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
Right arrow Citation Map
Services
Right arrow E-mail this article to a friend
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 HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Martin, D. E.
Right arrow Articles by Ballow, C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Martin, D. E.
Right arrow Articles by Ballow, C.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, September 2007, p. 3063-3066, Vol. 51, No. 9
0066-4804/07/$08.00+0     doi:10.1128/AAC.01391-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Safety and Pharmacokinetics of Bevirimat (PA-457), a Novel Inhibitor of Human Immunodeficiency Virus Maturation, in Healthy Volunteers{triangledown}

David E. Martin,1* Robert Blum,2 John Wilton,3 Judy Doto,1 Hal Galbraith,4 Gina L. Burgess,4 Philip C. Smith,5 and Charles Ballow2

Panacos Pharmaceuticals, Inc., Gaithersburg, Maryland,1 Buffalo Clinical Research Center, Buffalo, New York,2 Emprexe Analytical LLC, Buffalo, New York,3 Quintiles Inc., Kansas City, Missouri,4 University of North Carolina, Chapel Hill, North Carolina5

Received 7 November 2006/ Returned for modification 7 March 2007/ Accepted 9 June 2007

Bevirimat (BVM; formerly known as PA-457) is a novel inhibitor of human immunodeficiency virus (HIV) maturation that is being developed for the treatment of HIV infection. The pharmacokinetics of this agent in healthy male volunteers were studied in a randomized, double-blind study in which the participants received single oral doses of placebo (n = 8) or escalating doses of BVM at 25, 50, 100, or 250 mg (n = 6 per dose); escalation was performed only after the pharmacokinetics and safety of the preceding dose had been evaluated. Plasma was collected over 480 h after dosing and urine was collected over 48 h after dosing for determination of the values of pharmacokinetic parameters. BVM was well absorbed after oral administration, with peak plasma concentrations being achieved 1 to 3 h after dosing. The half-life was 60 to 80 h. The exposure assessed by determination of the peak concentration and the area under the concentration-time curve was dose proportional. Single oral doses of BVM were well tolerated: there were no dose-limiting toxicities, and no serious adverse events were reported. These findings suggest that that BVM offers a favorable pharmacokinetic profile, with predictable pharmacokinetics following the oral administration of single doses. The long half-life of BVM may facilitate once-daily dosing.

* Corresponding author. Mailing address: Drug Development, Panacos Pharmaceuticals, 209 Perry Parkway, Suite 7, Gaithersburg, MD 20877. Phone: (240) 631-1395. Fax: (301) 208-8755. E-mail: dmartin{at}panacos.com

{triangledown} Published ahead of print on 18 June 2007.

Antimicrobial Agents and Chemotherapy, September 2007, p. 3063-3066, Vol. 51, No. 9
0066-4804/07/$08.00+0     doi:10.1128/AAC.01391-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Adamson, C. S., Waki, K., Ablan, S. D., Salzwedel, K., Freed, E. O. (2009). Impact of Human Immunodeficiency Virus Type 1 Resistance to Protease Inhibitors on Evolution of Resistance to the Maturation Inhibitor Bevirimat (PA-457). J. Virol. 83: 4884-4894 [Abstract] [Full Text]  
  • Connor, A., Evans, P., Doto, J., Ellis, C., Martin, D. E. (2009). An Oral Human Drug Absorption Study to Assess the Impact of Site of Delivery on the Bioavailability of Bevirimat. J Clin Pharmacol 49: 606-612 [Abstract] [Full Text]  
  • Smith, P. F., Ogundele, A., Forrest, A., Wilton, J., Salzwedel, K., Doto, J., Allaway, G. P., Martin, D. E. (2007). Phase I and II Study of the Safety, Virologic Effect, and Pharmacokinetics/Pharmacodynamics of Single-Dose 3-O-(3',3'-Dimethylsuccinyl)Betulinic Acid (Bevirimat) against Human Immunodeficiency Virus Infection. Antimicrob. Agents Chemother. 51: 3574-3581 [Abstract] [Full Text]  


Copyright © 2010 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»