An in Vitro Pharmacodynamic Model to Simulate Antibiotic Behavior of Acute Otitis Media with Effusion |
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Authors: | Vance-Bryan Kyle Larson Tom A Garrison Mark W Toscano John P Canafax Daniel M Rotschafer John C |
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Institution: | (1) Section of Clinical Pharmacology, St. Paul-Ramsey Medical Center, St. Paul, and College of Pharmacy, University of Minnesota, Minneapolis, Minnesota, 55455;(2) Veterans Administration Medical Center and College of Pharmacy, University of Minnesota, Minneapolis, Minnesota, 55455;(3) College of Pharmacy, Washington State University, Spokane, Washington;(4) Otitis Media Research Center and College of Pharmacy, University of Minnesota, Minneapolis, Minnesota, 55455;(5) Section of Clinical Pharmacology, St. Paul-Ramsey Medical Center, St. Paul, and College of Pharmacy, University of Minnesota, Minneapolis, Minnesota, 55455;(6) Section of Clinical Pharmacy, St. Paul-Ramsey Medical Center, 640 Jackson Street, St. Paul, Minnesota, 55101 |
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Abstract: | The purpose of this investigation was to develop an in vitro pharmacodynamic model (IVPM) that would simultaneously simulate in vivo serum and middle ear amoxicillin pharmacokinetic characteristics of acute (purulent) otitis media and then utilize the IVPM to assess amoxicillin-mediated killing of a type 7F Streptococcus pneu-moniae (MIC = 0.002 mg/L). The IVPM consisted of a sterile central compartment and a membrane-bound infected peripheral compartment. Peak peripheral compartment amoxicillin concentrations occurred within 2 hr after its introduction into the central compartment and were approximately 30% of peak central compartment concentrations. Amoxicillin elimination from the central compartment was designed to provide a 1-hr t
1/2. Amoxicillin elimination from the peripheral compartment was slower than from the central compartment, with an average half-life of 2.3 hr. Significant concentration-related differences in maximal bacterial kill rates were not detected over the range of amoxicillin concentrations studied (0.26 to 14.6 mg/L). However, at peak central compartment amoxicillin concentrations of 2 mg/L, a lag phase in killing was observed. In general, the in vitro pharmacokinetic data derived from this model compare well with published in vivo data. |
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Keywords: | in vitro pharmacodynamics pharmacokinetics amoxicillin otitis media |
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