AAC
Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
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 HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Krieter, P.
Right arrow Articles by Courtney, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Krieter, P.
Right arrow Articles by Courtney, R.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, September 2004, p. 3543-3551, Vol. 48, No. 9
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.9.3543-3551.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Disposition of Posaconazole following Single-Dose Oral Administration in Healthy Subjects

Philip Krieter,1 Brian Flannery,1 Timothy Musick,2 Mark Gohdes,2 Monika Martinho,1 and Rachel Courtney1*

Schering-Plough Research Institute, Kenilworth, New Jersey,1 Covance Laboratories, Madison, Wisconsin2

Received 5 November 2003/ Returned for modification 30 December 2003/ Accepted 2 April 2004

Posaconazole is a potent, broad-spectrum triazole antifungal agent currently in clinical development for the treatment of refractory invasive fungal infections. Eight healthy male subjects received a single 399-mg (81.7 µCi) oral dose of [14C]posaconazole after consuming a high-fat breakfast. Urine, feces, and blood samples were collected for up to 336 h postdose and assayed for total radioactivity; plasma and urine samples were also assayed for parent drug. Posaconazole was orally bioavailable, with a median maximum posaconazole concentration in plasma achieved by 10 h postdose. Thereafter, posaconazole was slowly eliminated, with a mean half-life of 20 h. The greatest peak in the radioactivity profile of pooled plasma extracts was due to posaconazole, with smaller peaks due to a monoglucuronide, a diglucuronide, and a smaller fragment of the molecule. The mean total amount of radioactivity recovered was 91.1%; the cumulative excretion of radioactivity in feces and in urine was 76.9 and 14.0% of the dose, respectively. Most of the fecal radioactivity was associated with posaconazole, which accounted for 66.3% of the administered dose; however, urine contained only trace amounts of unchanged posaconazole. The radioactivity profile of pooled urine extracts included two monoglucuronide conjugates and a diglucuronide conjugate of posaconazole. These observations suggest that oxidative (phase 1) metabolism by cytochrome P450 isoforms represents only a minor route of elimination for posaconazole, and therefore cytochrome P450-mediated drug interactions should have a limited potential to impact posaconazole pharmacokinetics.

* Corresponding author. Mailing address: Early Clinical Research and Experimental Medicine, Schering-Plough Research Institute, K-15-4-4455, 2015 Galloping Hill Rd., Kenilworth, NJ 07033. Phone: (908) 740-3836. Fax: (908) 740-2169. E-mail: rachel.courtney{at}spcorp.com.

Antimicrobial Agents and Chemotherapy, September 2004, p. 3543-3551, Vol. 48, No. 9
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.9.3543-3551.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:



Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
Clin. Vaccine Immunol. Clin. Microbiol. Rev.
J. Clin. Microbiol. ALL ASM JOURNALS

Copyright © 2004 by the American Society for Microbiology. All rights reserved.