Microdialysis studies of the distribution of antibiotics into chinchilla middle ear fluid.
For conditions such as acute otitis media, in which antibiotic penetration into middle ear fluid (MEF) may be slow or limited, antibiotic plasma levels may not reflect the concentrations at the site of infection that are relevant to clinical outcome. In such cases, a model is needed that will enable prediction of the time course of unbound, pharmacologically active antibiotic levels in MEF. We describe the use of microdialysis as a sampling tool for measurement of unbound antibiotic concentrations in the MEF of the awake, freely moving chinchilla. Results of studies of MEF penetration of the beta-lactam antibiotic, cefdinir, with use of this technique are also described. Preliminary results of studies of the penetration of antibiotics into MEF of the chinchilla appear consistent with clinical findings and suggest that the chinchilla microdialysis model may prove to be a useful tool for predicting antibiotic efficacy in patients.
Sawchuk
Ronald J
RJ
Bioanalytic and Pharmacokinetic Services Laboratory, Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota 55455, USA. sawch001@umn.edu
Cheung
Belinda W Y
BW
Ji
Ping
P
Cartier
Linda L
LL
D000658:Amoxicillin / Q000493:pharmacokinetics / Q000627:therapeutic use; D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000077525:Cefdinir; D002511:Cephalosporins / Q000493:pharmacokinetics / Q000627:therapeutic use; D002682:Chinchilla; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004432:Ear, Middle / Q000378:metabolism* / Q000382:microbiology; D006207:Half-Life; D008826:Microbial Sensitivity Tests; D017551:Microdialysis; D010033:Otitis Media / Q000188:drug therapy / Q000382:microbiology; D013296:Streptococcus pneumoniae
D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D000658:Amoxicillin; D000077525:Cefdinir