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 ASM journals
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 Rubino, C. M.
Right arrow Articles by Drusano, G. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Rubino, C. M.
Right arrow Articles by Drusano, G. L.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, November 2007, p. 4085-4089, Vol. 51, No. 11
0066-4804/07/$08.00+0     doi:10.1128/AAC.00065-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Evaluation of Tigecycline Penetration into Colon Wall Tissue and Epithelial Lining Fluid Using a Population Pharmacokinetic Model and Monte Carlo Simulation{triangledown}

Christopher M. Rubino,1,2 Lei Ma,2 Sujata M. Bhavnani,1,2 Joan Korth-Bradley,3 John Speth,3 Evelyn Ellis-Grosse,4 Keith R. Rodvold,5 Paul G. Ambrose,1,2* and George L. Drusano1,2

Institute for Clinical Pharmacodynamics, Albany, New York,1 Ordway Research Institute, Albany, New York,2 Wyeth Research, Philadelphia, Pennsylvania,3 e2g Biopharmaceutical Consulting, Downingtown, Pennsylvania,4 Colleges of Pharmacy and Medicine, University of Illinois at Chicago, Chicago, Illinois5

Received 16 January 2007/ Returned for modification 7 March 2007/ Accepted 28 August 2007

The objective of these analyses was to assess the penetration of tigecycline into colon wall tissue and epithelial lining fluid (ELF). The analyses included data from subjects without infection (phase 1) and patients with intra-abdominal infections (phase 2/3). Steady-state serum samples were collected from all subjects/patients (n = 577), while colon wall specimens (n = 23) and ELF specimens (n = 30) were obtained from subjects without infection. Tissue and serum data were simultaneously comodeled by using the BigNPAG program, and a four-compartment, open model with zero-order intravenous input and first-order elimination was employed. To examine the full range of tissue penetration and the associated probabilities of occurrence, a 9,999-subject Monte Carlo simulation was performed with two outputs, one for ELF penetration and one for colon wall tissue penetration. Data were well fit using models described above, with all r2 values above 0.95. For subjects without infection, the median (5th and 95th percentiles) colon wall and ELF penetration ratios were 1.73 (0.160 and 199) and 1.15 (0.561 and 5.23), respectively. Simulation results predict that tissue penetration varies considerably and likely explain unexpected clinical outcomes for those patients infected with strains at margins of the MIC distribution.

* Corresponding author. Mailing address: FIDSA, Institute for Clinical Pharmacodynamics, Ordway Research Institute, 150 New Scotland Avenue, Albany, NY 12208. Phone: (518) 641-6472. Fax: (518) 641-6303. E-mail: pambrose-ICPD{at}ordwayresearch.org

{triangledown} Published ahead of print on 10 September 2007.

Antimicrobial Agents and Chemotherapy, November 2007, p. 4085-4089, Vol. 51, No. 11
0066-4804/07/$08.00+0     doi:10.1128/AAC.00065-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Bhavnani, S. M., Rubino, C. M., Ambrose, P. G., Babinchak, T. J., Korth-Bradley, J. M., Drusano, G. L. (2010). Impact of Different Factors on the Probability of Clinical Response in Tigecycline-Treated Patients with Intra-Abdominal Infections. Antimicrob. Agents Chemother. 54: 1207-1212 [Abstract] [Full Text]  
  • Zhanel, G. G., Baudry, P. J., Tailor, F., Cox, L., Hoban, D. J., Karlowsky, J. A. (2009). Determination of the pharmacodynamic activity of clinically achievable tigecycline serum concentrations against clinical isolates of Escherichia coli with extended-spectrum {beta}-lactamases, AmpC {beta}-lactamases and reduced susceptibility to carbapenems using an in vitro model. J Antimicrob Chemother 64: 824-828 [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»