This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Jiang, L.-J.
Right arrow Articles by Or, Y. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Jiang, L.-J.
Right arrow Articles by Or, Y. S.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, May 2009, p. 1786-1792, Vol. 53, No. 5
0066-4804/09/$08.00+0     doi:10.1128/AAC.01270-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Pharmacokinetics of EDP-420 after Ascending Single Oral Doses in Healthy Adult Volunteers{triangledown}

Li-Juan Jiang,* Michelle Wang, and Yat Sun Or

Enanta Pharmaceuticals, Inc., Watertown, Massachusetts 02472

Received 22 September 2008/ Returned for modification 27 December 2008/ Accepted 6 February 2009

EDP-420 (EP-013420, S-013420) is a first-in-class bicyclolide (bridged bicyclic macrolide) currently in clinical development for the treatment of respiratory tract infections. It has good preclinical pharmacokinetic properties across multiple species and potent in vitro and in vivo activity against respiratory tract infection pathogens, including Haemophilus influenzae, atypical organisms (e.g., Chlamydia pneumoniae, Mycoplasma pneumoniae, and Legionella pneumophila), and multidrug-resistant streptococci. The safety, tolerability, and pharmacokinetics of an orally administered EDP-420 suspension in 40 healthy adult subjects were assessed in a randomized, double-blind, placebo-controlled, ascending single-dose study. Eligible subjects were sequentially randomized into one of five study groups (i.e., 100-, 200-, 400-, 800-, or 1,200-mg dosing groups) consisting of eight subjects (six active and two placebo) each. EDP-420 was well tolerated. There were no serious adverse events reported, nor were there any dose-limiting clinical or laboratory adverse events reported. EDP-420 was rapidly absorbed after a single oral dose. The mean plasma terminal half-life ranged from 15.6 to 20.1 h with low clearance. At the 400-mg dose, the area under the curve was 14.4 µg·h/ml, which well exceeded the required area under the concentration-time curve to cover common respiratory tract infection pathogens based on preclinical pharmacokinetic/pharmacodynamic modeling. The long half-life and high systemic exposure of EDP-420 support once-daily dosing and may allow for shorter treatment durations compared to other macrolide antibiotics. Based on its human pharmacokinetic profiles, taken together with its in vitro/in vivo activity against common respiratory pathogens, EDP-420 warrants efficacy trials for the treatment of respiratory tract infections.

* Corresponding author. Mailing address: Enanta Pharmaceuticals, Inc., 500 Arsenal St., Watertown, MA 02472. Phone: (617) 607-0713. Fax: (617) 607-0534. E-mail: ljiang{at}enanta.com

{triangledown} Published ahead of print on 17 February 2009.

Antimicrobial Agents and Chemotherapy, May 2009, p. 1786-1792, Vol. 53, No. 5
0066-4804/09/$08.00+0     doi:10.1128/AAC.01270-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»