This work was performed to develop an experimental animal model for the study of antibiotic drug distribution into @entity2172 ( @entity2172 ) and to evaluate its relevance and significance to the clinical treatment of @entity2346 media (OM). Chinchillas were assigned to normal or infected ear groups after @entity5274 ( @entity5274 ) or direct trans-bullar inoculation with type 3 @entity328 . Following survival surgery to implant microdialysis (MD) probes in the jugular vein and middle ear (ME), @entity115 was given intravenously (iv) as a bolus or infusion. Drug concentrations in blood and @entity2172 were continuously monitored by microdialysis. The measured concentrations were corrected for probe recovery by simultaneous retrodialysis. Multiple @entity2172 and blood sampling was also performed to validate the animal model and MD sampling technique. @entity2348 was successfully induced 3-7 days after the inoculation, whereas the control group gave negative bacterial culture results. The @entity3405 antibiotic, @entity115 , exhibited an elimination half-life of 0.33+/-0.23 h (n = 9) in chinchilla blood, 1.46+/-0.50 h (n = 5) and 1.75+/-0.84 h (n = 4) in @entity2172 of normal and infected ears (p = 0.6), respectively. @entity2172 -to-blood @entity115 concentration ratios at steady state following iv infusion were 0.26+/-0.06 (n = 5) and 0.28+/-0.11 (n = 4) for normal and infected ears (p = 0.7), respectively. MD allows continuous monitoring of drug concentration-time profiles in blood and @entity2172 in an awake chinchilla model. The concentrations measured by MD were validated by direct sampling. The ratio of the area under the curve (AUC) of drug concentration in @entity2172 versus time to that in blood after iv bolus doses was less than unity, as was the steady-state concentration ratio following constant-rate iv infusion, suggesting an active transport mechanism was involved in the efflux of @entity115 from the ME of chinchilla. The results of studies involving infected ears were not significantly different from those in normal ears in terms of @entity115 distribution across the ME mucosal membrane after systemic administration.

Microdialysis studies of the middle ear distribution kinetics of XXXX in the awake chinchilla.

@entity2172 :: ('MESH:D010033', 'Disease') :: ['MEF', 'middle ear fluid'] @entity115 :: ('MESH:D000658', 'Chemical') :: ['amoxicillin'] @entity3405 :: ('CHEBI:35627', 'Chemical') :: ['beta-lactam'] @entity2348 :: ('MESH:D001424', 'Disease') :: ['Bacterial infection'] @entity5274 :: ('MESH:D005184', 'Disease') :: ['ETO', 'Eustachian tube obstruction'] @entity328 :: ('1313', 'Species') :: ['Streptococcus pneumoniae'] @entity2346 :: ('MESH:D010031', 'Disease') :: ['otitis']
@entity115 :: (MESH:D000658,Chemical) :: ['amoxicillin']
