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Penetration of Vancomycin into Epithelial Lining Fluid in Healthy Volunteers
Open accessAbstract
Although vancomycin is often regarded as an agent that concentrates poorly in the lower respiratory tract, as determined from concentrations in epithelial lining fluid (ELF), few data are available. This study sought to determine the profile of vancomycin exposure in the ELF relative to plasma. Population modeling and Monte Carlo simulation were employed to estimate the penetration of vancomycin into ELF. Plasma and ELF pharmacokinetic (PK) data were obtained from 10 healthy volunteers. Concentration-time profiles in plasma and ELF were simultaneously modeled using a three-compartment model with zero-order infusion and first-order elimination and transfer using the big nonparametric adaptive grid (BigNPAG) program. Monte Carlo simulation with 9,999 subjects was performed to calculate the ELF/plasma penetration ratios by estimating the area under the concentration-time curve (AUC) in ELF (AUC ELF ) and plasma (AUC plasma ) after a single simulated 1,000-mg dose. The mean (standard deviation) AUC ELF /AUC plasma penetration ratio was 0.675 (0.677), and the 25th, 50th, and 75th percentile penetration ratios were 0.265, 0.474, and 0.842, respectively. Our results indicate that vancomycin penetrates ELF at approximately 50% of plasma levels. To properly judge the adequacy of current doses and schedules employed in practice, future studies are needed to delineate the PK/PD (pharmacodynamics) target for vancomycin in ELF. If the PK/PD target in ELF is found to be consistent with the currently proposed target of an AUC/MIC of ≥400, suboptimal probability of target attainment would be expected when vancomycin is utilized for pneumonias due to MRSA (methicillin-resistant Staphylococcus aureus ) with MICs in excess of 1 mg/liter.
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Under the assumption that cell membrane composition is similar in different species, the specific PStc value (9.15 × 10^-5 mL/s/mL cell volume) fitted against rat data was used with human physiology to accurately predict pharmacokinetics in humans.
“Under the assumption that cell membrane composition is similar in different species, the specific PStc value (9.15 × 10 -5 mL/s/mL cell volume) fitted against rat data was used with human physiology to accurately predict pharmacokinetics in humans [85] (Fig. 11).”
From Physiologically Based Pharmacokinetic Modelling for First-In-Human Predictions: An Updated Model Building Strategy Illustrated with Challenging Industry Case Studies (2019) · cites this paper as [85]
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Miller, N. A., Reddy, M. B., Heikkinen, A. T., Lukacova, V., & Parrott, N. (2019) · Clinical Pharmacokinetics · doi:10.1007/s40262-019-00741-9 · Cited by 142
Metadata
- Authors
- Lodise, T. P., Drusano, G. L., Butterfield, J. M., Scoville, J., Gotfried, M., & Rodvold, K. A.
- Affiliations
- Albany College of Pharmacy and Health Sciences (US)
- Ordway Research Institute, Albany, New York
- University of Arizona (US)
- University of Illinois Chicago (US)
- Corresponding author
- Lodise, Thomas P.
- Venue
- Antimicrobial Agents and Chemotherapy
- Publisher
- American Society for Microbiology
- Published
- 2011-12
- Volume
- 55
- Issue
- 12
- Pages
- 5507-5511
- ISSN
- 0066-4804 (ISSN-L)
- 1098-6596
- PMC
- PMC3232765
- OpenAlex
- W2109063989
- Cited by
- 60
- References
- 21
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 4 · 2023: 3 · 2022: 1 · 2021: 4 · 2020: 3 · 2019: 5 · 2018: 3 · 2017: 4 · 2016: 3 · 2015: 5 · 2014: 8 · 2013: 5 · 2012: 6
- FWCI
- 4.45
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Antimicrobial Agents and Chemotherapy (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Antibiotics Pharmacokinetics and Efficacy
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmaceutical studies and practices
- Health Sciences › Medicine › Epidemiology › Pneumonia and Respiratory Infections
- Keywords
- vancomycin, epithelial lining fluid, drug penetration, lower respiratory tract, plasma pharmacokinetics, penetration ratio, Monte Carlo simulation, population pharmacokinetic model, MRSA pneumonia, pharmacokinetic/pharmacodynamic targets, healthy volunteers
- MeSH terms
- Adult, Anti-Bacterial Agents, Bronchoalveolar Lavage Fluid, Bronchoscopy, Epithelium, Female, Humans, Male, Microbial Sensitivity Tests, Models, Biological, Monte Carlo Method, Vancomycin, Area Under Curve, Methicillin-Resistant Staphylococcus aureus, Young Adult
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