Evaluation of tigecycline penetration into colon wall tissue and epithelial lining fluid using a population pharmacokinetic model and Monte Carlo simulation.

Evaluation of tigecycline penetration into colon wall tissue and epithelial lining fluid using a population pharmacokinetic model and Monte Carlo simulation. Research Abstract Details 

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Evaluation of tigecycline penetration into colon wall tissue and epithelial lining fluid using a population pharmacokinetic model and Monte Carlo simulation. Abstract Text:

Christopher M Rubino,Lei Ma,Sujata M Bhavnani,Joan Korth-Bradley,John Speth,Evelyn Ellis-Grosse,Keith R Rodvold,Paul G Ambrose,George L Drusano,Christopher M Rubino,Lei Ma,Sujata M Bhavnani,Joan Korth-Bradley,John Speth,Evelyn Ellis-Grosse,Keith R Rodvold,Paul G Ambrose,George L Drusano,

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 r(2) 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.

Evaluation of tigecycline penetration into colon wall tissue and epithelial lining fluid using a population pharmacokinetic model and Monte Carlo simulation. Publishing Authors By Initials

CM Rubino,L Ma,SM Bhavnani,J Korth-Bradley,J Speth,E Ellis-Grosse,KR Rodvold,PG Ambrose,GL Drusano,CM Rubino,L Ma,SM Bhavnani,J Korth-Bradley,J Speth,E Ellis-Grosse,KR Rodvold,PG Ambrose,GL Drusano,

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Evaluation of tigecycline penetration into colon wall tissue and epithelial lining fluid using a population pharmacokinetic model and Monte Carlo simulation. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Antimicrobial agents and chemotherapy

VOLUME: 51

Page Numbers: 4085-9

Journal Abbreviation: Antimicrob. Agents Chemother.

ISSN: 0066-4804

DAY: 10

MONTH: 09

YEAR: 2007

Evaluation of tigecycline penetration into colon wall tissue and epithelial lining fluid using a population pharmacokinetic model and Monte Carlo simulation. Information

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LANGUAGE: eng

NlmUniqueID: 315061

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AFFILIATION: Institute for Clinical Pharmacodynamics, Ordway Research Institute, 150 New Scotland Avenue, Albany, NY 12208, USA.

Country: United States

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MEDLINETA: Antimicrob Agents Chemother

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