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 Groll, A. H.
Right arrow Articles by Walsh, T. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Groll, A. H.
Right arrow Articles by Walsh, T. J.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, December 2001, p. 3322-3327, Vol. 45, No. 12
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.12.3322-3327.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Compartmental Pharmacokinetics and Tissue Distribution of the Antifungal Echinocandin Lipopeptide Micafungin (FK463) in Rabbits

Andreas H. Groll,1 Diana Mickiene,1 Vidmantas Petraitis,1 Ruta Petraitiene,1 Khalid H. Ibrahim,2 Stephen C. Piscitelli,2 Ihor Bekersky,3 and Thomas J. Walsh1,*

Immunocompromised Host Section, Pediatric Oncology Branch National Cancer Institute,1 and Pharmacokinetics Research Laboratory, Pharmacy Department, Warren Grant Magnuson Clinical Center,2 National Institutes of Health, Bethesda, Maryland, and Fujisawa Healthcare USA, Deerfield, Illinois3

Received 20 February 2001/Returned for modification 21 July 2001/Accepted 20 September 2001

The plasma pharmacokinetics and tissue distribution of the novel antifungal echinocandin-like lipopeptide micafungin (FK463) were investigated in healthy rabbits. Cohorts of three animals each received micafungin at 0.5, 1, and 2 mg/kg of body weight intravenously once daily for a total of 8 days. Serial plasma samples were collected on days 1 and 7, and tissue samples were obtained 30 min after the eighth dose. Drug concentrations were determined by validated high-performance liquid chromatographic methods. Plasma drug concentration data were fit to a two-compartment pharmacokinetic model, and pharmacokinetic parameters were estimated using weighted nonlinear least-square regression analysis. Micafungin demonstrated linear plasma pharmacokinetics without changes in total clearance and dose-normalized area under the concentration-time curve from 0 h to infinity. After administration of single doses to the rabbits, mean peak plasma drug concentrations ranged from 7.62 µg/ml at 0.5 mg/kg to 16.8 µg/ml at 2 mg/kg, the area under the concentration-time curve from 0 to 24 h ranged from 5.66 to 21.79 µg · h/ml, the apparent volume of distribution at steady state ranged from 0.296 to 0.343 liter/kg, and the elimination half-life ranged from 2.97 to 3.20 h, respectively. No significant changes in pharmacokinetic parameters and no accumulation was noted after multiple dosing. Mean tissue micafungin concentrations 30 min after the last of eight daily doses were highest in the lung (2.26 to 11.76 µg/g), liver (2.05 to 8.82 µg/g), spleen (1.87 to 9.05 µg/g), and kidney (1.40 to 6.12 µg/g). While micafungin was not detectable in cerebrospinal fluid, the concentration in brain tissue ranged from 0.08 to 0.18 µg/g. These findings indicate linear disposition of micafungin at dosages of 0.5 to 2 mg/kg and achievement of potentially therapeutic drug concentrations in plasma and tissues that are common sites of invasive fungal infections.

* Corresponding author. Mailing address: Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Building 10, Rm. 13N240, 10, Center Dr., Bethesda, MD 20892. Phone: (301) 402-0023. Fax: (301) 402-0575. E-mail: walsht{at}mail.nih.gov.

Antimicrobial Agents and Chemotherapy, December 2001, p. 3322-3327, Vol. 45, No. 12
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.12.3322-3327.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Nicasio, A. M., Tessier, P. R., Nicolau, D. P., Knauft, R. F., Russomanno, J., Shore, E., Kuti, J. L. (2009). Bronchopulmonary Disposition of Micafungin in Healthy Adult Volunteers. Antimicrob. Agents Chemother. 53: 1218-1220 [Abstract] [Full Text]  
  • Cao, C., Liu, W., Li, R., Wan, Z., Qiao, J. (2009). In vitro interactions of micafungin with amphotericin B, itraconazole or fluconazole against the pathogenic phase of Penicillium marneffei. J Antimicrob Chemother 63: 340-342 [Abstract] [Full Text]  
  • Petraitiene, R., Petraitis, V., Hope, W. W., Mickiene, D., Kelaher, A. M., Murray, H. A., Mya-San, C., Hughes, J. E., Cotton, M. P., Bacher, J., Walsh, T. J. (2008). Cerebrospinal Fluid and Plasma (1->3)-{beta}-D-Glucan as Surrogate Markers for Detection and Monitoring of Therapeutic Response in Experimental Hematogenous Candida Meningoencephalitis. Antimicrob. Agents Chemother. 52: 4121-4129 [Abstract] [Full Text]  
  • Meletiadis, J., Chanock, S., Walsh, T. J. (2006). Human Pharmacogenomic Variations and Their Implications for Antifungal Efficacy. Clin. Microbiol. Rev. 19: 763-787 [Abstract] [Full Text]  
  • Seibel, N. L., Schwartz, C., Arrieta, A., Flynn, P., Shad, A., Albano, E., Keirns, J., Lau, W. M., Facklam, D. P., Buell, D. N., Walsh, T. J. (2005). Safety, Tolerability, and Pharmacokinetics of Micafungin (FK463) in Febrile Neutropenic Pediatric Patients. Antimicrob. Agents Chemother. 49: 3317-3324 [Abstract] [Full Text]  
  • Serena, C., Fernandez-Torres, B., Pastor, F. J., Trilles, L., Lazera, M. d. S., Nolard, N., Guarro, J. (2005). In Vitro Interactions of Micafungin with Other Antifungal Drugs against Clinical Isolates of Four Species of Cryptococcus. Antimicrob. Agents Chemother. 49: 2994-2996 [Abstract] [Full Text]  
  • Petraitis, V., Petraitiene, R., Groll, A. H., Roussillon, K., Hemmings, M., Lyman, C. A., Sein, T., Bacher, J., Bekersky, I., Walsh, T. J. (2002). Comparative Antifungal Activities and Plasma Pharmacokinetics of Micafungin (FK463) against Disseminated Candidiasis and Invasive Pulmonary Aspergillosis in Persistently Neutropenic Rabbits. Antimicrob. Agents Chemother. 46: 1857-1869 [Abstract] [Full Text]  


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