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Expert Opinion on Investigational Drugs Volume 12, 2003 - Issue 2
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Miscellaneous

Development potential of rifalazil

David M Rothstein ActivBiotics, Inc., 198 Broadway, Cambridge, MA 02139, USA. [email protected]
,
Arthur D Hartman Hartman Medical Communications, Inc., Downingtown, PA, USA
,
Michael H Cynamon Upstate Medical University, State University of New York, Syracuse, NY, USA
&
Barry I Eisenstein ActivBiotics, Inc., 198 Broadway, Cambridge, MA 02139, USA
Pages 255-271 | Published online: 02 Mar 2005

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  • ••The mechanism of action of rifalazil, theinhibition of prokaryotic RNA polymerase, is characterised.
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  • •The conservation of RNA polymerases particularly in proximity to the rifampin-binding site is described.
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  • •Mutants are described carrying lesions conferring resistance to rifampin and cross-resistance to rifalazil.
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  • ••This paper describes rifalazil's uniqueability to eradicate Chlamydia in tissue culture, not permitting survival of persistent forms.
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  • •In vinv activity of rifalazil against H pylori is described.
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  • ••The most extensive animal pharmacologystudy of rifalazil is presented.
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  • •Metabolites of rifalazil from in vivo studies including a human clinical trial are identified.
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  • •Antibacterial activity of rifalazil metabolites is described.
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  • ••The lack of significant interaction ofrifalazil with the P450 system contrasts to the interaction of rifampin with the P450 system.
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  • •Antimycobacterial activity of rifalazil is presented.
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  • •Activity of rifalazil in an animal model for TB is described.
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  • •Eradication of Mycobacteria by rifalazil combined with isoniazid in a longer term animal study is presented.
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  • ••Eradication of Mycobacteria in an animalmodel was challenged by dosing animals with immunosuppressive drugs.
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  • •Evidence that rifalazil has activity in vivo against M avium is presented.
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  • •Cross-resistance of rifampin-resistant mutants of S. aureus to rifalazil are included.
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  • •Alternative therapies for the treatment of H pylori, including the use of the ansamycin rifabutin, are included.
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  • •A strong case for latent Chlamydia trachomatis infections in humans is made.
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  • ••This article contains an excellent summaryof the relationship of inflammation and atherosclerosis.
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  • •A good summary of current information of atherosclerosis risk factors.
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  • •This paper summarises the association between atherosclerosis and bacterial infections, particularly Chlamydia.
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  • ••The authors emphasise the methods thatmay be employed to further elucidate the role of C. pneumoniae in atherosclerosis.
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Websites

  • www.tballiance.com The Economics of TB Drug Development, Global Alliance for TB Drug Development (October 2001).
  • www.salixltd.com SALIX, Ltd homepage.

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