44(0)1625-858396

Mobile: +44(0)7713-261356


'/>"/>
SOURCE Northern Antibiotics Ltd
Copyright©2008 PR Newswire.
All rights reserved

Related biology technology :

1. GlaxoSmithKline and Anacor Pharmaceuticals Form Alliance to Develop Systemic Antivirals and Antibiotics Based on Boron Chemistry
2. Drugs from Johnson & Johnson/Basilea and Forest Are the Most Promising Antibiotics in the Community-Acquired Pneumonia Pipeline
3. Solving the Z rings mysteries may lead to new antibiotics
4. Skin & Aging Article Finds Derma Sciences MEDIHONEY(TM) Helps to Promote Healing Where Antibiotics Fail
5. Nektar Receives Patent Covering Pulmonary Targeted Antibiotics
6. Trius Awarded $28 Million Contract to Develop Novel Antibiotics
7. Lexicon Presents Class of Compounds Modulating TPH1, the Target for its LX1031 Investigational Drug for Irritable Bowel Syndrome
8. Touching 418 Billion Lives, Hepatitis Still Presents Significant Threat to Global Health
9. Touching 418 Million Lives, Hepatitis Still Presents Significant Threat to Global Health
10. Nektar Presents Positive Results from Phase 1 Clinical Trial of NKTR-118 (oral PEG-naloxol) at American College of Clinical Pharmacology Meeting
11. Sangamo BioSciences Presents Data Demonstrating In Vivo Protection Against HIV Infection by CCR5-ZFN Therapeutic
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:3/1/2017)... ... March 01, 2017 , ... Ace Laboratories, ... into clinical applications, announces the formation of its Scientific and Clinical Advisory Board. ... the drug which has been discussed in the media as “the red wine ...
(Date:2/28/2017)... ... , ... Surface Plasmon Resonance (SPR) is a widely-used, label-free technique to characterize ... changes in the dielectric properties of the medium close to a metal surface. ... to 300 nm above the metal surface (Au) and thus by the material absorbed ...
(Date:2/28/2017)... NEW YORK , Feb. 28, 2017 /PRNewswire/ ... company, announced today the formation of the Phosphorus ... and science experts chosen to advise the company ... company,s large-scale, multi-site research initiatives. Please visit ... team and initiatives. "We,ve gathered some ...
(Date:2/28/2017)... -- Xencor, Inc. (NASDAQ: XNCR), a clinical-stage biopharmaceutical company developing ... diseases, asthma and allergic diseases and cancer, today ... full year ended December 31, 2016 and provided ... clinical highlights. "During 2016, we made ... starting five clinical trials across our XmAb portfolio.  ...
Breaking Biology Technology:
(Date:2/14/2017)... , Feb. 14, 2017  Wake Forest Baptist ... as its new chief executive officer (CEO). Freischlag joins ... John D. McConnell , M.D., who last year ... at the Medical Center, after leading it since 2008. ... full scope of Wake Forest Baptist,s academic health system, ...
(Date:2/10/2017)... Research and Markets has announced ... - Scientific and Commercial Aspects" to their offering. ... Biomarkers ... with therapy for selection of treatment as well for monitoring ... of disease in modern medicine. Biochip/microarray technologies and next generation ...
(Date:2/8/2017)... BEDFORD, Mass., Feb. 7, 2017  Aware, Inc. (NASDAQ: ... services, today reported financial results for its quarter and year ... fourth quarter of 2016 was $3.9 million compared to $6.9 ... the fourth quarter of 2016 was $0.6 million compared to ... in the fourth quarter of 2016 was $0.5 million, or ...
Breaking Biology News(10 mins):