An Experimental Model for Measuring Middle Ear Antimicrobial Drug Penetration in Otitis Media

Gregg H. Jossart, Gary R. Erdmann, David G Levitt, Peter Kucera, Chap T Le, Steven S Juhn, G. Scott Giebink, Daniel M. Canafax

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Bacteria are an important cause of acute otitis media and successful treatment depends on achieving inhibitory or bacteriacidal antimicrobial drug concentrations in the middle ear. To evaluate further otitis media treatment success and failure, we developed a chinchilla model to study antimicrobial drug penetration through the middle ear mucosa. Using quantitative histomorphometry, we measured the middle ear space in 10 chinchillas and found a mean ±SD volume of 2.09 ± 0.08 ml and a mean SD surface area of 14.41 ± 1.48 cm2. To measure the apparent rate constant (Ke) of antibiotic elimination from the middle ear, through the middle ear mucosa, an antibiotic solution was inoculated into the middle ear cavity, and samples were aspirated between 1 and 8 hr later. In normal ears, the mean Ke ±SD for amoxicillin was 0.118 ± 0.013 hr−1, that for a trimethoprim 0.461 ± 0.090 hr−1, and that for sulfamethoxazole 0.265 ± 0.062 hr−1. In ears inoculated with type 7F Streptococcus pneumoniae to induce acute otitis media, the Ke ±SD increased for all three drugs (P < 0.05): amoxicillin to 0.286 ± 0.089 hr−1, trimethoprim to 0.662 ± 0.118 hr−1, and sulfamethoxazole to 0.411 ± 0.056 hr−1. These values demonstrate that amoxicillin had the lowest apparent penetration rate constant of the three antibiotics but the greatest increase from normal to infected mucosa (142%). Trimethoprim had the highest apparent penetration rate constant of the three antibiotics but the smallest increase from normal to infected mucosa (44%), while the sulfamethoxazone apparent penetration rate constant increased from normal to infected mucosa by 55%. The Ke for amoxicillin was the same for inoculation volumes of 0.8 and 1.6 ml (P = 0.557) and the same for sampling intervals of 4 and 8 hr (P = 0.054). All three antimicrobial drug concentration–time curves were log-linear, as predicted by Fick's first law of diffusion. In conclusion, this model overcomes the technical limitations of previous models and permits investigation of the many factors that can influence antibiotic penetration into the middle ear and reduce otitis media treatment efficacy.

Original languageEnglish (US)
Pages (from-to)1242-1247
Number of pages6
JournalPharmaceutical Research: An Official Journal of the American Association of Pharmaceutical Scientists
Volume7
Issue number12
DOIs
StatePublished - Jan 1 1990

Fingerprint

Otitis Media
Middle Ear
Amoxicillin
Theoretical Models
Trimethoprim
Anti-Bacterial Agents
Rate constants
Mucous Membrane
Sulfamethoxazole
Pharmaceutical Preparations
Chinchilla
Fick's laws
Ear
Bacteria
Streptococcus pneumoniae
Treatment Failure
Sampling

Keywords

  • amoxicillin
  • otitis media
  • pharmacokinetics
  • sulfamethoxazole
  • trimethoprim

Cite this

An Experimental Model for Measuring Middle Ear Antimicrobial Drug Penetration in Otitis Media. / Jossart, Gregg H.; Erdmann, Gary R.; Levitt, David G; Kucera, Peter; Le, Chap T; Juhn, Steven S; Giebink, G. Scott; Canafax, Daniel M.

In: Pharmaceutical Research: An Official Journal of the American Association of Pharmaceutical Scientists, Vol. 7, No. 12, 01.01.1990, p. 1242-1247.

Research output: Contribution to journalArticle

Jossart, Gregg H. ; Erdmann, Gary R. ; Levitt, David G ; Kucera, Peter ; Le, Chap T ; Juhn, Steven S ; Giebink, G. Scott ; Canafax, Daniel M. / An Experimental Model for Measuring Middle Ear Antimicrobial Drug Penetration in Otitis Media. In: Pharmaceutical Research: An Official Journal of the American Association of Pharmaceutical Scientists. 1990 ; Vol. 7, No. 12. pp. 1242-1247.
@article{9b35b35b06504a6a9828b75587ab60a8,
title = "An Experimental Model for Measuring Middle Ear Antimicrobial Drug Penetration in Otitis Media",
abstract = "Bacteria are an important cause of acute otitis media and successful treatment depends on achieving inhibitory or bacteriacidal antimicrobial drug concentrations in the middle ear. To evaluate further otitis media treatment success and failure, we developed a chinchilla model to study antimicrobial drug penetration through the middle ear mucosa. Using quantitative histomorphometry, we measured the middle ear space in 10 chinchillas and found a mean ±SD volume of 2.09 ± 0.08 ml and a mean SD surface area of 14.41 ± 1.48 cm2. To measure the apparent rate constant (Ke) of antibiotic elimination from the middle ear, through the middle ear mucosa, an antibiotic solution was inoculated into the middle ear cavity, and samples were aspirated between 1 and 8 hr later. In normal ears, the mean Ke ±SD for amoxicillin was 0.118 ± 0.013 hr−1, that for a trimethoprim 0.461 ± 0.090 hr−1, and that for sulfamethoxazole 0.265 ± 0.062 hr−1. In ears inoculated with type 7F Streptococcus pneumoniae to induce acute otitis media, the Ke ±SD increased for all three drugs (P < 0.05): amoxicillin to 0.286 ± 0.089 hr−1, trimethoprim to 0.662 ± 0.118 hr−1, and sulfamethoxazole to 0.411 ± 0.056 hr−1. These values demonstrate that amoxicillin had the lowest apparent penetration rate constant of the three antibiotics but the greatest increase from normal to infected mucosa (142{\%}). Trimethoprim had the highest apparent penetration rate constant of the three antibiotics but the smallest increase from normal to infected mucosa (44{\%}), while the sulfamethoxazone apparent penetration rate constant increased from normal to infected mucosa by 55{\%}. The Ke for amoxicillin was the same for inoculation volumes of 0.8 and 1.6 ml (P = 0.557) and the same for sampling intervals of 4 and 8 hr (P = 0.054). All three antimicrobial drug concentration–time curves were log-linear, as predicted by Fick's first law of diffusion. In conclusion, this model overcomes the technical limitations of previous models and permits investigation of the many factors that can influence antibiotic penetration into the middle ear and reduce otitis media treatment efficacy.",
keywords = "amoxicillin, otitis media, pharmacokinetics, sulfamethoxazole, trimethoprim",
author = "Jossart, {Gregg H.} and Erdmann, {Gary R.} and Levitt, {David G} and Peter Kucera and Le, {Chap T} and Juhn, {Steven S} and Giebink, {G. Scott} and Canafax, {Daniel M.}",
year = "1990",
month = "1",
day = "1",
doi = "10.1023/A:1015977603224",
language = "English (US)",
volume = "7",
pages = "1242--1247",
journal = "Pharmaceutical Research",
issn = "0724-8741",
publisher = "Springer New York",
number = "12",

}

TY - JOUR

T1 - An Experimental Model for Measuring Middle Ear Antimicrobial Drug Penetration in Otitis Media

AU - Jossart, Gregg H.

AU - Erdmann, Gary R.

AU - Levitt, David G

AU - Kucera, Peter

AU - Le, Chap T

AU - Juhn, Steven S

AU - Giebink, G. Scott

AU - Canafax, Daniel M.

PY - 1990/1/1

Y1 - 1990/1/1

N2 - Bacteria are an important cause of acute otitis media and successful treatment depends on achieving inhibitory or bacteriacidal antimicrobial drug concentrations in the middle ear. To evaluate further otitis media treatment success and failure, we developed a chinchilla model to study antimicrobial drug penetration through the middle ear mucosa. Using quantitative histomorphometry, we measured the middle ear space in 10 chinchillas and found a mean ±SD volume of 2.09 ± 0.08 ml and a mean SD surface area of 14.41 ± 1.48 cm2. To measure the apparent rate constant (Ke) of antibiotic elimination from the middle ear, through the middle ear mucosa, an antibiotic solution was inoculated into the middle ear cavity, and samples were aspirated between 1 and 8 hr later. In normal ears, the mean Ke ±SD for amoxicillin was 0.118 ± 0.013 hr−1, that for a trimethoprim 0.461 ± 0.090 hr−1, and that for sulfamethoxazole 0.265 ± 0.062 hr−1. In ears inoculated with type 7F Streptococcus pneumoniae to induce acute otitis media, the Ke ±SD increased for all three drugs (P < 0.05): amoxicillin to 0.286 ± 0.089 hr−1, trimethoprim to 0.662 ± 0.118 hr−1, and sulfamethoxazole to 0.411 ± 0.056 hr−1. These values demonstrate that amoxicillin had the lowest apparent penetration rate constant of the three antibiotics but the greatest increase from normal to infected mucosa (142%). Trimethoprim had the highest apparent penetration rate constant of the three antibiotics but the smallest increase from normal to infected mucosa (44%), while the sulfamethoxazone apparent penetration rate constant increased from normal to infected mucosa by 55%. The Ke for amoxicillin was the same for inoculation volumes of 0.8 and 1.6 ml (P = 0.557) and the same for sampling intervals of 4 and 8 hr (P = 0.054). All three antimicrobial drug concentration–time curves were log-linear, as predicted by Fick's first law of diffusion. In conclusion, this model overcomes the technical limitations of previous models and permits investigation of the many factors that can influence antibiotic penetration into the middle ear and reduce otitis media treatment efficacy.

AB - Bacteria are an important cause of acute otitis media and successful treatment depends on achieving inhibitory or bacteriacidal antimicrobial drug concentrations in the middle ear. To evaluate further otitis media treatment success and failure, we developed a chinchilla model to study antimicrobial drug penetration through the middle ear mucosa. Using quantitative histomorphometry, we measured the middle ear space in 10 chinchillas and found a mean ±SD volume of 2.09 ± 0.08 ml and a mean SD surface area of 14.41 ± 1.48 cm2. To measure the apparent rate constant (Ke) of antibiotic elimination from the middle ear, through the middle ear mucosa, an antibiotic solution was inoculated into the middle ear cavity, and samples were aspirated between 1 and 8 hr later. In normal ears, the mean Ke ±SD for amoxicillin was 0.118 ± 0.013 hr−1, that for a trimethoprim 0.461 ± 0.090 hr−1, and that for sulfamethoxazole 0.265 ± 0.062 hr−1. In ears inoculated with type 7F Streptococcus pneumoniae to induce acute otitis media, the Ke ±SD increased for all three drugs (P < 0.05): amoxicillin to 0.286 ± 0.089 hr−1, trimethoprim to 0.662 ± 0.118 hr−1, and sulfamethoxazole to 0.411 ± 0.056 hr−1. These values demonstrate that amoxicillin had the lowest apparent penetration rate constant of the three antibiotics but the greatest increase from normal to infected mucosa (142%). Trimethoprim had the highest apparent penetration rate constant of the three antibiotics but the smallest increase from normal to infected mucosa (44%), while the sulfamethoxazone apparent penetration rate constant increased from normal to infected mucosa by 55%. The Ke for amoxicillin was the same for inoculation volumes of 0.8 and 1.6 ml (P = 0.557) and the same for sampling intervals of 4 and 8 hr (P = 0.054). All three antimicrobial drug concentration–time curves were log-linear, as predicted by Fick's first law of diffusion. In conclusion, this model overcomes the technical limitations of previous models and permits investigation of the many factors that can influence antibiotic penetration into the middle ear and reduce otitis media treatment efficacy.

KW - amoxicillin

KW - otitis media

KW - pharmacokinetics

KW - sulfamethoxazole

KW - trimethoprim

UR - http://www.scopus.com/inward/record.url?scp=0025634403&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025634403&partnerID=8YFLogxK

U2 - 10.1023/A:1015977603224

DO - 10.1023/A:1015977603224

M3 - Article

VL - 7

SP - 1242

EP - 1247

JO - Pharmaceutical Research

JF - Pharmaceutical Research

SN - 0724-8741

IS - 12

ER -