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Comparison of two otitis media models for the study of middle ear antimicrobial pharmacokinetics
D M Canafax1, H Russlie, M J Lovdahl
1Otitis Media Research Center, College of Pharmacy, University of Minnesota, Minneapolis 55455.
Abstract:
We compared two models of acute otitis media that estimate middle ear antimicrobial pharmacokinetics. Using a crossover study design, we compared a systemic drug administration model with a diffusion model we devised that measures the disappearance of antimicrobials from the middle ear. We induced acute otitis media in 14 chinchillas by inoculating S. pneumoniae into the middle ear, then administered 3 antimicrobials: amoxicillin, trimethoprim, and sulfamethoxazole. Next we collected middle ear fluid samples to analyze drug concentrations and compare rate constants for the systemic and diffusion models by analysis of variance. We found that amoxicillin K values were not affected by model testing sequence (p = 0.827) or model type (systemic versus diffusion, p = 0.310), nor were sulfamethoxazole K values: model testing sequence (p = 0.917), model type (p = 0.963). Trimethoprim K values were also not affected by model testing sequence (p = 0/760), but were by model type (p = 0.0001). Trimethoprim elimination from the diffusion model was faster (K = 0.33 +/- 0.17 versus 0.57 +/- 0.09 hr-1) than from the systemic model, although it appears this was caused by sampling before drug distribution into the middle ear was complete. In conclusion, it appears K values derived from either systemic antimicrobial administration or direct middle ear instillation are similar for assessing middle ear antimicrobial pharmacokinetics, and these models can be used interchangeably to study factors affecting otitis media treatment response.
Insights
Two models for estimating middle ear antimicrobial pharmacokinetics in acute otitis media were compared. Results suggest systemic and diffusion models can be used interchangeably for studying otitis media treatment response.
Area of Science:
- Pharmacology
- Microbiology
- Otolaryngology
Background:
- Acute otitis media (AOM) is a common infection requiring effective antimicrobial treatment.
- Accurate pharmacokinetic (PK) models are crucial for optimizing antimicrobial therapy in the middle ear.
- Existing models for middle ear PK may have limitations in their applicability.
Purpose of the Study:
- To compare two distinct models for estimating middle ear antimicrobial pharmacokinetics in AOM.
- To evaluate the interchangeability of a systemic drug administration model and a novel diffusion model for PK assessment.
- To determine if model type influences antimicrobial elimination rate constants.
Main Methods:
- A crossover study design was employed in 14 chinchillas with experimentally induced AOM.
- Three antimicrobials (amoxicillin, trimethoprim, sulfamethoxazole) were administered.
- Middle ear fluid samples were collected to analyze drug concentrations and compare PK rate constants between the systemic and diffusion models using ANOVA.
Main Results:
- Amoxicillin and sulfamethoxazole PK rate constants (K values) were not significantly affected by model type or testing sequence.
- Trimethoprim K values were significantly influenced by model type (p = 0.0001).
- Trimethoprim elimination appeared faster in the diffusion model, potentially due to early sampling before complete drug distribution.
Conclusions:
- Both systemic and diffusion models provide comparable K values for assessing middle ear antimicrobial pharmacokinetics in AOM.
- These models demonstrate interchangeability for investigating factors influencing AOM treatment outcomes.
- The findings support the use of either model for future research into optimizing otitis media therapies.