Canafax D M, Russlie H, Lovdahl M J, Erdmann G R, Le C T, Giebink G S
Otitis Media Research Center, College of Pharmacy, University of Minnesota, Minneapolis 55455.
Pharm Res. 1994 Jun;11(6):855-9. doi: 10.1023/a:1018981808868.
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.
我们比较了两种估算中耳抗菌药物药代动力学的急性中耳炎模型。采用交叉研究设计，我们将一种全身给药模型与我们设计的一种测量抗菌药物从中耳消失情况的扩散模型进行了比较。我们通过将肺炎链球菌接种到14只龙猫的中耳来诱发急性中耳炎，然后给予3种抗菌药物：阿莫西林、甲氧苄啶和磺胺甲恶唑。接下来，我们收集中耳液样本以分析药物浓度，并通过方差分析比较全身模型和扩散模型的速率常数。我们发现阿莫西林的K值不受模型测试顺序（p = 0.827）或模型类型（全身模型与扩散模型，p = 0.310）的影响，磺胺甲恶唑的K值也不受影响：模型测试顺序（p = 0.917），模型类型（p = 0.963）。甲氧苄啶的K值也不受模型测试顺序的影响（p = 0.760），但受模型类型的影响（p = 0.0001）。尽管这似乎是由于在药物完全分布到中耳之前进行采样所致，但甲氧苄啶从扩散模型中的消除速度（K = 0.33±0.17与0.57±0.09 hr-1）比从全身模型中更快。总之，对于评估中耳抗菌药物药代动力学而言，从全身抗菌给药或直接中耳滴注获得的K值似乎相似，并且这些模型可以互换使用以研究影响中耳炎治疗反应的因素。
