Skip Navigation

This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (10)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Benkoó, I.
Right arrow Articles by Kovács, P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Benkoó, I.
Right arrow Articles by Kovács, P.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Journal of Antimicrobial Chemotherapy (1999) 43, 675-681
© 1999 The British Society for Antimicrobial Chemotherapy

Comparison of the toxicity of fluconazole and other azole antifungal drugs to murine and human granulocyte -macrophage progenitor cells in vitro

I. Benkoo*,a, F. Hernádia, A. Megyeria, A. Kissb, G. Somogyic, Z. Tegyeyd, F. Kraicsovitsd and P. Kovácsa

a Department of Pharmacology; b Second Department of Internal Medicine and; c Department of Forensic Medicine, University Medical School, Debrecen H-4012 POB 12; d Central Chemical Research Institute of the Hungarian Academy of Sciences, Budapest, Hungary

We studied the inhibitory effects on colony formation by granulocyte- macrophage colony forming units (cfu-gm) of eight azole antifungal agents in vitro. All agents, except fluconazole, inhibited colony formation dose-dependently with 50% inhibitory concentrations (IC 50) in the range of 0.78-49 µmol/L in cultures of murine and human bone marrow. For human cells, the IC 50 values were 0.553 mg/L for itraconazole, 1.24 mg/L for saperconazole, 2.58 mg/L for clotrimazole, 5.33 mg/L for miconazole, 6.17 mg/L for econazole, 6.27 mg/L for ketoconazole and 8.38 mg/L for oxiconazole. The IC 50 of itraconazole for human cfu-gm in vitro was similar to the plasma level of this drug recommended for systemic antifungal therapy (>0.5 mg/L) thus indicating the potential clinical relevance of our data. The IC 50 of ketoconazole for human cfu-gm in vitro may be exceeded by plasma levels produced in vivo by high (>=400 mg) doses, whereas fluconazole failed to reduce colony formation by 50% even at 100 mg/L, a concentration not reached in vivo even after extremely high doses (2000 mg/day). To most of the drugs studied, murine progenitor cells seemed to be less sensitive than the human ones. There was, however, a close correlation between the murine and human log IC 50 values of the drugs (r 2= 0.964, P< 0.001), suggesting that cultures of murine bone marrow may be suitable to predict the in-vitro toxicity of azole antifungals to human cfu-gm.

* Corresponding author. Tel and Fax: +36-52-427-899; E-mail: benko{at}king.pharmacol.dote.hu


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Eur J EndocrinolHome page
M. Riedl, C. Maier, G. Zettinig, P. Nowotny, W. Schima, and A. Luger
Long term control of hypercortisolism with fluconazole: case report and in vitro studies.
Eur. J. Endocrinol., April 1, 2006; 154(4): 519 - 524.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.