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, October 2006, p. 3418-3423, Vol. 50, No. 10
0066-4804/06/$08.00+0     doi:10.1128/AAC.00241-06

Compartmentalized Intrapulmonary Pharmacokinetics of Amphotericin B and Its Lipid Formulations

Andreas H. Groll,1,4 Caron A. Lyman,1 Vidmantas Petraitis,1 Ruta Petraitiene,1 Derek Armstrong,1 Diana Mickiene,1 Raul M. Alfaro,2 Robert L. Schaufele,1 Tin Sein,1 John Bacher,3 and Thomas J. Walsh1*

Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute, Bethesda, Maryland,1 Pharmacokinetics Research Laboratory, Pharmacy Department, Warren Grant Magnuson Clinical Center, Bethesda, Maryland,2 Division of Veterinary Resources, National Institutes of Health, Bethesda, Maryland,3 Infectious Disease Research Program, Center for Bone Marrow Transplantation and Department of Pediatric Hematology/Oncology, University Children's Hospital, Muenster, Germany4

Received 24 February 2006/ Returned for modification 2 May 2006/ Accepted 18 June 2006

We investigated the compartmentalized intrapulmonary pharmacokinetics of amphotericin B and its lipid formulations in healthy rabbits. Cohorts of three to seven noninfected, catheterized rabbits received 1 mg of amphotericin B deoxycholate (DAMB) per kg of body weight or 5 mg of either amphotericin B colloidal dispersion (ABCD), amphotericin B lipid complex (ABLC), or liposomal amphotericin B (LAMB) per kg once daily for a total of 8 days. Following sparse serial plasma sampling, rabbits were sacrificed 24 h after the last dose, and epithelial lining fluid (ELF), pulmonary alveolar macrophages (PAM), and lung tissue were obtained. Pharmacokinetic parameters in plasma were derived by model-independent techniques, and concentrations in ELF and PAM were calculated based on the urea dilution method and macrophage cell volume, respectively. Mean amphotericin B concentrations ± standard deviations (SD) in lung tissue and PAM were highest in ABLC-treated animals, exceeding concurrent plasma levels by 70- and 375-fold, respectively (in lung tissue, 16.24 ± 1.62 versus 2.71 ± 1.22, 6.29 ± 1.17, and 6.32 ± 0.57 µg/g for DAMB-, ABCD-, and LAMB-treated animals, respectively [P = 0.0029]; in PAM, 89.1 ± 37.0 versus 8.92 ± 2.89, 5.43 ± 1.75, and 7.52 ± 2.50 µg/ml for DAMB-, ABCD-, and LAMB-treated animals, respectively [P = 0.0246]). By comparison, drug concentrations in ELF were much lower than those achieved in lung tissue and PAM. Among the different cohorts, the highest ELF concentrations were found in LAMB-treated animals (2.28 ± 1.43 versus 0.44 ± 0.13, 0.68 ± 0.27, and 0.90 ± 0.28 µg/ml in DAMB-, ABCD-, and ABLC-treated animals, respectively [P = 0.0070]). In conclusion, amphotericin B and its lipid formulations displayed strikingly different patterns of disposition in lungs 24 h after dosing. Whereas the disposition of ABCD was overall not fundamentally different from that of DAMB, ABLC showed prominent accumulation in lung tissue and PAM, while LAMB achieved the highest concentrations in ELF.

* Corresponding author. Mailing address: CRC-1-5750, 10 Center Drive, Bethesda, MD 20892. Phone: (301) 402-0023. Fax: (301) 480-2308. E-mail: walsht{at}mail.nih.gov.

Antimicrobial Agents and Chemotherapy, October 2006, p. 3418-3423, Vol. 50, No. 10
0066-4804/06/$08.00+0     doi:10.1128/AAC.00241-06




This article has been cited by other articles:

  • Weiler, S., Falkensammer, G., Hammerer-Lercher, A., Anliker, M., Vogelsinger, H., Joannidis, M., Dunzendorfer, S., Stein, M., Bellmann, R. (2009). Pulmonary Epithelial Lining Fluid Concentrations after Use of Systemic Amphotericin B Lipid Formulations. Antimicrob. Agents Chemother. 53: 4934-4937 [Abstract] [Full Text]  
  • Dotis, J., Simitsopoulou, M., Dalakiouridou, M., Konstantinou, T., Panteliadis, C., Walsh, T. J., Roilides, E. (2008). Amphotericin B formulations variably enhance antifungal activity of human neutrophils and monocytes against Fusarium solani: comparison with Aspergillus fumigatus. J Antimicrob Chemother 61: 810-817 [Abstract] [Full Text]  
  • Weiler, S., Bellmann-Weiler, R., Joannidis, M., Bellmann, R. (2007). Penetration of Amphotericin B Lipid Formulations into Pleural Effusion. Antimicrob. Agents Chemother. 51: 4211-4213 [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»